The Lundbeck Foundation 2010│11

THE LUNDBECK FOUNDATION 2010 11

nspires and recognizes talent search prizes and fellowships esearch of the highest quality neuroscience and psychiatry nationalization by specifically ation between leading Danish nternational research groups THE RECIPIENTS OF THE LUNDBECK FOUNDATION’S TALENT PRIZE 2010

The Lundbeck Foundation is a Danishbased commercial foundation that is striving to significantly improve the population’s health and wellbeing by: • supporting independent Danish research, primarily within biomedicine and the natural sciences, at the highest level, and promoting its internationalization • creating shareholder value in the Lundbeck Group and other inter nationally renowned companies, and helping them become world leaders in their respective fields

CONTENTS

THE LUNDBECK FOUNDATION’S ACTIVITIES AND RESULTS IN 2010

2

MANAGEMENT AND CORPORATE GOVERNANCE

5

LUNDBECK FOUNDATION GRANTS 2010

6

GRANT STRATEGY

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THEME – talenTS

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LUNDBECK FOUNDATION JUNIOR GROUP LEADER FELLOWSHIPS 2010

20

LUNDBECK FOUNDATION GRANTS OF EXELLENCE 2010

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THE BRAIN PRIZE – DENMARK'S FIRST MAJOR INTERNATIONAL RESEARCH PRIZE

30

METHOD, MOTIVATION AND BALLOON DANCE

33

LUNDBECKFOND INVEST A/S

36

H. LUNDBECK A/S

39

ALK-ABELLÓ A/S

40

FALCK A/S

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LUNDBECKFOND VENTURES

42

RESULTS 2010

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THE LUNDBECK FOUNDATION’S ACTIVITIES AND RESULTS IN 2010 The Lundbeck Foundation is a Danish-based commercial foundation which holds stakes in a number of Danish internationally operating companies. The return made on the Foundation’s commercial activities is used to fund Danish research within the biomedical and natural sciences. The Foundation’s grants are estimated to fund around 500 researchers at Danish universities and university hospitals and, to an increasing degree, Danish researchers working abroad.

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From the Award ceremony for the Foundations prize for Young Researchers (from left) Mogens Bundgaard-Nielsen, Jørgen Huno Rasmussen, Lars Juhl Jensen, Nils Axelsen and Steen Hemmingsen

The Foundation was established in 1954 by Grete Lundbeck, widow of the founder of the pharmaceutical company H. Lundbeck A/S. Before H. Lundbeck A/S was listed on the stock exchange in 1999, the Foundation’s assets consisted primarily of shares in the company.

In recent years, yields from H. Lundbeck A/S and returns from the Foundation’s other investments have facilitated a significant expansion of both commercial and funding activities. In terms of market value, the Foundation’s assets at the end of 2010 amounted to a total of DKK 28.6 billion, of which DKK 14.6 billion (51 pct.) consists of shares in H. Lundbeck A/S. Material growth in the Foundation’s free assets over the past years has enabled the Foundation to expand its commercial activities as an alternative to passive asset management. This strengthens both the Foundation’s grantmaking capacity going forward and the capital base for its subsidiaries.

COMMERCIAL ACTIVITIES

The commercial activities are conducted through the wholly owned investment and holding company Lundbeckfond Invest A/S. It holds substantial interests in Danish healthcare companies and includes an entity for investments in life science companies, Lundbeckfond Ventures.

On 14 December 2010, the Lundbeck Foundation entered into an agreement with the majority shareholder in Falck A/S that Lundbeckfond Invest A/S would acquire 36 pct. of the equity in the Falck Group. The formal transfer of shares took place on 14 January 2011.

The Falck Group is a well-run company with Danish roots, working in vital areas of society including the health sector. The Falck Group has expanded its activities in recent years and now operates in 25 countries and has approx. 19,000 employees. As of the start of 2011, the Falck Group is an associate company of Lundbeckfond Invest A/S, which also continues to hold 70 pct. of the equity in H. Lundbeck A/S and 38 pct. (66 pct. of the votes) in ALK-Abelló A/S, the world’s largest producer of allergy vaccines. H. Lundbeck A/S and ALK-Abelló A/S are listed on Nasdaq OMX Copenhagen. Both companies improved their financial performance in 2010. H. Lundbeck A/S achieved its best result ever, and the company's productivity was improved, increasing its robustness, despite the fact that some of its patents will soon expire. The stake owned by the Foundation/Lundbeckfond Invest A/S in both listed subsidiaries remained unchanged in 2010.

In the life science sphere, Lundbeckfond Invest A/S backed the proposal in 2010 of an increase in equity of DKK 475 million in the associated company LifeCycle Pharma A/S, which is also listed on Nasdaq OMX Copenhagen. The infusion of capital is intended to fund the final phase 3 trials in the USA of its product for use in organ transplants. Following the increase, Lundbeckfond Invest A/S now owns 31 pct. of the equity in LifeCycle Pharma A/S. Lundbeckfond Ventures, which was established at the end of 2009, made a positive start in 2010. After examining numerous proposals, it invested in four new life science companies.

GRANTS

In addition to growth in the commercial activities, the Foundation’s funding activities also continued to grow in 2010. The objective is to boost free Danish research at the highest level, primarily within biomedical and natural sciences, and to promote the internationalization of Danish research. Grants amounted to DKK 384 million, compared with DKK 340 million in 2009. In 2010, the Foundation continued to fund research within biomedical and natural sciences, via applications made through its online application system followed by independent peer reviews by international scientific advisory committees, on which a majority of the members are independent of the Lundbeck Foundation's administration and board. Of the grants allocated in 2010, DKK 100 million went to seven fellowships for heads of research teams, to enable them to set up or expand their own teams at Danish universities and university hospitals.

In 2010, the Lundbeck Foundation made a donation to establish the “Grete Lundbeck European Brain Research Foundation” as part of its strategic focus on neuroscience. The purpose of the new foundation is to honour outstanding European brain research by awarding a major, personal research prize. In addition to honouring and highlighting excellence in research, the prize will also provide a boost to Danish neuroscience through an extensive outreach programme in Denmark.

The first €1 million “Brain Prize" was awarded on 2 May 2011 (see separate article).

In recent years, private foundations, including the Lundbeck Foundation, have increased their support to research at the Danish universities.

Denmark is one of the countries in which the proportion of funding for research at state universities provided by private foundations is the highest. In this context, the Lundbeck Foundation welcomes the

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The recipients of 'The Brain Prize': Tamás Freund, Györgyi Buzaki and Péter Somogyi, with the President of the European Research Council Helga Nowotny and the Danish minister of Interior and Health, Bertel Haarder.

continued close interaction between the Foundation, the universities and the Ministry of Science. A good example of this was Parliament’s adoption of a matching fund, through which the government matches donations from private foundations to Danish universities with a certain percentage of co-funding. This is expected to serve as a further incentive for the universities to attract private funding.

FINANCIAL PERFORMANCE

The Lundbeck Foundation made a profit of DKK 2,703 million in 2010, the second best in its history. DKK 2,587 million of this stems from the commercial activities of the wholly owned investment and holding company Lundbeckfond Invest A/S. The non-commercial activities of the Foundation itself made a profit of DKK 113 million.

The DKK 384 million awarded in grants was therefore partially funded by a dividend paid to the Foundation of DKK 400 million from Lundbeckfond Invest A/S. The financial markets also performed reasonably in 2010, albeit with major fluctuations throughout the year. Lundbeckfond Invest A/S achieved a return on its portfolio investments of approx. 11 pct., corresponding to DKK 1,060 million, which is considered satisfactory.

OTHER MATTERS

In May, elections were held for employee representatives to the Board.

Project manager Ken Liljegren and operator Kim Klitgaard from H. Lundbeck A/S were newly elected and senior researcher Peter Adler Würtzen of ALK-Abelló A/S was re-elected.

When it convened after the annual meeting in May 2010, the Board re-appointed civil engineer Mogens Bundgaard-Nielsen as the chairman and appointed professor Mikael Rørth as vice-chairman. At the annual meeting on 30 May 2011, Steen Hemmingsen will step down as managing director of the Foundation and of Lundbeckfond Invest A/S after more than 11 years of service. The new managing director will be Christian Dyvig. Steen Hemmingsen will retain links to the Foundation as an advisor with special responsibilities.

The Lundbeck Foundation would like to avail itself of this opportunity to thank its employees, managers of subsidiaries and partners on evaluation committees, at universities and in the ministries of health and science for all their positive input in 2010.

Mogens Bundgaard-Nielsen Chairman of the Board of Trustees

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Steen Hemmingsen Managing Director

MANAGEMENT AND CORPORATE GOVERNANCE The Lundbeck Foundation is managed by a Board of Trustees consisting of six members elected among themselves and three members elected by employees of the two companies H. Lundbeck A/S and ALK-Abelló A/S. The Board appoints the Foundation’s managing director, who also serves as the managing director of Lundbeckfond Invest A/S. Election of the Trustees takes place at the annual general meeting. The members of the board, who are elected by the employees of the two companies, cannot participate in the election of the Trustees.

Members of the Board of Trustees are elected for one year, i.e. for the period until the end of the next annual general meeting. Re-election can take place. However, election or re-election of someone who has been a member of the board for more than a total of 12 years or has turned 75 years cannot take place. The rule in the previous sentence can be dispensed of in case it is deemed necessary/desirable.

The Board of Trustees elects a chairman and deputy chairman immediately after the AGM. Lundbeckfond Invest A/S has the same board and managing director as the Foundation. The chairman of the Foundation’s Board of Trustees is also chairman of Lundbeckfond Invest A/S’ board but, if it is deemed practical, there may be different deputy chairs on the two boards.

The Lundbeck Foundation (and Lundbeckfond Invest A/S) holds a minimum of four board meetings a year, plus a two-day seminar to discuss strategy, etc. The Trustees also visit the Foundation’s research centres and attend contact meetings with Danish universities where the Foundation has interests.

There are written rules addressing potential conflicts of interest in relation to grant-making, as well as rules governing Trustees’ and others’ use of these allocations.

The board is subject to self-evaluation in the form of dialogue between the chair and individual members, followed by discussions involving the whole board. In the companies controlled by the Foundation, a minimum of half of the members elected at the AGM, usually including the chair, must be independent of the main shareholder (the Foundation). The board is not involved in the day-to-day operations of the companies but does seek to exert influence via representation on the companies’ boards of directors and at their AGMs, especially concerning strategy. However, the Foundation considers it important that the companies have qualified and dynamic boards capable of taking the companies forward and providing shareholder value. The chairman of the Foundation is not eligible to sit on the company boards.

The Lundbeck Foundation (and Lundbeckfond Invest A/S), its Board of Trustees and senior officers only dispose concerning purchase and sale of shares in H. Lundbeck A/S and ALK-Abelló A/S in the special periods designated by the respective board of directors in these companies in connection with announcements to the stock market.

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THE LUNDBECK FOUNDATION WITH ITS GRANT ACTIVITIES • Supports independent research of the highest quality with special focus on neuroscience and psychiatry.

• Promotes internationalization by specifically supporting collaboration between leading Danish and international research groups.

• Motivates, inspires and recognizes talent by awarding research prizes and fellowships.

Divides grants into: • Project support for independent biomedical and natural science research, awarded through open competition.

• Strategic areas with a special focus on groundbreaking research, as identified by the Foundation's Board of Trustees, and implemented via specific programmes.

GRANTS 2010

NUMBER OF GRANTS

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BASIC RESEARCH 66%

APPLIED RESEARCH 30%

DEVELOPMENT 4%

”In 2011, the Foundation expects to provide approximately DKK 400 million in funding within the same strategic framework as defined in 2010.”

In 2010, the Lundbeck Foundation provided 319 research grants, amounting to total funding of DKK 384 million. The Foundation received 1,148 funding applications, amounting to a total of DKK 2.2 billion.

The Foundation provided DKK 271 million in funding for basic research, DKK 78 million for applied research and DKK 35 million for research that also involves development work.

High-quality advice is essential when selecting projects to be funded.

Applications are assessed either by one of the Foundation’s two standing committees, covering biomedical and natural sciences, or by ad hoc panels consisting of international experts. In both cases, the majority of the assessors will be independent of the Foundation.

STRATEGIC FRAMEWORK FOR THE FOUNDATION’S FUNDING ACTIVITIES

The strategic framework for the Foundation’s funding activities is depicted on the opposite page.

In 2011, the Foundation expects to provide approximately DKK 400 million in funding within the same strategic framework as defined in 2010.

The overriding criterion for the Foundation’s research funding is that its grants must make a difference.

The Foundation supports free and independent research of the highest international caliber, with particular focus on research in neuroscience and psychiatry, as described in the funding strategy at the end of this article.

By utilising a variety of instruments, the Foundation expects that its grants will support the development of talent and promote the internationalization of Danish research.

FOCUS ON TALENT

The Lundbeck Foundation aims to “motivate, inspire and recognise research talent”, e.g. by awarding honorary prizes and fellowships as per the strategic frameworks for its grants.

Many different characteristics and competences are necessary in order to develop an outstanding research career and contribute to scientific

breakthroughs. However, the environment surrounding the researcher must also be special in order to secure for him or her the best possible development opportunities, both during “training” (as students, PhD students and young postdocs) and subsequently, when they establish a more independent profile as a specialist in a particular field. In recent years, there has been an increasing focus on talent in research. This applies both to identifying exceptionally talented pupils, students and researchers, and to cultivating, retaining and inspiring talent by means of financial support or particularly favourable working conditions.

Talent is now on the agenda in working groups, book publications, and discussions about primary and lower secondary school, as well as in debates on how best to prioritise the resources available to research funding, which are invariably limited.

The theme article in this year’s annual report focuses on talent. We asked three prominent “talent-savvy” Danes to talk about talent and how to nurture it. Furthermore seven of the talents who received funding from the Lundbeck Foundation in 2010 are introduced, namely the five Junior Group Leaders, the recipient of the Young Scientist Prize and one of the three recipients of the Foundation’s Talent Prize.

INSTRUMENTS

Pursuant to its strategic framework for donations and its funding strategy, the Lundbeck Foundation used a variety of instruments to support free and independent Danish research in 2010.

Project funding is allocated to biomedical- and natural-science projects that fall within the framework of the strategy. Applications are invited three times a year for biomedical science projects and once a year for natural science projects. In 2010, biomedical science project grants totalling DKK 184 million were awarded to 155 projects. A total of 22 natural science projects received DKK 25 million. Applicants for project funding categorise their research as basic research, applied (clinical) research or development work, and state their specialisation.

The Foundation uses this information for statistical analysis of applications and grants within the various specialisations. The split between biomedical science and natural science is found on the next page. All grants are listed on the Foundation’s website: www.lundbeckfonden.dk.

JUNIOR GROUP LEADER FELLOWSHIPS

Since 2007, the Foundation has awarded a total of 15 Junior Group Leader Fellowships (each worth DKK 10 million) to particularly promising young researchers who are about to start their own research

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NUMBER OF

35

PROJECT GRANTS FOR BIOMEDICAL SCIENCE,

30

BASIC RESEARCH, 2010

25

20

15

10

5

0 NEUROSCIENCE

NUMBER OF PROJECT GRANTS FOR BIOMEDICAL SCIENCE, CLINICAL RESEARCH

BIOCHEMISTRY

CANCER CELL AND RESEARCH MOLECULAR BIOLOGY

PHARMACOLOGY

PHYSIOLOGY

GENETICS

IMMUNOLOGY

MICRO- OTHER BASIC BIOLOGY RESEARCH

18 16 14

(APPLIED RESEARCH) AND DEVELOPMENT WORK, 2010

12 10 8 6 4 2 0 PUBLIC-HEALTH MEDICINE

NUMBER OF

INFECTION MEDICINE, ALLERGOLOGY, MEDICAL GASTROENTEROLOGY, DERMATOLOGY, VENEROLOGY AND CARDIOLOGY

ANAESTHESIOLOGY AND PAEDIATRICS

CLINICAL BIOCHEMISTRY, PHARMACOLOGY, GENETICS AND IMMUNOLOGY

NEPHROLOGY AND ENDOCRINOLOGY

NEUROLOGY, NEUROSURGERY, PSYCHIATRY AND PHYSIOLOGY

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PROJECT GRANTS FOR THE NATURAL SCIENCES,

10

2010 8

6

4

2

0 BIOCHEMISTRY

10

MATHEMATICS

PHYSICS AND BIOPHYSICS

CHEMISTRY

Recipients of the Lundbeck Foundations' Junior Group Leader Fellowships 2010: Christian Adam Olsen, Jes Kristian Jørgensen, Thomas P. Gilbert, Blagoy Blagoev and Michael Pittelkow (from left).

teams at Danish universities. A call is announced in Danish and international research journals once a year. The Foundation has noted growing interest in this instrument, and receives many applications from very highly qualified young researchers wishing to establish themselves and their research teams in a good Danish research environment. 2010 was no exception. The Foundation received a total of 48 applications, five of which were successful. The Lundbeck Foundation Junior Group Leader Fellowships are interviewed in the annual report.

The five recipients are:

des. It is known that they affect the enzymes that regulate cell division, and that this in turn affects the survival chances of cancer cells, since treatment with these substances causes the cells to commit suicide.

Taking their starting point in these natural substances, Christian Olsen’s group will produce different variants of them in the laboratory, each of which will be capable of specifically targeting a single enzyme.

The long-term goal is to produce drugs that – with maximum precision and minimum side-effects – can be used to treat certain cancers.

Michael Pittelkow, Associate Professor, Department of Chemistry, University of Copenhagen. The research project's title is "Dynamic Combinatorial Chemistry – Supramolecular Chemistry in Water."

The objective of Michael Pittelkow’s research is to develop research tools that will help generate a detailed understanding of how molecules involved in chemical reactions find the most suitable binding partners.

The experiments are set up in such a way that the molecules themselves find the best binding partners, while the researchers' role is to identify the experimental conditions that provide the molecules with optimal reaction conditions. In the longer term, the results of experiments like this may be used to develop for instance medicines and explosives detection markers, and to identify various carbohydrates.

Blagoy Blagoev, Associate Professor at the Department of Biochemistry and Molecular Biology, University of Southern Denmark. The research project’s title is "In-depth Investigation of the Processes Underlying Human Embryonic Stem Cells’ Maintenance and Differentiation by Advanced Quantitative Proteomics". Blagoy Blagoev’s research focuses on the control mechanisms that govern the development of human cells from stem cells to mature and specialised cells. Stem cells have great potential in regenerative medicine, the objective of which is to rebuild or replace damaged tissue. Greater knowledge is needed of the complex and dynamic systems that regulate stem cells’ biology in order to improve their practical medical applications. The research team uses a method of analysis called quantitative mass spectrometry to obtain detailed information about the factors that regulate the maintenance of a base population of stem cells, and the factors that cause the differentiation of stem cells into specialised cells.

Jes Kristian Jørgensen, Associate Professor, the Niels Bohr Institute, University of Copenhagen. The research project’s title is "The Earliest Phases of Circumstellar Discs". Jes Jørgensen conducts research into the origins of solar systems similar to our own. Stars like our Sun are formed in clouds of dust and gas. The clouds condense and over a period of a few hundred thousand years they collapse to form a young star (a protostar). The remnants of the dust and gas cloud circulate in a disc around the star, and planets may form from these residues. Jes Jørgensen and his team are able to measure the exact chemical composition of the gas around young stars, and from these readings calculate whether, in addition to water, more complex organic molecules are also present. The discs’ physical properties can be described in greater detail, and the observations may help to determine how the earliest stages of the formation of stars and planets relate to how our own solar system looks today.

Christian Adam Olsen, Associate Professor at DTU Chemistry, Technical University of Denmark. The research project’s title is "Gene Regulation with Small Molecule Epigenetic Modulators". Christian Olsen's research focuses on natural substances known as cyclic pepti-

Thomas Gilbert, Associate Professor at the Centre for GeoGenetics, University of Copenhagen. The title of the project's is "Pathogen Paleo-genomics: Looking at the genetic history of pathogens to better our understanding of their origin, evolution, spread and control". The project focuses on the viruses behind three different diseases that affect three different species on Earth; the hepatitis C virus, which gives people contagious hepatitis; a herpes viral disease that affects large sea turtles and prevents them from eating and swimming; and finally the stubborn virus that causes potato plague and is quick to develop resistance to pesticides. By looking at the genetic history of various types of virus and by analysing virus gene sequences from historical material, the research group will examine the three different diseases’ histories and spreading.

GRANTS OF EXCELLENCE

In recent years, a large number of Centres of Excellence have been established in Denmark, including 15 by the Lundbeck Foundation

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Recipients of the Lundbeck Foundations' Grants of Excellence 2010, Professor Hartwig Siebner (left) and Professor Lars Edvinsson.

in the period 2005–2009. In 2009, the Board did not invite applications for Centres of Excellence in 2010, as it was concluded that large grants would instead be more effective when awarded to particularly excellent researchers who manage their own small research teams.

Consequently, it was therefore decided that the Foundation in addition to granting five Junior Group Leader Fellowships, invited applications for two Grants of Excellence in neuroscience of DKK 25 million each over five years. After international evaluation of the applications and interviews with selected candidates, it was decided that the Grants of Excellence would be awarded to two professors at the University of Copenhagen: Hartwig Siebner (Hvidovre Hospital) and Lars Edvinsson (Glostrup Hospital) to continue and intensify their excellent neuroscience research.

be blocked in order to improve the brain’s blood flow and reduce the extent of the brain damage following a stroke.

INTERNATIONALIZATION

In addition to the brief description of the recipients and their projects below, further information is available in special articles in the annual report.

The internationalization of Danish research is an important priority for the Lundbeck Foundation. Danish researchers who go abroad and work in international environments build up knowledge, expertise and networks that benefit them and their research, whether they choose to stay abroad or return to Denmark and continue their research career here. Research at Danish universities and university hospitals has benefited greatly from researchers who return with new ideas and knowledge of new methods – as well as good networks with host environments abroad. Researchers from other countries are also increasingly contributing to the internationalization of Danish research. The Foundation funds projects that involve a large number of Danish researchers who want to travel to conduct research, as well as projects in Denmark involving researchers, PhD students or postdocs from abroad.

Professor Hartwig Siebner, Danish Research Centre for Magnetic Resonance (DRCMR), Copenhagen University Hospital, Hvidovre.

Grant of Excellence – project title: "Mapping, Modulation & Modelling the Control of Actions (ContAct)". The project aims to map how the brain controls our actions. The research plans also include studies of which centres in the brain are activated, and in what order, when executing movements. The team will also study disruption in the brain’s processing of information, e.g. as a result of a stroke. With magnetic stimulation, it is possible to inhibit or increase activity in specific areas of the cerebral cortex. When the motor cerebral cortex is stimulated directly, movement is triggered without conscious control.

In 2010, the Foundation launched a new instrument, Visiting Professorships. The intention is to make it possible for Danish biomedical research environment to apply for funds to pay and accommodate a scientist from abroad at professor level for up to six months. It often represents something of a challenge to quickly raise funds for visiting scientists, and as the most prominent of them often are highly sought after by research environments all over the world, the Foundation has established an assessment procedure that provides applicants with an answer within 3-4 weeks. The hope is that an instrument of this kind, with a short response time, will further internationalize Danish biomedical research by providing visits by colleagues with specialist skills.

Professor Lars Edvinsson, Department of Clinical Experimental Research, Glostrup Research Institute, Copenhagen University Hospital. Grant of Excellence – project title: "Targeting Cerebrovascular Signal Transduction in Stroke Treatment". Lars Edvinsson conducts research into the brain’s blood flow and is behind a breakthrough in the understanding of stroke. His research has led to a new understanding of what may cause brain damage in the period immediately after a stroke. Raised levels of certain receptors have been found in the brain’s blood vessels, which reduce blood flow in the affected area of the brain in response to damage to the brain’s blood vessels and nerve cells. The reduced blood flow leads to brain cells in the region dying due to lack of oxygen. The project studies how the signals from the receptors can

RESEARCH PRIZES

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The Lundbeck Foundation awards annual prizes to particularly talented researchers.

Candidates are nominated by their supervisors or senior colleagues.

It is not possible to apply for these prizes. The Foundation’s external assessors review the nominations and present their conclusions to the prize committee, which then issues a recommendation to the Board.

In 2010, three talent prizes were awarded to particularly promising young scientists under 30, while the Foundation’s Research Prize for Young Scientists went to a particularly promising researcher under 40.

Recipients of the Lundbeck Foundations' Talent Prize 2010, Tomasz Wojdacz, Lotte Holmegaard and Søren Dinesen Østergaard (from left).

The three talent award recipients, each of whom received DKK 100,000 as a personal acknowledgement, are: Lotte Holmegaard, MSc, PhD from Aarhus University, Department of Chemistry. Lotte Holmegaard received the award for her work in controlling the position of molecules using powerful laser beams in electric fields. By keeping the molecules in fixed positions, Lotte Holmegaard will be able to film changes to their structure during a chemical reaction.

THE BRAIN PRIZE

In 2010 the Lundbeck Foundation established the Grete Lundbeck European Brain Research Foundation. The Foundation aims to raise awareness of neuroscience research in Denmark, to promote the internationalization of Danish neuroscience, and to support and reward excellence in European neuroscience. The Brain Prize of €1 million will go to one or more researchers or research teams in recognition of particularly significant work. The annual report contains an article about the first award, written by chief physician, MD Nils Axelsen, chairman of the new prize foundation.

Søren Dinesen Østergaard, M.B., PhD student at Aalborg University Unit for Psychiatric Research. Søren Dinesen Østergaard received the award for his work on the diagnosis and treatment of patients with depression in general practice. The research focuses on patient groups at particular risk of developing severe depression with psychotic symptoms such as hallucinations and delusions. The objective is that the research will contribute to improved diagnosis and more targeted treatment of different groups of patients suffering from depression.

Tomasz Wojdacz, biotechnologist from the University of Silesia, Poland, and PhD from Aarhus University, Department of Health Sciences. Tomasz Wojdacz received the prize for his methodological research that deals with the determination of the amount and location of specific chemical groups, methyl groups, on DNA molecules.

Changes in the groups’ location pattern are expected to be used as biomarkers for individual diagnosis and treatment, e.g. cancer, psychiatric conditions and age-related illnesses.

The Lundbeck Foundation Research Prize for Young Scientists 2010 went to Professor Lars Juhl Jensen, University of Copenhagen, Novo Nordisk Foundation Centre for Protein Research. The prize is an honorary personal award of DKK 300,000. Lars Juhl Jensen’s research field is bioinformatics. He received the award in recognition of his outstanding contribution to the understanding of complex biological systems, including cell cycles and their regulation. His research has led to the discovery of the principles underlying the regulation of the cells’ “molecular machines” (protein complexes), as well as the development of several analytical tools, which are used by thousands of researchers worldwide. Lars Juhl Jensen has also helped to further develop research processes, including the use of various online services for the rapid dissemination of research results. His research has been published in leading scientific journals and has had great international impact.

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GRANT STRATEGY The Lundbeck Foundation, through the awarding of grants, aims to strengthen Danish research of the highest quality in biomedicine and natural sciences.

Neuroscience is a core area for the Foundation, but projects within other areas are also supported. However, the Foundation has reservations in areas where other Danish foundations and institutions have special interests and obligations.

RESEARCH IN EPIDEMIOLOGY AND DISEASE PREVENTION

TRANSLATIONAL AND CLINICAL BIOMEDICAL RESEARCH

BASIC RESEARCH INCLUDING PHYSICS AND CHEMISTRY. RESEARCH INTO DISEASE MECHANISMS

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NATURAL SCIENCES COMMITTEE (FROM LEFT) JES ØSTERGAARD, CHAIRMAN, CIVIL ENGINEER, LUNDBECK FOUNDATION BOARD MEMBER BJÖRN LINDMAN, PROFESSOR, PH.D. KNUT CONRADSEN, PROFESSOR, DR. PHIL. TORKILD ANDERSEN, PROFESSOR, DR. PHIL.

BIOMEDICAL SCIENCES COMMITTEE (FROM LEFT) MIKAEL RØRTH, CHAIRMAN, PROFESSOR, M.D., LUNDBECK FOUNDATION BOARD MEMBER OLE PETTER OTTERSEN, PROFESSOR, M.D. OLE WILLIAM PETERSEN, PROFESSOR, M.D. BERTIL HAMBERGER, PROFESSOR, M.D. EDVARD SMITH, PROFESSOR, M.D. JØRGEN FRØKIÆR, PROFESSOR, M.D. ANDERS BJØRKLUND, PROFESSOR, M.D. NILS AXELSEN, CHIEF PHYSICIAN, M.D., LUNDBECK FOUNDATION BOARD MEMBER

INSTRUMENTS

APPLIED RESEARCH AND PREVENTION RESEARCH

The Lundbeck Foundation supports high-quality research in biomedicine and natural sciences carried out in Denmark or by Danish researchers abroad through a number of instruments:

Within these areas, there will be more emphasis on projects with immediate or expected future relevance for or impact on neuroscience.

APPLICATIONS CAN BE SUBMITTED FOR

• Research projects • Visiting researchers and travel stipends • Junior Group Leader Fellowships RESEARCH PRIZES

Projects outside the fields of biomedicine and natural sciences are only funded to a very limited degree, and it is normally a precondition that they are scientific in nature.

The Lundbeck Fundation is committed to maintain and exploit the opportunities and freedom of a private foundation as being independent of special interests and public institutions.

The prizes cannot be applied for but nominations are accepted from leading scientists at Danish universities.

• Talent Prizes • Research Prizes for Young Scientists ASSESSMENT OF APPLICATIONS AND NOMINATIONS

All project applications are assessed by one of the Foundation’s two International Scientific Advisory Committees, i.e. biomedical sciences or natural sciences.

Assessment of other applications to the Foundation takes place in collaboration with independent external experts according to generally accepted standards of impartiality and competence.

BIOMEDICAL SCIENCES

The Lundbeck Foundation divides biomedical research into three levels: basic research, applied (translational / clinical) research and research within epidemiology and prevention of disease.

Basic research is generally perceived as research into disease mechanisms, and consequently focus on a particular topic is not required for applications within this area.

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Talent: Special – innate or learned – ability or gift in a particular sphere

Every year, the Lundbeck Foundation awards an annual honorary prize of DKK 100,000 to talented researchers under the age of 30 who conduct particularly promising research within the biomedical and natural science and a Research Prize for Young Scientists under the age of 40 of DKK 300.000. Nominations are submitted by their mentors, usually senior researchers at a university or college of higher education.

Researchers cannot apply for the prizes themselves.

“We need talent in Denmark, and it is important that talented people are identified and encouraged early on so that they continue down the research path,” says Anne-Marie Engel, Director of Research at the Lundbeck Foundation.

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THEME TALENTS

Talent Manager Hanne Hautop, Rector Stefan Hermann and Professor Jens Christian Djurhuus discuss the topic of nurturing talent in articles on the next few pages. Two recipients of the Foundation’s prizes also talk about their work and what it has meant to receive the prize.

”There needs to be an environment that fosters enthusiasm, which is often the first sign of talent.”

Anne-Marie Engel

The recipients are not selected on the basis of their academic qualities alone.

TALENT ON THE AGENDA

It used to be almost forbidden to talk about particularly gifted children. Now, talent is high up the education agenda. A working group set up by the Minister of Education looked into how the system approached working with talent in the past – and at how to proceed in the future.

“A lot of initiatives have been launched, especially in the sciences, and people are positive about talent work, even in elementary school,” says the chair of the group, Rector Stefan Hermann of Metropolitan University College.

“We also look at whether they are capable of posing original questions, challenging their older colleagues. Both academic standards and attitude towards conducting research play a role. You have to be good at both to be awarded the prizes,” she points out.

Anne-Marie Engel is convinced that Denmark has plenty of potential talent, but thinks it needs to be nurtured in order to bloom.

“There needs to be an environment that encourages enthusiasm, which is often the first sign of talent. Talent doesn’t evolve in isolation and of its own accord – it’s important that teachers recognise excellence and new ways of looking at the world. Teachers who reject a pupil’s suggestion for a solution because they did not consider it an option themselves, run the risk of ending up in a situation where they are putting out small flames of inspiration from enthusiastic pupils.”

SCIENCE IN THE SHADE

”Talent is more malleable than we used to believe.

It is clearly also a product of nurture, but it has to be worked on.”

Anne-Marie Engel also wonders why humanities overshadow the natural sciences in the Danish primary and lower secondary school system.

Stefan Hermann

“Nobody would dream of opting out reading, but in the upper secondary school you can downgrade math to virtually nothing. Why do cultural subjects have preference? Niels Steensen, one of Denmark’s greatest natural scientists, was a theologian, but that didn’t stop him conducting research into anatomy and geology. To develop, a society needs good researchers, not least within the natural sciences,” she adds.

“Students thrive on it – their involvement increases and their academic results improve. On top of that, there is a considerable knock-on effect on classmates. The best pupils also help motivate their less talented classmates, who are proud of those who excel,” Stefan Hermann explains.

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The Maersk Mc-Kinney Møller Science Centre is beautifully located at the bank of Sorø Lake.

The centre was inaugurated in August 2009 and houses the Danish national talent management program for science.

Young talents at camp are also challenged with physical activities, e.g. with GPS based orienteering races. Half of the team are running around as agents in the academy garden, while the other half are sitting at computers in the control room directing them.

Every year Science Talents organizes a large Lego robot competition in collaboration with First Lego League. Last year 112 children participated in the competition where they had to get homebuilt Lego robots to find their way (without remote control) through a track and to solve various tasks.

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PROCESSING TALENT

THEME TALENTS

The working group defines a talented youngster as “a person who is good at something and has the potential to become one of the best if properly stimulated”. The stimulation part is significant because it does away with the perception of talent as something that always wins through, irrespective of external circumstances.

“The dyslexic student may be very good at geometry, but his or her talent has to be seen and acknowledged before it can be nurtured. Talent is more malleable than we used to believe. It is clearly also a product of nurture, but it has to be worked on.”

STARTS IN CHILDHOOD

“If talent is to flourish, teachers need to be better trained to handle it,” Stefan Hermann stresses.

“As things stand, teachers usually produce their own material for specially talented pupils. There’s nowhere for them to source it. Our current school system has been good at differentiating downwards – we make provision for the kids who lack something, but not for those who have that something extra. Different subjects deal with talent differently too. Talent work needs to be based on strong academic foundations in the teaching staff, especially in primary and lower secondary schools.”

THREAT TO STATE SCHOOLS

“This applies especially to natural science subjects, which are not well served in state primary and lower secondary schools. Children are inquisitive and marvel at nature. At first, they want to learn, but a lot of them lose interest as they grow up. A considerable number of children and young people out there fail to thrive because they lack challenges.

If it continues, a lot of talent will be wasted. It will also exacerbate divisions and inequality, because parents will opt out of the state primary and lower secondary school system in favour of private schools that support their children’s abilities and interests in specific disciplines as much as possible.”

they encounter in their day-to-day lives, but it helps to keep up and boost their interest,” Hanne Hautop explains.

As head of Denmark’s first centre for nurturing talent, her task is to make sure that talented youngsters with an interest in science are identified and encouraged, preferably at an early age. The Centre also runs activities for teachers, who learn how to recognise and nurture talent.

RESOURCES FOR THE BRIGHTEST

“In Denmark, the tradition has always been that the school system allocates extra resources to the weak – those who have difficulties with reading and math or who lack social skills. No special provisions are made for the brightest. They are given little or no homework, and they aren’t challenged in a manner commensurate with their abilities. You don’t become the best in the world at something if you don’t practise!

A lack of challenges smothers talent before it has a chance to breathe.

There’s a group of youngsters out there who might contemplate dropping the subjects they are best at because they are bored,” she adds.

Stefan Hermann holds a Master in Political Science. As Rector of Metropolitan University College, his responsibilities include training the schoolteachers of the future.

CHALLENGE NURTURES TALENT

Even the most ardent interest in chemistry, mathematics, biology or other scientific areas will evaporate unless stimulated early on. Talent Manager Hanne Hautop and her colleagues at Science Talents, part of the Maersk McKinney Møller Science Centre in Sorø, aim to do something about that. Their organisation focuses on nurturing talent in the natural sciences.

At the centre, selected youngsters age 12–20 spend a few days wrestling with bigger and more complex problems than they are accustomed to addressing in the school system. The setting is ideal – Science Talents’ facilities would make many universities green with envy. In the company of like-minded peers, youngsters discover that there are people all over the country who are just as hooked on science as they are.

IT’S OK TO LIKE PHYSICS!

“They find out that it’s okay to be good at physics, for example, and to work on assignments long into the evening. It might not be an attitude

”Talented pupils shouldn’t be uprooted. But special provision does need to be made for them.”

Hanne Hautop

NURTURING TALENT ACROSS THE WHOLE COUNTRY

The issue has to be addressed but it has to be done within the framework of the existing education system.

“I'm not talking about elite schools. Talented pupils shouldn’t be uprooted. But special provision does need to be made for them. My vision is to expand talent-nurturing activities at elementary school level to all local municipalities, and ensure that all youth-education programmes include special elements for talented youngsters. Some

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THEME TALENTS

“At Aarhus University, around 25 pct. of a given year group of medical students choose to participate in the research year programme. A year is usually enough to give them an idea of whether this is the path to follow. You don’t need to do a whole PhD to decide. Biomedical science is about acquiring and developing new knowledge. If you haven’t managed that after six months, you’re probably not a researcher,” Jens Christian Djurhuus explains.

LINKING RESEARCH AND PRACTICE FOR YOUNG DOCTORS

Every year around 200 students in the Faculty of Health Sciences at Aarhus University choose to progress to a PhD. Approximately 100 of these are at the same time training as clinicians, and it can be difficult to do both during an ordinary day at the hospital, where the primary focus is on clinical work rather than on research.

local municipalities already make such provision, albeit usually outside regular class hours,” Hanne Hautop concludes.

Hanne Hautop has an MSc in Physics and Mathematics and taught in upper secondary schools for 13 years. She is now employed by the Ministry of Education as Talent Manager for the natural sciences.

HAVE YOU SPOKEN WITH YOUR PHD STUDENT TODAY?

Professor Jens Christian Djurhuus has been helping young people with advice on their careers in research for more than two decades. As far back as 1988, Aarhus University launched a one-year diploma course in medical health research. In 2001, Djurhuus, as chair of the Danish Medical Research Council, helped introduce the “research year”, the successor to the diploma programme, as a nationwide scheme for Master’s programmes.

It affords students the opportunity to test their research skills under the guidance of their own faculty’s researchers, an opportunity many of them find particularly attractive.

”We need a culture of closer links between research and clinical practice, a proper clinical PhD programme and a subsequent research career. Not necessarily for everyone, but for many.”

Jens Chr. Djurhuus

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“I often ask the ward management if they have remembered to treat their PhD students properly and ask about their research, because they rarely do. For the hospital, the main issue is getting the everyday work done, and that tends to detract from the PhD student’s enthusiasm for research. We need a culture of closer links between research and clinical practice, a proper clinical PhD programme and a subsequent research career. Not necessarily for everyone, but for many.”

CAREER PROGRAMME FOR TALENTED STUDENTS

Jens Christian Djurhuus is one of the brains behind the Sapere Aude Programme (Dare to Know). The name refers to the Danish Council for Independent Research’s new career programme for talented researchers, the aim of which is to develop the skills of the brightest scientists and provide career paths for them. The programme is divided into three stages – Young Elite Researcher, Research Manager and Top Researcher – and involves all five Danish research councils. The first grants were awarded in December 2010.

“The idea behind Sapere Aude is to enable researchers at different levels to see a career path based on their own ideas, as well as to attract researchers from abroad – preferably the best – to Denmark,” he adds.

Jens Christian Djurhuus is a professor, M.D. at Aarhus University and chair of the Danish Research Council for Independent Research (DFF). He conducts research into urinary tract disorders. Along with younger colleagues, he was behind a discovery that made life easier for tens of thousands of children worldwide. In the 1990s, they discovered that children who wet the bed at night lack a specific hormone. The condition can now be treated with medicine.

TALENT PRIZE KEPT ME ON TRACK

Professor Lars Juhl Jensen (36) MSc in Chemical Engineering and PhD received the Lundbeck Foundation’s Talent Prize in 2003 and its Research Prize for Young Scientists in 2010.

Lars Juhl Jensen conducts research into proteins. He and his group at the Novo Nordisk Foundation Centre for Protein Research at the University of Copenhagen study how proteins in human cells interact with each other in complex networks.

Using both his computer and his comprehensive knowledge of statistics and molecular biology, Lars Juhl Jensen processes massive amounts of biological data and his work with bioinformatics has brought him numerous awards – the Lundbeck Foundation has chosen to honour him twice.

“When I was awarded the Talent Prize in 2003, it came as a major surprise. I had just finished my PhD under Professor Søren Brunak at the Technical University of Denmark, where I also studied as an undergraduate. It’s truly encouraging to know that other people appreciate your work. It helped me stay on the right track – and then in 2010 I was also awarded the Young Scientist prize. They seem to be keeping an eye on me," he says with a smile.

”Since then I’ve been very lucky – and research definitely requires a certain amount of luck. There will always be something that goes wrong, otherwise it wouldn’t be research!”

Lars Juhl Jensen

PROGRAMMING AT AGE EIGHT

object of his curiosity was and is the human brain. He is currently conducting research into depression.

“We define depression far too broadly at the moment. My work is about characterising a particular subgroup of patients suffering from severe depression,” he explains. Approximately 30 pct. of the patients who are hospitalised with this diagnosis also have psychotic symptoms such as delusions and hallucinations. For example, some patients are convinced that they are terminally ill with cancer, even though there is no evidence of it. Others suffer from a crippling sense of guilt because they believe they are personally responsible for the financial crisis. “My goal is to explain why some people develop psychosis along with depression. In the longer term, this will hopefully lead to better targeting treatment. As things stand, treatment for depression flounders about in the dark to a certain extent. We can’t tell in advance which patients will benefit from the different types of treatment. I want to do something about that.”

TIME TO EXPERIMENT

Working with patients suffering from depression is just one part of Søren Østergaard’s PhD project. He is affiliated to the Unit for Psychiatric Research at Aalborg Psychiatric Hospital, which has been crucial for his career choice.

“During my first year, I worked in an unspecified research position, and benefited from a very specific type of talent management. I was allowed time to experiment and find the topic that interests me most. It made a huge difference to me that the objective wasn’t predefined.”

The prize from the Lundbeck Foundation has provided a further boost to his career.

“The award is an endorsement of my work, and an incentive to run at 120 km/h instead of 100. It’s also very useful when seeking funding and partners,” he explains.

The latest honour is for the work he did in 2003–09 at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Europe’s leading centre in the field. His mentor there was Dr. Peer Bork, who together with Professor Brunak have hugely influenced Lars Juhl Jensen’s research career. His father also helped him on his way, teaching Lars Juhl Jensen computer programming when he was just eight. His interest in bioinformatics was aroused after he left school, while doing a summer job at Novo Nordisk, where he worked in a bioinformatics group.

MATHS LESSONS WITH MUM AND DAD

Lars Juhl Jensen kept working for Novo Nordisk while he was studying at the university, which proved to be a great help.

“It made it easier for me to stay motivated, and it showed me the way forward. Since then I’ve been very lucky – and research definitely requires a certain amount of luck. There will always be something that goes wrong, otherwise it wouldn’t be research! I knew early on that I was interested in research but I wasn’t encouraged down that road at school. If my parents hadn’t been able to give me extra maths tuition at home, I might have lost interest.”

JUST CAN’T HELP IT

Søren Dinesen Østergaard (30) M.B. was awarded the Lundbeck Foundation Talent Prize in 2010.

Right from his first day at the medical school at Aarhus University, Søren Dinesen Østergaard knew he wanted to be a researcher. The

”And talent isn’t everything – you have to work hard and you need luck.”

Søren Dinesen Østergaard

LIFELONG PASSION

The Danish education system has never had a tradition of nurturing individual talent and has always concentrated on breadth. Not that this has held Søren Østergaard back.

“Doors open up if you’re enthusiastic enough. I think the breadth system is a good thing. It produces fully rounded individuals, both in academic and personal terms. And talent isn’t everything – you have to work hard and you need luck. For me, research has become a passion that will last a lifetime. I just can’t help it.”

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JUNIOR GROUP LEADER FELLOWSHIPS Every year, the Lundbeck Foundation awards fellowships to particularly promising young researchers and their research teams.

Each grant lasts five years and is worth DKK 10 million.

The fellowships are awarded to researchers in their thirties who are capable of building or continuing to run teams conducting research into the biomedical or natural sciences.

Recipients have typically been awarded a PhD within the last 5–7 years. The teams must be working on original frontline basic or applied research.

As well as researchers already living in the country, the Lundbeck Foundation also aims to attract researchers who are currently residing elsewhere but wish to move to Denmark and continue their research here.

The five Junior Group Leader Fellowship recipients for 2010 describe their research over the next few pages.

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BLAGOY BLAGOEV, 37 MSC IN CELLULAR & DEVELOPMENTAL BIOLOGY, UNIVERSITY OF SOFIA, PHD, UNIVERSITY OF SOUTHERN DENMARK

PLURIPOTENT STEM CELLS

RESEARCH FIELD: HUMAN STEM CELLS OBJECTIVE: TO SECURE AN IN-DEPTH UNDERSTANDING OF THE MECHANISMS THAT TURN STEM CELLS INTO SKIN, BONE, LUNG, LIVER AND ALL OTHER TYPES OF CELLS FOUND IN THE HUMAN BODY

SECURITY AND FREEDOM TO WORK

The longer-term vision is to use stem cells to treat a number of disorders caused by malfunctioning cells.

“Another objective is to strengthen links between basic and clinical research. A lot of people, many from outside the University, have contributed to the project, and I am deeply thankful for their support. It’s a joint effort, not a one-man show.”

At the University of Southern Denmark, on the outskirts of Odense, a small group of researchers is making a determined effort to wheedle out of human stem cells the secret of their ability to “specialise”. The first objective is to devise a method that will make it possible to repeat this process in the laboratory.

“A great deal is already known about stem cells, but we still do not have reliable protocols for how a stem cell develops into a specific cell, e.g. a liver cell. This is what we are trying to find out. Stem cells are being studied all over the world, but our approach, which involves mass spectrometry and proteomics, is unique. We hope to learn more about this rather complex process, and perhaps inspire new forms of treatment,” says the head of the group, Associate Professor Blagoy Blagoev.

“The grant from the Lundbeck Foundation was crucial. The DKK 10 million gives us the security and freedom to work for five years. The amount is large enough that we do not have to spend so much of our energy on sourcing additional funding. It has been a great help. I’m very grateful for that,” Blagoy Blagoev says.

STRENGTH IN DIVERSITY

Originally from Bulgaria, Blagoy Blagoev arrived in Denmark in 1999 with a Master’s degree in biology.

“The specific aspects of my Master’s thesis from Bulgaria were not obvious to the University of Southern Denmark, but it allowed me to enter their world. I had a strong grounding in theory, but no practical experience. In Bulgaria, there was no money to invest in laboratories and equipment, so moving here was like coming to heaven. I joined an international group of people, and I think it is highly beneficial for the research that people with widely different backgrounds and experience are working together. They see things differently, and that provides the group with a broader perspective.”

Blagoev’s current project involves colleagues from Denmark, Belarus, Germany and Uzbekistan.

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A chemical from a marine fungus that lives in the waters around Japan is the focal point of Christian Olsen’s project. The substance is interesting because it is capable of blocking a specific type of enzyme that has been linked with the development of cancer cells.

“It has been observed that these enzymes are upregulated in certain types of cancer. So it would be interesting if we could inhibit their activity. In the USA, certain types of lymphoma are treated with two new drugs that use this mechanism,” Christian Olsen explains.

However, even though the new drugs work in a more direct manner than traditional chemotherapy, they are still not sufficiently specific.

“There are 11 subtypes of this class of enzymes, and the two approved medicines inhibit several of the subtypes at the same time. We want to develop compounds that inhibit only one enzyme. Perhaps that

will be enough to slow the development of the cancer cell. And if we can create drugs that inhibit all 11 subtypes individually (see illustration), we will be able to affect one enzyme at a time and observe what happens. That would give us new insights into how the cell works and could, in the longer term, lead to new medicines.”

FANTASTIC OPPORTUNITY

The DKK 10 million grant from the Lundbeck Foundation will allow Olsen and his team to get started right away.

“The donation made the project feasible. It means I can hire two PhD students and a postdoc. I know how long it sometimes takes to obtain funding for projects like this, so it’s a fantastic opportunity. Research into how cells read information in genes is mainly used in the development of cancer medicines, but it is also relevant to other diseases of genetic origin, e.g. neuro-degenerative conditions such as Huntington’s disease, Friedreich’s ataxia and for cystic fibrosis. The potential is huge in this field and we hope to develop good, chemical tools that will help us understand these mechanisms, as well as to produce a lot of interesting research and turn out some good PhDs. The prerequisites are all in place now,” he concludes.

CHRISTIAN ADAM OLSEN, 36 MSC IN CHEMICAL ENGINEERING, DTU, PHD THE DANISH UNIVERSITY OF PHARMACEUTICAL SCIENCES RESEARCH FIELD: ORGANIC CHEMISTRY AND CHEMICAL BIOLOGY OBJECTIVE: TO DEVELOP ROBUST ORGANIC REACTIONS AS A PREREQUISITE FOR ENZYME INHIBITORS, WHICH ARE BELIEVED TO SLOW THE SPREAD OF CANCER AND CERTAIN NEURODEGENERATIVE DISEASES

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Library Design

Library Synthesis

Resynthesis, confirmation, SAR, and docking studies

Screening

JES KRISTIAN JØRGENSEN, 35 MSC IN ASTRONOMY, UNIVERSITY OF COPENHAGEN, PHD LEIDEN UNIVERSITY RESEARCH FIELD: STAR AND PLANET FORMATION OBJECTIVE: TO LEARN ABOUT THE ORIGINS OF SOLAR SYSTEMS

Planets and stars like our own Sun are formed when clouds of cold dust and gas collapse. The clouds obscure all visible light created in the process, so other methods of observation have to be deployed if you want to know more about the birth of young celestial entities.

Jes Jørgensen and his group at the Niels Bohr Institute are studying the infrared and sub-millimetre/radio-wave radiation emitted by these clouds of cold dust and gas.

INNATELY INQUISITIVE

“Observations on the two wavelengths can tell us about a young star’s structure and chemical composition. By studying the very early stages of the creation process, we learn, for example, about how stars accumulate mass, and when and how planets form around them,” Jes Jørgensen explains.

“The grant means we can run an ambitious research project. It will let us hire two PhD students and two postdocs, and we’ll be able to look at more areas related to the solar systems’ earliest stages. The objective is to understand more about where star systems come from,” he goes on.

WATER FOUND AROUND A STAR

His own motivation is his “innate inquisitiveness”, which he has been allowed to pursue.

Using new, advanced observatory technology like the Atacama Large Millimeter Array (ALMA) in Chile (see figure) and telescopes in Hawaii, Jes Jørgensen and his colleagues hope to answer questions about when and how galaxies are formed, how the chemistry of young solar systems evolves, and about the role of the surroundings.

“Thanks to new and improved technology, a lot is happening in space research. In 2010, along with colleagues abroad, I detected water vapour around a very young star. Nobody expected to find it and it was a seminal discovery, because water is, of course, a prerequisite for life as we know it. Now we are trying to find out more about its composition.

Is it like the water in our oceans? And how does it get to the young planets?”

Jes Jørgensen hopes the grant from the Lundbeck Foundation will help to answer many more questions.

“As a student I became fascinated by a lecture on star formation, and since then one thing has lead to another. My PhD took me to the Netherlands, where they have a strong tradition in astrochemistry.

Since then I’ve worked as a postdoc in Boston, USA, and as a staff scientist at the University of Bonn, Germany.”

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patients. The project represents what I think basic research is all about.

If funding was only available for strategic research, we would miss out on important new knowledge and insights. As a society, we can’t afford not to conduct basic research.”

Michael Pittelkow puts molecules to work. And when they are finished, he studies them to see what they can tell him. By studying how the molecules have locked themselves together, Michael Pittelkow and his team gain new insights into the building blocks from which we are all made. “Even though organic chemistry has been well described, there is still a great deal we don’t know about how molecules ‘see’ each other, and what makes one molecule bind to another. Our experiments look at how these building blocks combine to form larger molecules, and how this can be guided by molecular recognition (see figure). Our research is a kind of reverse engineering. To put it in slightly abstract terms, you might not be able actually to build bridges with it, but it will help you work out how to build the best and strongest bridge,” he explains.

BASIC RESEARCH WITH PERSPECTIVES

The team’s focus is not on molecules in bridges, however, but on human beings. A deeper understanding of the molecules’ choice of partner has tremendous potential, e.g. for treating disease.

“If we had a deeper understanding of how molecular recognition works, it would make it considerably easier to produce so-called ‘smart drugs’ that have a very specific effect or work on certain groups of

RESEARCH SHOULD BE FUN

The donation from the Lundbeck Foundation increases the scale of Pittelkow’s project.

“The grant provides the underpinnings for a major research programme – we need not only go for the low-hanging fruit. I can fill three PhD and two postdoc positions, and also buy technology that we don’t have at the moment – specifically, a device to characterize the molecules and estimate their weight. I look forward to it arriving. It will definitely be fun – and challenging,” he says.

Michael Pittelkow stresses that research should be fun.

“Otherwise, you might as well do something else. In my case, it was one of my teachers at school and my older brother who encouraged me to do chemistry because they made it fun. And it still is fun.”

MICHAEL PITTELKOW, 33 MSC IN CHEMISTRY, PHD UNIVERSITY OF COPENHAGEN RESEARCH FIELD: SYNTHETIC CHEMISTRY OBJECTIVE: TO UNDERSTAND HOW MOLECULES “RECOGNISE” AND BIND TO EACH OTHER

DYNAMIC COMBINATORIAL CHEMISTRY IN WATER

Template

Building blocks

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Dynamic combinatorial library

Templated library

THOMAS GILBERT, 33 BA IN BIOLOGY, OXFORD UNIVERSITY, DPHIL, GENETICS, OXFORD UNIVERSITY RESEARCH FIELD: EVOLUTIONARY BIOLOGY OBJECTIVE: TO STUDY THE DEVELOPMENT OF PATHOGENS AND LEARN HOW DISEASES ARE SPREAD

Old DNA and RNA can reveal how pathogenic organisms evolve over time. At the Centre for GeoGenetics in the Natural History Museum of Denmark, Thomas Gilbert and his team are studying material from infected potato plants, turtles as well as the infectious hepatitis C virus to learn how various diseases spread. By examining historical materials, the scientists hope to find answers to questions about when the diseases first appeared and how they have since spread.

LIKE ICE CREAM

“It’s really basic research, very exciting but also difficult. DNA is like ice cream – if you put it in the freezer, it’s fine for years, but on the table, it degenerates in minutes,” Thomas Gilbert explains.

The hepatitis C virus was first discovered in 1991. “That means there’s a lot of it ‘in the freezer’, and there’s much we don’t know about it.

Why does Egypt have the world’s highest incidence of infectious hepatitis (approx. 40 pct.) when it’s only about 1 pct. in Western Europe?

One theory is that the virus spread through infected needles used in mass vaccination programmes in the 1950s. By examining the virus RNA from then up to the present day, we will perhaps gain new knowledge that could pave the way for a vaccine and a treatment.”

dating from the 1800s, so we are able to monitor how it has changed over time,” he continues.

The third pathogen is found in all seven species of sea turtle and is spreading rapidly. The animals develop tumours that are located such that they prevent them from eating, so they die of starvation (see illustrations). The disease is probably due to a herpes virus, but the environment also plays a role. The team hopes to learn more about these factors.

NEW KNOWLEDGE

With the help of the grant from the Lundbeck Foundation, Thomas Gilbert and his team hope to be able to shed light on an almost unexplored field.

POTATO PLAGUE AND TURTLES

The potato plague that forced a large part of Ireland’s population to emigrate in the 19th century is still a significant – and costly – problem, e.g. in the USA. “It costs billions of dollars a year, and that alone makes it interesting to study. The potato plague has had 150 years to evolve. We have material

“It’s very difficult to obtain funding for a research field like ours, and at one point I was close to giving up on biology. Without the help of the Foundation, I would only have been able to study one of these three pathogens – at most. Now, I’ve been able to bring in staff from the USA and Costa Rica, and together we are able to explore the issues using the same theories and methods. Nobody else is doing this.”

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GRANTS OF EXCELLENCE In the Spring of 2010 the Lundbeck Foundation invited applications for two Grants of Excellence within the area of neuroscience, including clinical neuroscience and psychiatry. The grants were awarded for five years, and each grant amounts to â‚Ź 3 million.

The purpose of these grants was to improve the possibilities for ensuring internationally competitive and more powerful neuroscience research in Denmark.

It was the intention that these grants should attract excellent researchers primarily from abroad, capable of adding a significant quality boost to existing good Danish neuroscience environments.

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Fig. 1 Transcranial magnetic stimulation with two coils: Painless noninvasive stimulation targets the motor cortex of the left hemisphere in at healthy volunteer. The right panel shows the map of the induced electrical field in the cortex.

Fig. 2 With diffusion MRI, the three-dimensional displacement profiles of water molecules can be measured in white matter and axonal composition and direction can be estimated. The image shows tractography where main white matter pathways are traced by following the estimates of axonal directions. The motor tract descending from the motor cortices in both hemispheres to the brainstem and the spinal cord is highlighted in blue (dorsal view) (courtesy of Henrik Lundell).

PROFESSOR HARTWIG SIEBNER, M.D. DANISH RESEARCH CENTRE FOR MAGNETIC RESONANCE (DRCMR), COPENHAGEN UNIVERSITY HOSPITAL, HVIDOVRE GRANT OF EXCELLENCE PROJECT: MAPPING, MODULATION AND MODELLING: CONTROL OF ACTIONS (CONTACT) GRANT: DKK 25 MILLION

Professor Hartwig Siebner and his team at the Danish Research Centre for Magnetic Resonance will explore how the brain decides to perform a given action. “Recent findings suggest that the brain maintains control of patterns of action and movement by means of a dynamic interaction between different motor centres. To gain insight into and understanding of these networks, we need to visualise brain activity with the aid of multimodal imaging, brain stimulation and computer modelling,” he explains.

MAPPING AND MODELLING THE BRAIN’S MOTOR FUNCTIONS

HOW DOES THE BRAIN DECIDE TO INDUCE A MOVEMENT?

In a dynamic world, the individual is constantly forced to adjust and adapt his or her actions. Just writing an e-mail requires the brain to take many factors into consideration. What do we want to write and when? Is the e-mail private or to a colleague? External factors like the physical location of your mobile phone or computer keyboard influence how the act itself is performed. It all plays a role.

Functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) have been successfully used to identify regions of the brain that deal with motor skills.The project will focus on what is referred to as real-time fMRI, where changes in brain activity are monitored by fMRI and EEG while a person performs a motor task. Advanced modelling of measured brain activity, both at rest and during motor activities, will also be used to develop causal models for the changes in brain activity that underpin motor actions.

THE BRAIN’S MOTOR NETWORK

This example illustrates how the brain, when choosing patterns of action, constantly and flexibly responds to the demands from the brain itself and the surroundings. If we can understand the processes that lead to patterns of action in the normal brain, then perhaps we will be able to obtain insight into the brain’s function in cases of neurological and psychiatric disorders, where the ability to perform such complex actions may be impaired.

fMRI and EEG are essential methods for mapping the correlation between the brain’s activity and a movement, but these two methods are not sufficient to enable us to understand how the motor network itself functions. Transcranial magnetic stimulation (TMS) is used for this purpose. TMS is a non-invasive measurement technique that uses rapid shifts in the magnetic field around the brain to induce electric currents in the cerebral cortex. By focusing the magnetic field, specific

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motor areas are activated, so patterns of movement without conscious influence can be mapped out (see figure 1). Comparing the networks created by fMRI with and without conscious influence, provides insight into how the brain initiates and executes a movement.

Diffusion MRI is also an important research tool in the project. By measuring the movements of water molecules in the brain, this technique allows measurement of the connections between regions of the brain involved in the action. This is also known as tractography (figure 2). “Tractography based on diffusion MRI provides us with detailed knowledge of both the ‘strength’ and the nature of the anatomical connections in individual brains. This knowledge of the ‘strength’ of specific connections between areas of the brain, together with functional MRI analyses, will illustrate the interactions in the motor system during motor actions,” Siebner explains.

PREDICTING CONSEQUENCES

The brain has great experience of – and is very good at – integrating and predicting the physical, social or emotional consequences of our actions. This ability is critical for optimising decisions, e.g. what movement to make. Much of the ContAct project will focus on how the brain works in relation to its capacity to predict the consequences of a movement.

faced with countless alternatives, and therefore, simultaneously with the choice of a given action and movement, it also has to suppress a host of other options. The research project will provide an understanding of how the brain works during such a conflict: i.e. when faced with a choice between performing an accustomed movement, for which the brain has given the order many times before, and a new, unfamiliar movement required in the given situation.

WILL

A significant part of the project aims at studying the effect of will on the working brain. This research can uncover the connections and hence the patterns formed in the brain in relation to the decisions about which action to perform, when it should happen and whether it should be performed at all. ”The ContAct project can give us an understanding of where in the brain – and how – the will affects the performance of a movement. It is a fantastic opportunity to work with the exploration of the brain for younger scientific staff, and it will allow us to forge links with other researchers in Denmark and abroad. We greatly appreciate the Lundbeck Foundation’s grant, which guarantees us peace to work on such a major project,” Hartwig Siebner concludes.

THE BRAIN IN CONFLICT

Another aspect of the analysis concerns how the brain decides upon a particular action and therefore a particular movement. The brain is

PROFESSOR LARS EDVINSSON, M.D. DEPARTMENT OF CLINICAL EXPERIMENTAL RESEARCH, GLOSTRUP RESEARCH INSTITUTE, COPENHAGEN UNIVERSITY HOSPITAL, GLOSTRUP GRANT OF EXCELLENCE PROJECT: A NOVEL APPROACH TO THE TREATMENT OF STROKE. TARGETING CEREBROVASCULAR SIGNAL TRANSDUCTION IN STROKE TREATMENT GRANT: DKK 25 MILLION

Over the last many years Lars Edvinsson's group has worked on the changes that occur in the brain’s vasculature after a stroke. The latest remarkable finding has been the discovery of an upregulation of a handful of different receptors in the cerebral vessels in the area affected by the stroke. The expression of these new receptors starts at the very beginning of the stroke. The new receptors are located in the wall of the vessels that supply the tissue with oxygen and nutrients.

All of the upregulated receptors are so-called vasoconstrictor receptors, meaning that researchers have observed that upregulation of these receptors constricts the vessels, an effect that reduces blood flow to the area. This is a critical consequence, as the blood flow to the brain tissue is already severely lowered by the stroke, and this further reduction in the blood supply leads to a worsening of the brain damage.

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Stroke is a severely disabling disease and the third leading cause of death and disability worldwide after ischemic heart disease and all types of cancer combined. Ischemic stroke is caused by sudden occlusion of a cerebral artery by a clot that reduces the blood flow and thereby the supply of oxygen and nutrients to the brain tissue. Currently, clot dissolving medication is used up to 4 ½ hour after stroke onset and has been shown to have a beneficial clinical effect on the outcome after stroke. In addition, major efforts have focused on the development of neuroprotective agents that could protect brain tissue during ischemia.

However, more than 1000 different neuroprotective treatments have been identified in the preclinical setting, but so far none have proven beneficial in major clinical trials.

The upregulation of vasoconstrictor receptors in the brain vessels after a stroke is governed by intracellular signals, of which a few have so far been identified (see figure). By inhibiting these signals it has been demonstrated that researchers can prevent the upregulation of vasoconstrictor receptors and thereby improve the blood supply to the affected brain tissue after a stroke. In a number of animal studies, the group has demonstrated that this treatment saves brain tissue and normalizes neuronal function after a stroke. Thus, Lars Edvinsson believes that they have developed a new approach to limit the brain damage after stroke.

WHICH RECEPTORS ARE UPREGULATED?

Lars Edvinsson's group is the first to demonstrate the inherent capability of cerebral vessels to undergo changes in their receptor expression upon exposure to ischemia. By use of experimental models of focal and global ischemia, as well as in samples from patients following a fatal

stroke, they have demonstrated by use of confocal microscopy that novel endothelin ETB, 5-hydroxytryptamine 5-HT1B and angiotensin AT1 receptors appear (see illustration). The demonstration of strikingly similar patterns of receptor changes in rat and human cerebral arteries subjected to ischemia indicates a strong clinical relevance of this phenomenon.

A KEY QUESTION – “WHAT STARTS THE RECEPTOR CHANGES”?

behind receptor upregulation and the subsequent local vasoconstriction. With such data they will more accurately pin-point targets of therapeutic intervention. Their preliminary results have convinced them that the vasoconstrictor receptor has a crucial role in the brain damage and two of their therapeutic substances have been tolerated well by animals in initial experiments. The support from the Lundbeck Foundation Grant of Excellence will help the group on the way to their ultimate goal which is the treatment of acute stroke.

The group hypothesizes that the change in perfusion pressure caused by the stroke is one key important factor in initiating the intracellular signalling pathways leading to the receptor changes in the brain vessels.

They aim to address this pertinent question by measuring the muscle tension in the vessel wall by perfusion of isolated cerebral arteries at different flow levels and at different perfusion pressures.

CLINICAL IMPORTANCE

There is an urgent need for new ways to treat cerebral ischemia. By determining signal-transduction pathways in brain vessels affected by ischemic stroke, the group hopes to reveal the molecular mechanisms

Worsened cerebral ischemia

Stroke

Edema

Vasoconstriction

• Changes in cerebrovascular wall shear stress

Inflammation

• Other factors from ischemic brain tissue

BBB opening Vasoconstrictor GPCR upregulation ETA/B

Breakdown of BBB proteins

5-HT1B AT1

TX A2

Proinflammatory cytokines

CaMKII

MMPs

Leukocyte ERK1/2

TFs Cytokines

Cytokines

p38/JNK

Cerebrovascular smooth muscle cell

Leukocyte

THE MUSCLE CELL LAYER OF A BLOOD VESSEL WALL

PKC

The figure depicts the mechanisms behind upregulation of vasoconstrictor receptors in the smooth muscle cells in the walls of cerebral arteries after a stroke, as well as the molecular mechanisms that we have so far identified to underlie this process. The receptors are the endothelin ETB receptor, the serotonin 5-HT1B receptor, the angiotensin AT1 receptor and the thromboxane TXA2 receptors. They are upregulated by increased expression of the genes for these receptors, which involves increased levels of the mRNA for these receptors. The increased gene expression is in turn started by intracellular signals that involve specific signalling kinase such as the extracellular-regulated kinase (ERK1/2) and the protein kinase C (PKC). These signals are turned on in the cells immediately after and during the first 12 hours after stroke onset.

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THE BRAIN PRIZE

DENMARK’S FIRST MAJOR INTERNATIONAL RESEARCH PRIZE In July 2010 the Lundbeck Foundation established the independent Grete Lundbeck European Brain Research Foundation. The aim is to honour outstanding European neuroscientists and improve interaction between Danish and European research within the field by awarding the €1 million Brain Prize. The Foundation is named after Grete Lundbeck, who in 1954, with great foresight, established the Lundbeck Foundation and therefore paved the way for its research grants. The new foundation is financially secured by a grant from the Lundbeck Foundation.

The prize is presented to the three recipients by the president of the European Research Council, Professor Helga Nowotny.

The majority of the members of the Grete Lundbeck European Brain Research Foundation Board are independent of the Lundbeck Foundation, with the vice-chancellors of the universities of Copenhagen, Southern Denmark and Aarhus as ex officio members. The Selection Committee, which is composed of internationally acclaimed scientists, nominates the recipients to the Board. The Board members cannot participate in the assessment work. Director Kim Krogsgaard, M.D., heads the administration of the Foundation.

For several years, the board of the Lundbeck Foundation considered establishing a major international, personal research prize in neuroscience aimed at providing international attention to and contacts for Danish research within the field.

Exploring the international research prize “universe” revealed that the number of prizes is large and growing, and that it would be rather difficult to introduce a new prize that could have sufficient impact. A new prize needs its own profile and requires an independent awarding body to clearly signal that it is awarded exclusively based on scientific excellence. The largest personal research prizes in financial terms, of $1 million upwards, are awarded in Scandinavia, Israel and Hong Kong, with the Nobel Prizes being the frontrunner. The analysis also revealed that there are numerous compelling reasons why the Nobel Prizes have been and continue to be among the world’s most prestigious individual prizes for over a century.

The Selection Committee comprises leading and highly acknowledged neuroscientists from Europe, the USA and Asia, with Professor Colin Blakemore (Oxford, UK) as chairman and Professor Thomas Hökfelt (Karolinska Institutet, Sweden) as vice-chairman. The committee members all consider the prize an interesting innovation and a very welcome contribution to brain research. The members have been very engaged and have contributed a great part of their time and expertise during the first year. In particular, the chairman, Professor Colin Blakemore, has been very dedicated in the process of establishing the prize.

Anyone can nominate candidates for the prize, except members of the Board, the Selection Committee and the Lundbeck Foundation’s Board and administration. Recipients must have made an outstanding contribution to European neuroscience in the spectrum extending from basic to clinical research. Recipients must have worked in Europe or in

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close partnership with European researchers. The recipients must have at least a decade of research still ahead of them – however, this is not narrowly defined, since many of today’s best scientists and researchers continue to work at front-line level after formal retirement age.

Associated with the prize is an outreach programme, as part of which the recipients will interact with Danish neuroscientists via meetings, master classes and site visits, as well as through collaboration on potential projects. One particular scope of the outreach programme will be to provide young scientists with the opportunity to become acquainted with and collaborate with the recipients. Travel grants for young researchers are therefore part of the programme. The outreach programme is organized by leading neuroscientific researchers at Danish universities and the Danish Society of Neuroscience.

After an intensive PR campaign in the summer of 2010, a substantial number of nominations were received for many top-quality researchers to the full satisfaction of the Selection Committee.

The 2011 prize was awarded to three Hungarian researchers: Tamás Freund (Hungary), Györgyi Buzaki (USA) and Péter Somogyi (UK) based on their “wide-ranging, technically and conceptually brilliant research on the functional organisation of neuronal circuits in the cerebral cortex, especially in the hippocampus, a region that is crucial for certain forms of memory”.

The prize recipients with members of the foundation's board.

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The prize was presented by the President of the European Research Council (ERC), Professor Helga Nowotny, at a festive ceremony in the “Black Diamond”, Copenhagen, 2 May 2011. The three recipients held public lectures at the Biotech Research and Innovation Centre the following day.

Chief Psysician, M.D. Nils Axelsen, chairman of the board of Grete Lundbeck European Brain Research Foundation

The Brain Prize recognizes and rewards outstanding contributions to European neuroscience, from basic to clinical.

METHOD, MOTIVATION AND BALLOON DANCE In autumn 2009, five employees from the Development section at the Danish Experimentarium science centre climbed aboard a newly acquired bus for an extended tour of Denmark. After a year of intensive preparation, they were ready to take the challenging ‘Method Lab’ science course to 534 science and technology teachers in 22 municipalities.

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Method Lab is a two-day course aimed at primary school teachers who teach Science and Technology but not as their main subject. Since 1993, all science subjects in Denmark have been taught from first to sixth grade as one subject: Science and Technology.

The Method Lab course idea was born in early 2007, partly in response to the fact that not enough teachers were interested in teaching the subject.

In September of that year, following a donation of DKK 6.5 million from the Lundbeck Foundation, Experimentarium Science Centre staff commenced the process of developing the course.

OBSERVATION, MODELS, EXPERIMENTS AND THE ‘JUST-DOIT’ METHOD

Method Lab is designed to enhance teachers’ skills, present them with new ideas about how to teach scientific methods of inquiry and improve the organization of their science lessons. The course part is the focal point of the project and builds on four specific methods of study: observation, models, experiments and the just-do-it method.

The course utilises such simple materials as balloons and soap bubbles.

The teachers were clearly enthusiastic about the fact that it is possible to explore the world around us in a fun way without compromising on academic standards.

”Wonderful! The focus on methods means we will be able to instil in our pupils the courage to go out and explore the world.” new insight and inspiration. They also said that Method Lab is organised in such a way that the course content is directly applicable in their classrooms. Secondly, it emerged that although teachers are generally very positive about the course, they differ in terms of how much they subsequently apply what they have learned in their own classes.

METHOD LAB AND THE FUTURE

“When will you be running Method Lab 2?”

This question was posed to the staff several times during the tour.

Many participants felt that Method Lab seriously – and perhaps for the first time – had given them a shared foundation on which to base their classes. It is therefore gratifying that demand for Method Lab continues and the course is still part of the project timetable for 2011.

METHOD KIT – INSPIRATION FOR EVERYDAY USE

As a source of inspiration, teachers attending the course are given a 'Method Kit' toolbox. It is full of ideas for different ways to study science as well as materials ranging from pipe cleaners to alligator clips.

They are all cheap and useful everyday objects designed to inspire teachers to spend their tight materials budget of DKK 2,000 p.a. in an innovative manner. The course material also includes a workbook and the more in-depth book: Method Lab – An Anthology.

ALL OVER DENMARK

As one science co-ordinator puts it: “All other courses, incl. teacher training, only deal with the academic aspects. In other words, learning how the water cycle works. Method Lab shows us how we can actually teach it.”

The government has set a target of Danish schoolchildren being among the world’s best in science subjects by 2020. With Method Lab, Experimentarium and the Lundbeck Foundation have provided an important step on the way to reach that goal.

The Lundbeck Foundation’s donation made it possible to conduct free courses in 2009, and interest was so great that several municipalities had to be put on a waiting list.

Even if a course is free, it still costs municipalities a great deal to send teachers to Copenhagen, so the project team hit upon the idea of touring the country instead.

Local science co-ordinators, school principals and teachers were all delighted with this outreach initiative. Twenty-two municipalities throughout Denmark took part, fulfilling the team’s ambition to make Method Lab more than just a “Copenhagen project”.

POSITIVE EXTERNAL EVALUATION

The Danish Evaluation Institute conducted an in-depth evaluation of the course. The evaluation was based on three questionnaires presented to teachers who attended the course and issued immediately before, after and six months upon completion of the course.

Two main findings emerged from the evaluation process. Firstly, highly positive assessments of the course itself, which teachers say provided

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”The Method Lab course gave me the ‘missing link’ – the part of the teaching jigsaw that I lacked to put it all together.”

Alligator clips, a magnifying glass, pipe cleaners and light bulbs. The Method Kit and accompanying booklet provide insightful tips on how to teach science and technology subjects with a total yearly budget of DKK 2,000.

Books are temporarily consigned to the shelf, and the “just-do-it” method shows them just how few balloons it takes to keep two teachers in the air.

“I didn’t learn anything like this at teacher-training college – at all – ever!"

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LUNDBECKFOND INVEST A/S Is financially well consolidated, independent, and achieves stable annual returns to support the Group’s continuing business development and finance the Lundbeck Foundation’s grant activities.

Exercises active ownership of the companies in the Group focusing on long-term growth and competitive returns. The Foundation conducts its ownership through representation on the companies’ boards of directors, supported by internal analyses of business strategies, development and competitiveness.

Commercial activities are divided into: • Direct ownership: as a significant and long-term shareholder in mature, innovative and knowledge-based companies within the healthcare sector, including H. Lundbeck A/S. • Lundbeckfond Ventures: as an active investor in the establishment and development of high-tech business within life science-based venture capital companies.

• Portfolio investments: with stable annual returns. Provide the capital base for grant activities and at the same time ensure there are reserves to finance continuing development of the directly owned companies.

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ALLOCATION OF TOTAL ASSETS

H. LUNDBECK A/S 55% ALK­­­­­­­-ABELLÓ A/S 5% LUNDBECKFOND VENTURES 2% PORTFOLIO INVESTMENTS 38%

ASSET ALLOCATION OF PORTFOLIO INVESTMENTS

DANISH BONDS 14% CORPORATE BONDS 8% CASH AND CASH EQUIVALENTS 30% EQUITY HOLDINGS 38% PRIVATE EQUITY 6% REAL ESTATE 4%

THE LUNDBECK FOUNDATION'S COMMERCIAL ACTIVITIES

The Lundbeck Foundation's commercial activities are carried out through the wholly-owned investment and holding company Lundbeckfond Invest A/S (formerly LFI a/s). The activities are divided into direct holdings, venture life science investments through Lundbeckfond Ventures and portfolio investments. Lundbeckfond Invest A/S distributes dividends to the Lundbeck Foundation for the funding of the foundation's grants.

Total assets calculated at market value rose by DKK 2,372 million to DKK 26,549 million in 2010. Direct holdings, at year-end 2010 consisting of H. Lundbeck A/S and ALK-Abelló A/S, represented 60% of the assets. In 2010, ownership interests were unchanged at 70% of the capital and voting rights in H. Lundbeck A/S and 38% of the capital and 66% of the voting rights in ALK-Abelló A/S. Portfolio investments represented 38% of the assets, while Lundbeckfond Ventures represented the rest.

The strategic framework for Lundbeckfond Invest A/S is set out on the previous page. As part of the strategy, the defined goal is to expand the commercial activities in order to support the objective of the Lundbeck

Foundation of making a difference for human health. Direct holdings in mature healthcare companies and venture investments in life science companies through Lundbeckfond Ventures are part of this strategy.

2010 was a good year for Lundbeckfond Invest A/S with an increase in activities as well as profits. The companies H. Lundbeck A/S and ALK-Abelló A/S generated higher revenue and profits, and at the end of the year, the acquisition of a 36% stake in Falck A/S as a third leg of the direct holdings was announced. In 2010, Lundbeckfond Ventures completed four direct investments. The portfolio investments yielded a satsifactory return.

FINANCIAL PERFORMANCE

Lundbeckfond Invest A/S recorded a profit of DKK 2,587 million in 2010, against DKK 2,488 million in 2009.

The results from the Group companies rose to DKK 1,554 million in 2010 from DKK 1,169 million the year before. This profit was driven primarily by H. Lundbeck A/S, which recorded its best results ever.

Associated companies generated a loss of DKK 75 million, impacted principally by a loss in LifeCycle Pharma A/S. Lundbeckfond Ventures

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Bertil From, CFO of Lundbeckfond Invest A/S

recorded a loss of DKK 6 million in 2010, against a profit of DKK 30 million in 2009, attributable to investments in unlisted life science venture funds managed by Lundbeckfond Ventures. The return on the portfolio investments amounted to DKK 1,060 million in 2010, against DKK 1,304 million in 2009.

All asset classes generated a positive return in 2010, as was the case in 2009. The return on the equity portfolio was 20.3%, on Danish bonds it was 5.0% and on corporate bonds it was 14.5%. Private equity and other unlisted funds offered a return of 20.3%, whilst the return on properties was 8.8%.

Expenses amounted to DKK 19 million in 2010, up from DKK 15 million in 2009. The increase was due to higher investment activity, including the formation of Lundbeckfond Ventures.

The distribution of the portfolio investments is shown on the previous page. At the end of 2010, the greatest exposures were equities (38%), Danish bonds (14%) and cash equivalents (30%). The large cash holdings at the end of the year were due to the acquisition of 36% of Falck A/S in January 2011.

A more detailed description of developments in H. Lundbeck A/S, ALK-Abelló A/S and Lundbeckfond Ventures is provided in the separate sections on the following pages.

PORTFOLIO INVESTMENTS

2010 was a year of contrast both in terms of the economy and in the financial markets. On the one hand, the credit crisis developed into a sovereign debt crisis with problems arising initially in Greece and subsequently in Ireland, Portugal and partly Spain. Long-term interest rates in “safe” economies declined until August, and the USA embarked on new quantitative easing of monetary policy in November. On the other hand, corporate earnings were up, resulting in rallying equity prices and strong credit markets.

Portfolio investments including the property company Obel-LFI Ejendomme A/S yielded a return of just over 11.5%, equal to DKK 1,060 million, in 2010, which was satisfactory given the economic uncertainty. Portfolio investments subsequently amounted to DKK 10,214 million, against DKK 9,376 million at 31 December 2009.

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The proportion of equities and exposure to private equity and other unlisted funds was increased over the course of the year in anticipation of rising equity prices and an increase in activity in the private equity funds, in which Lundbeckfond Invest A/S has ownership interests. The duration of the bond portfolio was reduced in 2010 in step with the declining interest rates and in anticipation of yields bottoming out.

Outlook for 2011

The financial performance of Lundbeckfond Invest A/S depends on the commercial activities of H. Lundbeck A/S, ALK-Abelló A/S and Falck A/S as well as the return on the portfolio investments and Lundbeckfond Ventures. For a more detailed description of the outlook for the three direct holdings, see the corporate websites: www.lundbeck.com, www.alk-abello.com and www.falck.com.

H. LUNDBECK A/S

H. Lundbeck A/S is a global pharmaceutical company that develops medicines to treat brain disorders on the basis of its own research.

Brain disorders are often not only highly debilitating for the individual patient, but also a burden on families and costly for society. There is a clear need for better and more effective treatment for a range of such disorders.

In 2010, Lundbeck announced a research strategy based on new knowledge of disease biology and the biological connections and mechanisms that are thought to be fundamental causes of many brain disorders. This presents an opportunity to develop innovative new drugs that not only treat the symptoms but also impede the progress of diseases. Lundbeck has further enhanced external co-operation by establishing partnerships with researchers around the world.

2010 was a year of continued focus on streamlining the business, cost control as well as comprehensive activities within business development, improvement of the pipeline and product platform. The company is now clearly better equipped to cope with the expiry of patents on several key products during the period 2012–2014, as well as the price pressure exerted on the pharmaceutical industry in several countries.

Lundbeck emerged from 2010 with its highest ever turnover and a healthy increase in earnings. The company has two product candidates in the registration phase, five projects in Phase III and four projects in Phase II. This is the broadest product pipeline in the company’s history. The company also entered into a number of new partnerships in 2010, with the aim of both adding new products to the sales force and ensuring maximum utilisation of the commercial potential of existing products. For example, Merck & Co. Ltd., granted Lundbeck the rights to sell asenapin (Sycrest®/Saphris®) to treat schizophrenia and bipolar disorder outside the USA, China and Japan. Lundbeck secured agreements on Azilect® in six Asian markets, and extended its collaboration with Xian-Jannsen Pharmaceuticals Ltd. in China regarding Lexapro®.

Operating profit (EBIT) rose by just over 17 pct. to DKK 3,357 million, corresponding to an EBIT margin of 22.7 pct. compared to 20.8 pct. in 2009. The improvement in profitability was due to increased sales combined with a focus on cost control and efficiency. Spending on research and development also fell, but remains above 20 pct. of total turnover.

Net profit rose by 23 pct. to DKK 2,466 million, compared with DKK 2,007 million in 2009. This is Lundbeck’s best ever result. In line with the commercial and financial performance, the Lundbeck share increased 11.9 pct. in 2010.

Lundbeck achieved its highest ever revenue in 2010, totalling DKK 14,765 million. This represents growth of 7 pct. in comparison with 2009, and was driven by progress in the three main products (Cipralex®, Ebixa® and Azilect®), which increased revenues by a total of 9 pct., as well as increased sales of the two newest products, Xenazine® and Sabril®.

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ALK-ABELLÓ A/S

ALK-Abelló A/S is an international leader in the prevention, diagnosis and treatment of allergy, a disease that constitutes a rapidly growing health problem for many people. The treatment is based on immunotherapy. Patients are exposed to the allergen – the substance to which they are allergic – in the form of an allergy vaccine. This restores the normal tolerance in their immune system and provides a sustained reduction in the symptoms. ALK is an international leader in the development of tablet based allergy vaccines. The first product, GRAZAX®, against grass pollen allergy is approved in Europe, while tablets for other allergies are currently in the clinical development phase.

In 2010, ALK revised its strategy. The strategy plan focuses on continued growth in sales and earnings, as well as on global development and commercialisation through partnerships. As part of this strategy, and in order to focus on consolidation, ALK acquired two new companies, one in the Netherlands and one in the United States. ALK also laid the groundwork for the agreement with Japanese Torii Pharmaceutical Co. Ltd., announced early in 2011, which grants Torii an exclusive license for the Japanese market for ALK products related to the diagnosis and treatment of house dust mite allergy, including a tablet based vaccine.

For the North American market, the company has entered into an exclusive partnership with Merck for tablet based products. In 2010, ALK made preparations for the production of GRAZAX®, including related

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documentation and quality systems for North America. Merck initiated dialogue with the FDA regarding applications for the registration and market approval of GRAZAX® against grass pollen allergy.

ALK also strengthened its product range, e.g. by launching a new and improved injection vaccine, AVANZ®, on new markets, and by developing the adrenaline pen, JEXT®, which has longer shelf-life than existing products. JEXT® is expected to be marketed in the first European countries in 2011.

In 2010 ALK-Abelló A/S had revenues of over DKK 2 billion for the first time. Revenue rose 9 pct. to DKK 2,140 million and vaccine sales rose by 10 pct. Sales growth was broadly based but was also adversely affected by the implementation by Dutch and German authorities, in 2009 and 2010 respectively, of a series of austerity measures towards medicine prices and reimbursement.

Operating profit (EBIT) rose by almost 10 pct. to DKK 192 million, corresponding to an EBIT margin of 9 pct., which was unchanged compared with 2009. Total operating expenses rose by just over 10 pct. to DKK 1,948 million, compared to DKK 1,760 million in 2009. Research and development expenses totalled DKK 366 million. Net profit rose by 8 pct. to DKK 128 million, compared to DKK 118 million in 2009.

The company’s share price fell by 21 pct. in 2010.

FALCK A/S

Falck is a Nordic-based company, but at the end of 2010 the company was operating in 25 countries on five continents.

All of Falck's activities are aimed at preventing accidents and decease, providing assistance in case of emergencies, disasters or accidents, and helping people rehabilitate after illness or accidents.

Falck is the largest private ambulance operator in Europe and provides ambulance services in seven European countries in close co-operation with the authorities. Following acquisitions in 2010 and 2011, Falck also provides extensive ambulance services in the USA and Latin America.

Additionally, Falck is the largest private fire service company in Europe, with operations in ten countries.

Around 1.8 million Danes, Swedes, Norwegians, Finns and Estonians subscribe to one or more of Falck's assistance services. These services aim to provide the subscribers with the highest possible degree of safety - either through accident prevention or by helping quickly and competently in case an accident does occur. Falck's assistance services mainly focus on motor vehicles, housing, travel and health.

Falck is a global leader in providing rescue and safety training courses, particularly for employees in the offshore and maritime sectors. Falck

also provides safety training to employees from the chemical industry, the aviation industry, fire brigades and the military at more than 30 training centres in 14 countries worldwide.

In the Nordic countries, Falck Healthcare supplies health services to both private companies and the public sector. This service is primarily provided at one of Falck’s more than 200 health centres across the region.

In 2010, Falck took further significant steps towards becoming a global organisation, and Falck’s ambulances now also provide rescue and safety services to citizens in both North and Latin America. Additionally, Falck has never before provided so many people with rescue and safety training at a growing number of training centres around the world.

Falck has also strengthened its assistance services in the Nordic countries considerably through agreements with new, strong partners.

In 2010, the Falck Group achieved a revenue increase of 11.1 percent, to DKK 8.4 billion. Revenues from operations outside Denmark increased in line with previous years, and amounted to 36.7 percent – up from 34.6 percent the year before. Thus, growth in markets outside Denmark was 18.2 percent of which organic growth accounted for 6.7 percent. Organic growth in Denmark was 4.2 percent. This growth is reflected in the results for the year, with a 16.3 percent EBITA increase to DKK 839 million.

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LUNDBECKFOND VENTURES Lundbeckfond Ventures is an evergreen life science venture fund established by Lundbeckfond Invest in the autumn of 2009. The structure as an open evergreen fund allows flexibility in the investment approach and allows Lundbeckfond Ventures, when appropriate, to take a long-term perspective in its investments. At present, Lundbeckfond Ventures expects to invest in 3-5 companies per year.

Lundbeckfond Ventures invests in the pharmaceutical, biotech, medtech and diagnostics areas. The primary focus is on private companies with early clinical projects and medtech businesses that have been developed to the stage of either having regulatory approval or are in the processes of obtaining such. In terms of pharmaceutical and biotech programs, speciality pharma indications are of particular interest.

The primary geographical focus is Europe, but Lundbeckfond Ventures will selectively invest in the US through its network. Lundbeckfond Ventures takes the role of lead and co-lead investor in northern Europe and invests with investors with similar views on the plans and goals for the companies.

INVESTMENTS IN 2010 During 2010 Lundbeckfond Ventures invested in four companies: EpiTherapeutics, Asante Solutions, Syntaxin and DBV Technologies. Lundbeckfond Ventures is also responsible for Lundbeckfond Invest’s investment in LifeCycle Pharma A/S and the investments in unlisted life science venture funds that previously have been managed by Lundbeckfond Invest. During 2010, the Lundbeckfond Ventures team reviewed a large number of investment opportunities and established a network of advisors and consultants.

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Johan Kördel, Senior Investment Director Mette Kirstine Agger, Executive Director, Head of Lundbeckfond Ventures Casper Breum, Investment Director

INVESTMENT TEAM During 2010 a third member was added to the Lundbeckfond Ventures team. An important quality of the team is the broad operational, business development and management experience from the industry and that it taps into an extensive international network within both the biotech and pharmaceutical world. Lundbeckfond Ventures involves itself actively in developing the portfolio companies and work in close collaboration with their management and their board of directors.

PORTFOLIO NEWS 2010

LifeCycle Pharma A/S Lifecycle Pharma (LCP) appointed a new CEO late 2009 and during 2010 added several senior management team members and at the same time refocused the company and reduced head count. In July, positive results from Phase 2 clinical trials were concluded with the lead compound LCP-Tacro™ in both de novo kidney and de novo liver transplant patients. In August, LCP received a Special Protocol Assessment (SPA) from the FDA for LCP-Tacro™ regarding a pivotal Phase 3 study in de novo kidney transplant patients and phase 3 studies were started. The company also improved its financial position by completing a share offering in November, which was fully subscribed,

bringing in DKK 442 million in net proceeds. This funding is expected to enable LCP to fund the full development of LCP-Tacro™ until NDA/MAA submission in the US and EU, respectively.

EpiTherapeutics The start-up company EpiTherapeutics has made significant advances both organizationally and scientifically this last year. It has further attracted both Astellas Ventures and Merck-Serono Ventures as additional seed investors and landed a well funded three year research collaboration with Abbott on new targets.

PORTFOLIO 2010

Easy-to-use, disposable insulin pumps that are affordable, reliable, and have strong appeal to patients in terms of user friendliness and physical appearance.

Programs in clinical development for immunotherapy treatment of food allergies with the lead program in Phase Ib targeting peanut allergy. The allergens are administered epicutanously through a medical plaster, Viaskin®.

dbv

technologies

Developing novel innovative cancer drugs based on the world leading research in epigenetics conducted by Professor Kristian Helin and his group at the University of Copenhagen.

Progressing LCP-Tacro™ for immunosuppression through phase III. Its first product was FDA approved in 2008 and other programs are in earlier clinical development based on a novel drug delivery platform, MeltDose®. (LCP, NASDAQ OMX)

Targeted Secretion Inhibitors

Developing a new class of bio-pharmaceuticals to treat disease through targeted inhibition of cell secretion. The leading program is in pain and progressing in phase II (licensed to Allergan), other earlier internal programs in acromegaly and cancer.

43 Targeted Secretion Inhibitors

SUMMARY OF FINANCIAL STATEMENT FOR THE FOUNDATION 2010

DKK millon

Share of results of H. Lundbeck A/S, ALK-Abelló A/S and associated companies 1,554 Investment income from Lundbeckfond Invest A/S 1,052 Operating costs in Lundbeckfond Invest A/S (19) INCOME STATEMENT FOR THE YEAR ENDED 31 DECEMBER 2010

COMMERCIAL PROFIT

2,587

Investment income in the Lundbeck Foundation Operating in the Lundbeck Foundation

130 (17)

NON-COMMERCIAL PROFIT

113

Income before tax Tax

2,700 3

Result for the year before grants

2,703

NET ASSETS AT 31 DECEMBER 2010

Commercial investments:

Shares in H. Lundbeck A/S, ALK-Abelló A/S and associated companies 8,498

Portfolio investments, etc.

10,361 18,859 Non-commercial investments: Financial assets in the Lundbeck Foundation Property and buildings Receivables and cash

Total assets Amounts granted and payables, etc.

2,651 27 333

3,011

21,870 917 20,953

The Lundbeck Foundation is subject to the Danish Commercial Foundations Act and the Danish Financial Statements Act, and the Foundation’s financial statements will be submitted to the authorities together with the consolidated financial statements of the Lundbeckfond Invest Group, comprising the wholly-owned subsidiary Lundbeckfond Invest A/S, as well as the H. Lundbeck Group and ALK-Abelló Group.

The above financial statements differ from the provisions of the mentioned Act as regards specifications and presentation.

The commercial shareholdings in H. Lundbeck A/S and ALK-Abelló A/S are measured at equity value, a total of DKK 8,252 mio. The total market value of Lundbeckfond Invest A/S’ shareholding in H. Lundbeck A/S and of B shares in ALK-Abelló A/S, measured at market prices at 31 December 2010, was DKK 15,617 mio.

44

BOARD OF TRUSTEES

(FROM LEFT) JES ØSTERGAARD, DIRECTOR, CIVIL ENGINEER THORLEIF KRARUP, VICE-CHAIRMAN LUNDBECKFOND INVEST A/S, DIRECTOR, B.SC. (ECON), B.COM.

KIM KLITGAARD, OPERATOR, ELECTED

BY EMPLOYEES KEN LILJEGREN, SENIOR PROJECT MANAGER, CIVIL ENGINEER, ELECTED

BY EMPLOYEES

MIKAEL RØRTH, VICE-CHAIRMAN, PROFESSOR, CHIEF PHYSICIAN, M.D. NILS AXELSEN, CHIEF PHYSICIAN, M.D. MOGENS BUNDGAARD-NIELSEN, CHAIRMAN, DIRECTOR, CIVIL ENGINEER, B.COM.

PETER ADLER WÜRTZEN, RESEARCH SCIENTIST, PH.D., ELECTED BY EMPLOYEES JØRGEN HUNO RASMUSSEN, CHIEF EXECUTIVE OFFICER, CIVIL ENGINEER

EXECUTIVE MANAGEMENT

STEEN HEMMINGSEN

ANNE-MARIE ENGEL

MANAGEMENT STEEN HEMMINGSEN, MANAGING DIRECTOR, PH.D GRANTS ADMINISTRATION /SECRETARIAT BRITT WILDER, EXECUTIVE SECRETARY

BERTIL FROM

RESEARCH ANNE-MARIE ENGEL, DIRECTOR OF RESEARCH, PH.D SISSEL VORSTRUP, ASSOCIATE DIRECTOR OF RESEARCH, M.D. ULLA JAKOBSEN, SCIENCE MANAGER KIRSTEN LJUNGDAHL, SECRETARY

FINANCE AND INVESTMENT BERTIL FROM, CHIEF FINANCIAL OFFICER CLAUS KØHLER CARLSSON, DIRECTOR, ACCOUNTING & TAX VIBEKE P. BACHE, HEAD OF ACCOUNTS SUSANNE BERNTH, SENIOR CONTROLLER NINA KAMILLE HOLMGAARD, ACCOUNTING ASSISTANT

METTE KIRSTINE AGGER LUNDBECKFOND VENTURES METTE KIRSTINE AGGER, EXECUTIVE DIRECTOR, HEAD OF LUNDBECKFOND VENTURES, MBA JOHAN KÖRDEL, SENIOR INVESTMENT DIRECTOR, PH.D, ASSOC. PROFESSOR CASPER BREUM, INVESTMENT DIRECTOR, MBA

THE LUNDBECK FOUNDATION ORGANISATION

THE LUNDBECK FOUNDATION A commercial foundation established in 1954 to maintain and expand the Lundbeck Group and to provide funding for scientific research.

RESEARCH GRANTS EUR 55 M / YEAR

100%

LUNDBECKFOND INVEST A/S Investment & holding company

PORTFOLIO INVESTMENTS

70%

38%

36%

H. LUNDBECK A/S

ALK-ABELLÓ A/S (66% of the votes)

FALCK A/S

LUNDBECKFOND VENTURES

50%

OBEL-LFI EJENDOMME A/S REAL ESTATE

PORTFOLIO COMPANIES

Lundbeckfonden Vestagervej 17 DK-2900 Hellerup

ISSN 1901-5933 Design: Klaus Wilhardt Photo: Pernille Ringsing Maud Frisenfeldt Jakob Boserup

Tel +45 39 12 80 00 Fax +45 39 12 80 08 www.lundbeckfonden.dk

Motivates, in by awarding res Supports independent re with special focus on Promotes intern supporting collabora and

www.lundbeckfonden.dk www.lundbeckfondinvest.dk www.lundbeckfondventures.dk