White Paper II A Stronger Biomedical Research For A Better European Future

Executive summarylll5The white paper makes five keyrecommendations which should underliefuture policy and strategy for biomedicalresearch in Europe:1. Citizens and patients should be closelyengaged with biomedical research2. The results of biomedical research shouldbe rapidly and efficiently brought to thepatient3. Biomedical research should be conductedwith high quality in an open, honest andtransparent way4. European biomedical research should beconducted within a global context5. Investment should be increased to createthe right world-class biomedical researchbiomedical research in Europe compared with itsinternational collaborators is assessed.Europe spends substantially less per person onbiomedical research than does the US. Despite this,the share of worldwide biomedical research publications produced by EU countries has remainedstable over recent years while that of the US hasfallen: in 2009 Europe had a higher share of worldpublications, at 38%, than the US at 33%. While USbiomedical research tends to be published in journals with greater influence than research from theEU, as measured by citation rates, the gap is closing.In spite of the significant difference in funding, Europe is punching above its weight in termsof biomedical research when compared with theUS. Emerging economies such as China, India andA Stronger Biomedical Research for a Better European FutureMedicine is advancing at a rapid pace. Genomesequencing is becoming routine, and the prospectof medical treatment tailored to individual patientson the basis of a genetic profile is now realistic. Stemcell technology is progressing at a fast rate, withnew possibilities for replacing damaged cells andtissues. Innovations in information technology areproducing powerful new imaging and diagnostictechniques.These technological advances are not happening in a social, cultural or economic vacuum. Inthe West we are on average living much longer andhealthier lives than just a few generations previously. However, society is changing both withinEurope and globally. In Europe we are facing anumber of great challenges: an ageing population,obesity and metabolic syndrome, mental health disorders, allergy and chronic diseases – and cancerand cardiac diseases as the big ‘killers’. Healthcareexpenditure is rising as we can do more and populations expect more. Globally, the geopoliticallandscape is being reshaped, with powerful neweconomies emerging, such as China, India andBrazil.It is against this backdrop that the EuropeanMedical Research Councils (EMRC) have produced this new White Paper, “A Stronger BiomedicalResearch for a Better European Future”. It complements and updates the previous White Paper,published four years ago, “Present Status and FutureStrategy for Medical Research in Europe”.This white paper presents a thorough examination of the present status of biomedical researchin Europe and the rest of the world with a specialattention to the North-American situation. Througha detailed analysis of funding and of data relatingto research publications, the relative strength of

Brazil are catching up. Globalisation presents issuesof greater competition, but it also gives rise to newopportunities for international collaboration, whichshould be fully exploited. The white paper providesa detailed description of how biomedical researchactivity is distributed across regions within Europe,and also provides, for purposes of comparison, adescription of how research is organised in the USand Canada.In the future global collaboration and cohesion will be needed more than ever to overcomethe grand challenges of tomorrow. Investment inmedical research has been shown to yield a returnof 39% per year perpetually, so appropriate fundingand best practice for medical research are not onlyessential to secure health and welfare in Europe andthe rest of the world, but also make sound economicsense.A Stronger Biomedical Research for a Better European Future6

1.IntroductionlllBiomedical Research –the science of the 21st centuryThe ultimate aim of biomedical research is toanswer medical questions leading to the discoveryof treatment, prevention and diagnosis of diseasesthat cause illness and death. It is a vast field of science that includes parts of life, physical and socialsciences. It is commonly divided into basic research,which broadly investigates the underlying processesof living organisms to help understand how theyfunction; and clinical research, which applies basicresearch discoveries to human subjects to determinethe effectiveness and safety of drugs, methods anddevices used to diagnose, support and maintainindividuals during and after treatment for diseases. Translational research has recently emergedas a new discipline to emphasise the importanceof translating basic research ‘from the laboratorybench to the bedside’.Molecular medicineA consequence of the human genome project, completed more than a decade ago, was the developmentof advanced genome sequencing technologies thatcan now produce an individual’s genome sequencein an afternoon. Many thousands of genetic variations have now been found that are associatedwith an increased risk of diseases such as heart disease, stroke, diabetes, dementia and cancer. Highthroughput sequencing is just one of the new technologies that pose enormous challenges to modernbiomedical research and to clinical practice.Large data sets need large data repositories andthe capacity to manipulate and analyse the information. Storage of biological data was until recentlybeing measured in terabytes (a million millionbytes) but is now already in the tens of petabytes (apetabyte is a thousand terabytes) and will increasea further million-fold by 2020. Making good useof this technology for patient care means couplingthe capacity of genomics to large epidemiological cohorts and biological specimen collections innational and international biobanks1.Understanding the biological consequences ofgenetic variation requires an integration of other‘-omics’ approaches at the protein, RNA andmetabolite level. Putting this together, with a lot ofmathematical modelling, structural biology and epigenomic analysis will lead to an integrated systemsapproach to medicine and towards an increasingindividualisation of treatment and healthcare, awayfrom the more generalised treatment and preventionthat we are used to. Such personalised medicine willplace much greater burdens on our health systems to1. ESF Position Paper ‘European Biobanks and sample repositories –relevance to Personalised Medicine’, 2011, ISBN: 978-2-918428-41-1.7A Stronger Biomedical Research for a Better European FutureThis new EMRC White Paper, “A Stronger BiomedicalResearch for a Better European Future” follows thewell-received first white paper published four yearsago, “Present Status and Future Strategy for MedicalResearch in Europe”. The new white paper presentsan updated and more detailed analysis of the current state of biomedical research in Europe andidentifies a number of recommendations on howbiomedical research can be further strengthenedto provide a better future for Europe, its citizensand industry as well as better global healthcare andimproved human welfare generally.

A Stronger Biomedical Research for a Better European Future8Figure 1.Biomedical research interactswith three key contextualareas.diagnose and treat individuals using the best available technology.Other technologiesThis molecular approach to medicine is taking placealongside advances in other areas such as medicalimaging2, regenerative medicine3 (e.g. throughthe use of stem cells), nanomedicine, electronicimplants and proton therapy. While new technologies open possibilities for improving medical care,they can also present new risks and require moremonitoring and follow-up. MRI and ultrasoundimaging for example may reveal pathologies thatare incidental to the condition being evaluated.Small modifications to diagnostic technologies ortreatment modalities can therefore have significantknock-on effects for health services and for thepatient’s perception of health and wellbeing.Social factorsResearch on the factors inf luencing health isrevealing the importance of health inequalitiesin determining the outcomes and distribution ofhealth burden. Social, economic and environmental determinants of health have a significant impact2. ESF Science Policy Briefi ng ‘Medical imaging for improvedpatient care’, 2007.3. ESF Science Policy Briefi ng ‘Human stem cell research andregenerative medicine – A European perspective on scientific,ethical and legal issues’, 2010; ISBN: 978-2-918428-12-1.and key behavioural risk factors may be as important as genetic or other biological factors. Lifestylesthat include poor diet, exposure to tobacco smoke oralcohol and lack of physical exercise carry high levelsof risk and may be coupled to educational status orincome. Understanding the social and environmental determinants of health is complex and requiresdifferent research strategies and methodologies.Ameliorating the environmental determinants ofhealth will require the engagement of many sectorsof society outside the health services. In Europearound 18% of deaths (1.7 million per annum) aredirectly attributable to environmental factors andaccount for a third of the total burden of diseasefor children and adolescents under 19. Health systems may need to develop differential capabilities tohandle the geographic variation in environmentalimpact. This suggests a need for increased researchin health systems, social sciences and health economics alongside biomedical and clinical research.Because of its impact on society, biomedicalresearch in particular is poised to become the predominant science of the 21st century. However, thiswill happen only if it interacts successfully withthree key areas shown in Figure 1: society, in whichit is anchored and for whom it can help solve ‘grandchallenges’; Europe, as its nurturing ground of scientific excellence; and the world, which will offerboth competition and collaboration.

Improvements in sanitation, living standards andhealthcare in Europe have seen our population living longer and enjoying overall healthier lives. Manyof the fatal diseases of a century ago are no longerlife-threatening thanks to discoveries and advancesin medicine. But the changing demographics haveresulted in a shift towards an increasing prevalenceof chronic diseases and acute diseases becomingchronic, ranging from cardiovascular disease, diabetes and cancer through cataracts and incontinence.As stated in a report published in 2010 by the ESFStanding Committee for the Social Sciences (SCSS)and EMRC, the ageing of populations is one of themain economic and social developments shapingthe 21st century4. In Europe the number of peopleover 50 is expected to more than triple by 2050.In the population overall death rates per 100,000from cardiovascular disease and cancer are fallingbut together these diseases account for around 75%of all deaths in the over 65s, and those in the lowersocio-economic groups have a 30-65% higher riskof developing a chronic disease than those in thehigher. Ageing brings with it different physiologicalproblems: frailty, late-life depression and dementia.Often these diseases can occur together presenting amore complex clinical picture. Beside the strain onsociety resulting from a combined reduced workingage workforce and a higher retired population, anageing population will also lead to an expansion ofage-related disorders such as degenerative diseases.If the aim of leading an independent life in generalgood health in old age is becoming more realistic,new medicines, treatments and diagnostic tools willbe needed5.Europe is also facing a serious public health issueassociated with poor dietary habits and lack of physical activity. Obesity is a major problem: about halfof the EU population is now considered overweightor obese6. Another epidemiological challenge is theemergence or re-emergence of infectious diseases in4. ESF Forward Look report ‘Ageing, Health and Pensions inEurope: An Economic Perspective’, 2010, ISBN 978-2-918428-169; ESF Science Policy Briefing ‘Ageing, Health and Pensions inEurope: An Economic Perspective’, 2010, ISBN 978-2-918428-22-0.5. Huber and colleagues recently proposed a new definition ofhealth as ‘the ability to adapt and self manage’ in the face of social,physical, and emotional challenges because the World HealthOrganization (WHO) definition as complete wellbeing is no longerfit for purpose given the rise of chronic disease. Huber M et al. Howshould we define health? BMJ, 2011, 343: 235-237.6. Eurostat yearbook 2010 (Product code: KS-CD-10-220; ISBN:978-92-79-14884-2 ; ISSN: 1681-4789; DOI: 10.2785/40830),available online at l/product details/publication?p product code KSCD-10-220.Europe and the world. Diseases like malaria, HIV/AIDS and tuberculosis affect around 300 millionpeople worldwide. As the H1N1 influenza pandemic demonstrated, and as was discussed at anESF Colloquium in April 2010 on the managementof medical risk in European society, health willbecome increasingly influenced by the process ofglobalisation. The rate and scale of global changeon demographics, mobility dynamics, agricultureand trade among many other complex factors areyet to be fully understood to respond to emerging infectious diseases like H1N1 or Severe AcuteRespiratory Syndrome (SARS). Climate change willalso need to be taken into account as we are alreadyseeing shifts in the geographical distribution of diseases such as Lyme disease or malaria. Furthermore,climate and globalisation will raise new challengesin the health needs of migrants. Finally, the role ofthe environment on diseases and more generally therole of lifestyle and environmental factors is increasingly recognised for their major impact on health7.The increasing incidence of chronic inflammatory disease observed in industrialised countries isclearly linked to environmental and lifestyle factors.Nevertheless, there is evidence of familial inheritance in a number of diseases. Consequently, diseasessuch as asthma, allergy, and inflammatory boweldisease (IBD) are widely considered to be due to acombination of environmental and individual riskfactors8.Europe – the biomedical researchenvironment in the 21st centuryTo address these challenges, biomedical researchin the 21st century needs to be well prepared andwell organised. Breakthroughs in life and health sci7. This was recently addressed for male reproductive healthdisorders in an EMRC Science Policy Briefing, the first suchpolicy document in Europe (ESF Science Policy Briefing ‘MaleReproductive Health – Its impacts in relation to general wellbeingand low European fertility rates’, 2010, ISBN: 978-2-918428-23-7).It raised awareness on an area that received little attention so farbut where impaired male fertility is resulting in lower birth ratesespecially in industrialised countries. This is actually only one ofmany emerging research areas in biomedicine studying the impactof lifestyle and more generally the environment.8. This will require significant and integrated investment inresearch, without which the effectiveness of European healthcarewill be weakened. To maximise the potential of future healthcarestrategies, insights will be required from a number of differentfields, including epidemiology, genetics, cell biology, immunology,and bioinformatics, all feeding ultimately into effective clinicalresearch. This is currently being investigated in an EMRC ForwardLook for which more information can be found in a review bythe Forward Look Scientific Committee: Renz et al., Geneenvironment interactions in chronic inflammatory disease, NatImmunol, 2011, 12:273-7.9A Stronger Biomedical Research for a Better European FutureSociety – the big challengesfor the 21st century

A Stronger Biomedical Research for a Better European Future10ences cannot be planned but for the most creativeresearchers to express themselves and for innovative fields to emerge, it is vital to create the mostfavourable scientific environment and researchinfrastructure. The construction of a real EuropeanResearch Area (ERA), based on research excellence,is a key factor for European competitiveness.European cooperation schemes, student andresearcher mobility and bilateral partnershipsneed to form the backbone of research in the ERA.Research teams must be motivated and supported toparticipate in such initiatives. However, this alonewill not be sufficient to allow the ERA to reach itsfull potential: the sum of coordinated or integratedresearch programmes for example only accounts forabout 15% of the total budget for public research inEurope. ERA will only reach its full potential whenthere is also a ‘mobility of themes’ where researchinventories, priorities, and decisions are no longerbased on national considerations but take intoaccount complementary European skills and highcritical mass. Investment in major facilities such asCERN for Europe or ITER9 in an international context, show that this approach is possible, even if ittakes decades of continuous and convergent actions.Biomedical research in Europe will need to beresourced at an appropriate level. As will be madeevident by this white paper’s chapters on scientificpublications and funding in biomedical research,despite recent progress more needs to be done.EMRC recommended in 2007 a doubling of public funding for biomedical research but today weremain well behind the US, our biggest competitor,where about 50% of public funding goes to biomedical research, with the comparable figure for Europebeing only 30%. While the number of publications isgreater in Europe than in the US, European publications have less impact.A further challenge for biomedical researchin Europe is its diversity. As reflected later in thisreport, the majority of funding and productivity isconcentrated in only a few countries. These majorperformers of health research and development(R&D) receive more than 84% of the public spendon biomedical research, producing as a consequencesome 80% of all European scientific papers.That said, progress is being made in Europe.For example the weight of funding towards healthdirectly – besides a large share for the non-researcharea and specific cross-sectional funding – hasincreased in the successive Framework Programmes(FP) for Research and Technological Development9. CERN, European Organization for Nuclear Research; ITER,International Thermonuclear Experimental Reactor.from about 10% in the early 1990s to 15% in thecurrent programme10. There is also encouragingprogress for research infrastructure in Europewhere the European Strategy Forum on ResearchInfrastructures (ESFRI) is leading advances towardsunity and international impact in the field of biomedical research infrastructures. ESFRI now hasthi

duced this new White Paper, " A Stronger Biomedical Research for a Better European Future". It comple-ments and updates the previous White Paper, published four years ago, " Present Status and Future Strategy for Medical Research in Europe". This white paper presents a thorough examina-tion of the present status of biomedical research