EMBL's fourth decade

Summary

An interview with Iain Mattaj, Director General of the European Molecular Biology Laboratory (Heidelberg, Germany)

EMBO reports (ER): You were elected Director General of the European Molecular Biology Laboratory [EMBL] in May this year. What do you see as the main challenges for EMBL in the future?

Iain Mattaj (IM): There are two different types of challenge. One is to maintain EMBL's position as one of Europe's leading research institutes. A second is more banal but certainly no less difficult. This is to maintain political, and therefore financial, support for EMBL in its member states. EMBL must continue to serve its member states in ways that are complementary to their own national scientific systems. I also think that EMBL has a role to play, along with other international organizations, in bringing the new European Union (EU) member states on board scientifically.

There is no need to build up individual groups so they each have all the expertise

ER: On the scientific side, you plan to put more emphasis on systems biology. Why?

IM: Two reasons. Molecular biologists have used the reductionist approach to study many components within cells and organisms, so we have a lot of information about individual functions and we know which molecules are involved in producing some individual phenotypes. What is important now is to provide more quantitative and dynamic information on how molecules work together in ways that are not predictable from their individual properties, in order to understand how modules of function work as systems. We need to model different aspects of biology to generate new and more complete hypotheses about how things work. Testing these hypotheses will again require the deployment of reductionist tools. Only by deeply understanding biological functions will we be able to manipulate them and fix them when they go wrong.

The second aspect is the coming of age of functional genomics technologies, which produce very large quantities of undigested data. We need computational approaches to extract information from this data. Both of those aspects lead to my belief that we need to incorporate computational methods more extensively within the framework of EMBL, and in the framework of molecular biology in general. We have a good start at EMBL because we have been strong in bioinformatics—we have the European Bioinformatics Institute [EBI] in the UK and the Structural and Computational Biology Unit here in Heidelberg. I think we can build on this, and are already building on this, particularly in the Cell Biology and Biophysics Units. Using computational methods in different ways helps us to understand the complexity of biology in a much more profound way.

ER: Do you see this development as a step away from reductionism towards a more holistic approach?

IM: Certainly, there is a step towards a more holistic approach. However, one needs to be very careful here because the power of reductionist techniques has not yet been exhausted. I firmly believe that, for the foreseeable future, we will continue to apply these methods. But they need to be combined with approaches that look beyond individual molecules, which means using modelling methods to see which of the many combinations of different interactions between gene products is worth testing by reductionist methods. Assume that human beings have 23,000 gene products—in fact, they have roughly 23,000 genes, so there is many more than that number of gene products because of alternative splicing, protein modifications, and so on. The gene products work in combinations, and the factorial of 23,000 is an absolutely vast number. We need to cut down the number of combinations of gene products that we want to look at in detail, by all intelligent approaches available if we are to come to terms with the complexity of biology.

...the organization and funding of infrastructures for life sciences in Europe needs to be better organized...

ER: Will this also change the nature of research towards larger research groups, more cooperation and more reliance on large infrastructures?

IM: Yes, in terms of cooperation between research groups and between disciplines. Certainly, research in the life sciences is becoming more interdisciplinary. Again, EMBL has some advantages in this situation because our structure favours collaboration between groups. We have relatively small groups who can tackle important problems using a multitude of methods by combining their efforts. We are also in the process of setting up what we call EMBL Centres, which are groupings of researchers in which everyone who has common interests that extend across the boundaries of the individual EMBL Units can participate. Examples of these are the Centre for Computational Biology, the Centre for Molecular and Cellular Imaging, the Centre for Disease Mechanisms, and the Centre for High Throughput Functional Genomics. These provide opportunities to develop technologies that need to be applied across EMBL in different research activities, and allow people to come together to exchange expertise. There is no need to build up individual groups so they each have all the expertise. Instead, we want to encourage people to pool their knowledge and their intellectual resources, as well as their experimental and technical resources.

ER: Another aspect of this approach is the need for research infrastructure. Do you think Europe has any general problems with research infrastructure?

IM: I certainly think that the organization and funding of infrastructures for life sciences in Europe needs to be better organized. This is recognized by many people at both the national and the European levels. Let's use the EBI as an example: many people see that the data resourses provided by the EBI are essential for life scientists in many walks of life. People who work in industry, agriculture, academic research and in start-up companies all use bioinformatics. Ecologists use bioinformatics, clinicians use bioinformatics—all of them need access to the information that the EBI holds. But the way in which the EBI is funded does not do justice to the European scale of its mission or to its importance as an infrastructure that supports such a broad span of life science research. The EBI is not unique in this regard—there are other types of infrastructure that are, or could be useful for the research community. It's not that people don't recognize this, but that we don't yet have a well-organized mechanism by which these infrastructures can be selected and funded. I think the funding bodies may be afraid of the apparent permanence of infrastructures. They don't want to commit a lot of money over a long time period. However, infrastructures should be made subject to peer review like any other part of the life sciences, and when their useful life is over they can be stopped. The EBI is reviewed in detail every four years. Funding also needs to be competitive. If someone has a better idea of how to set up an organization like the EBI, then the EBI should have to compete with that organization for funding. I don't see any problem with this as a mode of operation. What I do see as a problem is a lack of stable funding for maintaining infrastructures. In the life sciences because of the nature of infrastructures, maintenance costs are often higher than start-up costs, but it is much easier to obtain funding for something new than for existing valuable resources.

ER: EMBL, CERN and the European Southern Observatory [ESO] are examples of research infrastructures that are funded by interested governments rather than the EU. Do you see this international, intergovernmental funding base as an advantage compared with national or EU funds?

IM: There are certain things that need to be organized on a European scale—some things can even be considered worldwide in scale—because they are too expensive for individual countries to fund; ESO and CERN and EMBL are examples of this. It makes good sense for the EU to be involved with such organizations, because they are quintessentially European, and exactly the type of organizational structure from which all of the member states benefit.

...EMBL is not competitive on a financial basis with leading research institutions in the USA

ER: But if the EU or any other intergovernmental structure funds your institution, then you are dependent on the whims of politicians.

IM: That may be true, but with 18 member states, EMBL is not immune to the political wishes of the individual states. Our member states are not identical to the member states of the EU, but they overlap significantly. The EMBL member states have set up a very good system for reviewing the activity of the Laboratory through the Scientific Advisory Committee. It reports back to the EMBL Council on what EMBL is doing and gives advice on whether planned activities are worthwhile. I see no reason why the EU cannot devise methods to evaluate research activities just as well as the EMBL member states have done. In the Research Directorate of the European Commission [EC]—first under Commissioner Philippe Busquin and now under Commissioner Janez Potocnik—I see a real desire to respond to the scientific community's wishes to have a top-quality evaluation system. This is not straightforward to set up, but the political will is there. If that will is put into practice, I would not see a danger in institutions being funded by the EU.

ER: Do you think institutions funded by interested nations could be an alternative to the EC's Framework Programmes?

IM: I think they do very different things. I think both forms of funding add value to national funding by fulfilling roles that are not adopted by national research institutions or funding agencies.

ER: But CERN and EMBL enjoy a better reputation among scientists than do the Framework Programmes.

IM: There are two major reasons for this: one is the way in which scientific review is handled, and the second is the way in which the finances and the control of funding are handled. In any opinion, the methods for the evaluation of projects within the EC's Research Directorate have been greatly improved in the past few years. What is difficult is the bureaucracy, the complexity in handling applications and the way in which money is given to research projects. Here I think things need to be simplified.

ER: By various measures, EMBL is ranked as the leading European research institute in biology, and has been ranked 13th worldwide on the basis of scientific publications. How will EMBL catch up to the 12 higher-ranked US institutes?

IM: I see the detailed evaluation of EMBL by the external expert panels selected by the Scientific Advisory Committee as a better source of feedback on the performance of EMBL's units. They give us positive feedback when we are doing well, and criticism when we are doing badly. Often the EMBL Units are evaluated by these external experts as being world-class. I think we can nevertheless continue to improve, but I don't think there is an objective measure that tells you when you are the 13th best in the world and when you are the third best. One has to continue to improve, independently of where one sits in the rankings.

ER: Still, how can EMBL compete with US universities when it comes to attracting researchers and senior staff?

IM: Clearly, EMBL is not competitive on a financial basis with leading research institutions in the USA. We simply cannot offer people the salaries or research funds that are offered, for example, by the Howard Hughes Medical Institute or by many of the leading US universities. What we can do is create a research community in which people want to work. And there are aspects of EMBL, such as the excitement of collaboration, the openness and the youth, which are very attractive. They make EMBL competitive in attracting people moving into their first independent position. Another area in which we cannot compete with the larger European or US universities is when dealing with the so-called two-body problem. We often see excellent candidates for a particular position who want to work somewhere where their spouse can also be employed, either in the same town or in the same institute. EMBL is simply not large enough and does not have the capacity to be competitive in these situations. We have started discussions with the DKFZ [German Centre for Cancer Research], the University of Heidelberg and other local scientific organisations to see whether we can work together to deal with this problem.

...it is very important that all research organizations are involved to some degree in a dialogue with the public

ER: When taxpayers fund research, they usually want to see something beneficial being produced. Do you see certain expectations from EMBL member states, such as juste retour, reflected in the distribution of staff?

IM: My experience as a Programme Coordinator and Scientific Director of EMBL is that the member states are very mature in their thinking about juste retour. They want to make sure that we are not excluding particular member states from our activities. However, if you look at this over a period of 10–15 years, it is clear that EMBL is open to people from all member states, and that scientists at different levels from all member states—PhD students, post-docs, group leaders, team leaders and senior scientists—have come to EMBL in a proportion that largely reflects the size of the scientific community in their home countries.. The member states want us to continue to select on the basis of scientific merit rather than on the basis of nationality.

ER: How do you deal with the political and social expectations?

IM: I think public expectations are justified. In any field of research, one has to consider why the public is funding the research. One of the pillars of western society since the Enlightenment has been the pursuit of knowledge, which is something of value to society and its development. However, in the life sciences, we are in an age in which many discoveries also have relevance to the pharmaceutical industry, medicine or biotechnology. It is necessary to demonstrate that good basic research is a motor for innovation. For this reason, and to ensure that the public can benefit from our discoveries, EMBL will continue to be active in technology transfer. Also, EMBL as a whole should collaborate more with clinicians. There are many people within the Laboratory whose research is relevant to medical problems, and we need to find ways to develop contacts and partnerships with clinical institutions. We have started to do this in a small way with the Molecular Medicine Partnership with the medical faculty of the University of Heidelberg. The EMBL–Monterotondo Mouse Biology Unit also focuses on problems of medical relevance and the head of that outstation, Nadia Rosenthal, is in the process of building better connections with clinical research institutes. This is something we need to pursue and increase in the next ten years.

ER: Along with the Molecular Medicine Partnership, EMBL has links to industry through some of its Core Facilities and its technology transfer affiliate, EMBLEM. How do you ensure that EMBL does not stray too far into applied research?

IM: EMBL has a tradition of technology development, and has recently excelled in the fields of light microscopy and software. Not too long ago, EMBL was the site of major improvements in biological mass spectrometry. I think that this is appropriate. In fact, recent technology development is enabling biology to progress at a rate that has not been seen since the development of recombinant DNA cloning strategies. I think EMBL should be engaged in technology development, but we should only develop technology that is driven by our research interests.

ER: And in the area of clinical research?

IM: EMBL is not a hospital, and it's not connected to a hospital. In principle, I see no reason why EMBL researchers should not or cannot be involved in such research on a collaborative basis with clinicians and I will continue to encourage this.

It's only by being in direct contact with research projects that one retains a sense of reality about what can be achieved and expected

ER: Former EMBL Director General Fotis C. Kafatos began a range of outreach activities, such as teacher training and EMBL's Science and Society Programme. How important is public outreach for research institutes?

IM: This relates to your question of public accountability but it reaches further. I think it is very important that all research organizations are involved to some degree in a dialogue with the public. This is not just to inform the public about what is done and what researchers are interested in. Researchers also need to know what the public thinks, what they are concerned about and what they don't want researchers to do. Furthermore, in order to maintain a top-quality research community, it's essential to reverse the disinterest in science and technology among school children. I think that all research organizations should be involved in this.

ER: Isn't this the responsibility of schools?

IM: Of course schools have to be engaged in this. But school teachers, if they don't have contact with research institutions, will find it difficult to know how research is done and what the goals, aims and motivations of researchers are. Research institutions and researchers cannot encourage this interest without working together with teachers, so if teachers want to engage their students by making contact with researchers, then I think this can only be positive.

ER: As Director General of EMBL, you have an increasingly political position. How comfortable are you with that role?

IM: I am somebody who has benefited enormously from coming to EMBL and I owe an enormous debt to the Laboratory. I am not naturally a political person, but I am prepared to work very hard to ensure that EMBL continues to flourish and that people can come here as young researchers, as I did, and develop their research within an outstanding environment. I think EMBL has to interact well with its member states and with the EC. I'm very happy to become involved in these activities and to represent EMBL, and its goals and strategies, in order to maintain support for what I see as an extremely important scientific institution.

ER: Do you still have time for your research group?

IM: That is something I worry about. My own research group has always been very central to my thinking. It was already difficult as Scientific Director to devote as much time as I would have liked to my group. That won't become easier as Director General. I sincerely hope I will have sufficient time for the people in the group and to think about my own research, because that's a necessity for someone who is in charge of a research institute. It's only by being in direct contact with research projects that one retains a sense of reality about what can be achieved and expected and what the best way to pursue research goals is. I don't want to lose touch with these realities.

ER: Dr Mattaj, thank you for the interview.