Interview with Robert Eisenman

President of the SAC

“I love kayaking” says Prof. Robert “Bob” Eisenman, answering my question on what he’s doing when not doing science: “together with my wife, we visit remote and not so remote places to experience the watery part of the world.” Our interview has just finished and now we are having a beer at the bar of the hotel. Prof. Eisenman from the Fred Hutchinson Cancer Research Center (Seattle, USA) has been telling me about his scientific dreams and I’ve been asking him to give his personal view on the CIG – as president of the SAC for over more than a decade, he’s of course in a unique position to do so –, its strengths and the challenges that might show up on the horizon in the distant or not too distant future. Interestingly, his vision on the CIG is that… but let’s wait a minute. Why not start with the beginning? Who is Bob Eisenman? 

Go West, young man. From the Big Apple…

– Prof. Eisenman, where do you come from?

RE: I grew up in New York, in The Bronx actually.

– You’re a guy from The Bronx?

RE: That’s right, I’m a guy from The Bronx, went to school and did my college years in New York.

– Did you also go to University there?

RE: Yes. At college I was enrolled as a pre-medical student and was kind of pre-programmed to become a physician. But I was also very much interested in the natural sciences – I had read a lot of books about the big scientific questions of our time, and about the history of biology and medicine – while at the same time the pre-med courses focused on getting admitted to medical school did not seem particularly exciting and failed to grasp my full attention.

– In other words, you were not entirely sure any more about becoming a medical doctor.

RE: Correct, and then – looking back on that period – something important happened: I joined a lab for a while and started to work on Protozoa, culturing them, examining their DNA… I thought it was terrific. So, at the very last minute, I dropped the idea of going to medical school and decided to apply to graduate school and study biology more deeply.

…all the way to Chicago

– What happened next?

RE: After receiving my bachelor’s degree, I moved to the University of Chicago to start my PhD training at the Department of Biophysics.

– Biophysics?

RE: Yes, I did not just want to observe cellular events but was seeking to understand them at the mechanistic level and I had the strong feeling that studying biological phenomena from a physical angle might be revealing. I wanted to grasp how things really work in biology.

– What was the topic of your research?

RE: The title of my PhD thesis was “Cellular Responses to Photodynamic Action”. The aim of the project was to understand how DNA, damaged as the result of dye-sensitized photo-autooxidation, could be repaired in a cell. How could this be accomplished? Which mechanisms were involved? Keep in mind that very little was known about DNA damage and repair in those days.

– When was this?

RE: We are talking mid-sixties: the days before lasers, recombinant DNA and the explosion in molecular biology. The American biologist H. J. Muller had already demonstrated that exposure to high energy radiation can cause genetic mutations in Drosophila – research for which he received the Nobel Prize in 1946. One of the prevailing ideas at that time was that radiation would open a window to disentangle biological mechanisms – eventually it turned out that radiation was not to be the all-encompassing means to understand biology – but nonetheless in the Biophysics department there was a fruitful cross-pollination between biology and physics. So, while working on my PhD, I was exposed to thinking not only in cellular biology but in statistical mechanics, optics and dynamics as well.

Crossing the Atlantic

– You did a post-doc, I assume?

RE: Yes indeed. Heidi Diggelmann, who had been a postdoctoral fellow in Biophysics in Chicago, had accepted a position as group leader at the ISREC in Lausanne: an institute that was populating itself with young scientists at that time. She invited me to join her team and so, in 1971 I crossed the Atlantic with my wife and son to start a postdoc in Lausanne.

– On which topic?

RE: Those were the days that will be remembered as the dawn of retrovirology. David Baltimore and Howard Martin Temin had just demonstrated that the retroviral genome encodes a reverse transcriptase, enabling the synthesis of a DNA copy upon an RNA template. This led to an explosion of research in this new field…

– … and forcing Francis Crick to add another arrow to his central dogma.

RE: I think he argued that the arrow was already there, but not taken seriously.

– And suddenly you found yourself on the cutting edge of science.

RE: That’s right. Needless to say, I was all excited about it. In the Diggelmann lab at ISREC, I started to work together with another postdoc, Volker Vogt, who had begun studying the synthesis and assembly of retroviral core proteins. We figured out that these core proteins are produced as a large precursor poly-peptide that is proteolytically cleaved into separate proteins that assemble the core particle. This turned out to be a mechanism used by nearly all retroviruses.

Research from the Eisenman group

– Prof. Eisenman, in a nutshell, which scientific questions are you presently trying to answer?

RE: Over the years, we proceeded from unravelling the mechanisms of retroviral assembly to trying to understand how a retrovirus can transform a normal cell into a neoplastic state. As you know, retroviral DNA becomes incorporated into the host genome, sometimes capturing cellular genes known as oncogenes – often mutated and/or expressed at high levels in an infected cell – which are involved in a wide range of human cancers. So, retroviruses and their oncogenes had lured me into entering the field of cancer genetics. For the past 20 – 30 years, we have been focusing on the Myc family of proto-oncogenes: a family of transcription factors that regulate broad programs of gene expression with pleiotropic effects on cell growth, cell division and cell death. As such, the Myc family plays a central role in tumorigenesis.

– Is clinical application a drive for doing this kind of research?

RE: Over the past decade, as our research has evolved from studying the basic mechanisms to understanding how the network functions in normal and neoplastic cell behaviour, we have become more cognizant of ways that our work might have clinical relevance. We are still performing basic research, but our efforts are directed towards revealing vulnerabilities in this network of Myc-driven interactions which might eventually be exploited in clinical practice…

– …maybe opening new therapeutic avenues?

RE: We are hopeful.

The CIG comes into the picture

– How did you become connected with the Scientific Advisory Committee of the CIG?

RE: I had been on the ISREC advisory board as of the late 90´s; hence I was already scientifically present in the Lausanne area, knowing a lot of people there and visiting frequently. But when ISREC became part of the EPFL the advisory board was changed. So, at one time point, I found myself thinking ruefully: “Well, I will probably not see too much of Lausanne anymore in the future…”

– But how wrong you were…

RE: Indeed, when Nouria Hernandez – whom I had known since her Cold Spring Harbor years – became director of the CIG, she invited me to join the Scientific Advisory Committee of the CIG. I agreed immediately. That´s how it all started.

The SAC: a heterogeneous group of renowned scientists

– What is the function of the SAC?

RE: The purpose of the SAC is to provide advice to the CIG. The advisory board is made up of scientists from primarily European institutions, having different scientific backgrounds…

– …which is of course what you want.

RE: Absolutely. One could say that each SAC member brings a unique perspective to their review of the CIG and the challenges it faces. This diversity of backgrounds, opinions and ideas among the SAC members has turned out to be a good strategy for offering advice to the CIG which is itself scientifically diverse, as you know.

 – Scientific challenges? Non-scientific challenges?

RE: As a matter of fact, both aspects are part of the SAC’s responsibility. Considering the scientific aspect, it means that the research programme of the principal investigators – be it newcomers or established group leaders – is being reviewed and commented on at regular intervals. SAC members attend scientific presentations by the PIs, discuss their work at length and – along with an evaluation of their latest publications – try to comment constructively on their research projects.

– In other words, the SAC judges the quality of the science that is being produced at the CIG.

RE: Yes, in a manner that is largely independent of institutional entanglements. And I believe this to be particularly important for institutes predominantly focused on academic research, where teaching is not the major goal. No institute has unlimited space or unlimited funding, you know, and the quality of the research should be reviewed on a regular basis to ensure that science remains at the forefront. It is particularly important that the SAC review process is strongly supported by the CIG faculty and administration – a sure sign of a first-class institute having the confidence that it is performing first-class research.

– You also mentioned non-scientific issues being part of the SAC’s responsibility.

RE: Yes, we not only meet with the faculty, but we also talk to students, postdocs, administration and staff to discuss their needs and current concerns. The SAC can often act as a mediator between the staff, the students and the administration of the CIG. Another thing I believe to be important is that – given that the CIG is a unique entity within the much larger University of Lausanne – we can function as an interface between the CIG and the university administration. As such, we also have conversations with the dean and the rector, presently Nouria Hernandez, who of course knows the institute inside out, being a former director.

– If I understand you correctly, the SAC can provide advice on a wide array of issues.

RE: Correct. And you know, one the great things – I cannot stress this enough and it is one of the reasons why I keep coming back to Lausanne – is that the CIG actually pays attention to what we suggest: in the past, they have made quite a few changes following our advice.

– The SAC is not just there for window dressing.

RE: By no means! And what I really like is the sincere willingness of the CIG to make things better for their employees. It is very rewarding for us, SAC members, being able to contribute to this vision and helping to make the CIG a great place to work.

Transparency: not an idle word at the CIG

– Professor, as president of the SAC over the past 12 years, you have been in a unique position to witness changes at the CIG. According to you, what has changed – be it at the scientific or not so scientific level – over the past decade?

RE: I’ve seen the CIG evolve into a very diverse research environment, where scientists from different fields influence and inspire each other. From the very beginning, the institute was committed to high-quality science in a fairly focused area of research, but over time – as new groups with distinct areas of expertise were acquired, and the impact of its publications became more evident – the CIG steadily expanded its scientific horizons and increased its ability to attract additional highly qualified independent researchers, PhD students and postdocs. In parallel, the CIG has become increasingly transparent in the manner in which it is run.

– Please explain.

RE: First of all, the CIG is by no means a hierarchical place. There is no single personality high up, overseeing all research programmes – unlike other scientific institutes, which are often hierarchically organized. Quite on the contrary, I sense a strong feeling of equality and collegiality among members of the institute, where everyone can have his or her say. People seem to speak their minds freely and feel listened to: a tradition that the current director, Alexandre Reymond, has maintained.

Challenges for the future?

– What are the challenges the CIG is facing for the future?

RE: One of the main challenges is to be aware of the rapidly shifting directions into which the life sciences are heading – frequently linked to important technological and conceptual advances – and be able to respond and contribute to such developments.

– Find out where research is going to?

RE: Precisely. This doesn´t mean that every new trend needs to be followed, but it’s important not to become siloed and to be aware of new technologies and concepts that show up on the scientific horizon and their potential impact on the ongoing research at the CIG. It basically means to keep one´s finger on the pulse of scientific developments and looking ahead. In other words, I believe the paradigm to be a rather straightforward one: trust your judgement and hire highly qualified scientists, producing exciting science.

– How would you like to see the CIG evolve in the future?

RE: That is a difficult question. I believe there are two aspects which need to be considered: on the one hand, the research environment and secondly the purely scientific point of view. Considering the first aspect, a vision for the future would be to have an institute where people feel secure and free to follow their curiosity and where researchers from different disciplines stimulate and inspire each other. The CIG already approximates such a place and some pride is certainly justified. The problem will be to maintain such an environment amongst the myriad stresses and constant demands being raised. In terms of the scientific questions being addressed, I think that continuing to actively encourage diversity among the research groups and their approaches, as currently practiced at the CIG, is really a promising way to face the challenges for the future: the past teaches us that there is no sure way to foresee the future but being flexible will no doubt be critical. Another aspect in this context would be to continue developing ways to reach out to the public. In order to maintain strong support for creative unbiased investigation, the public needs to be aware that fundamental research is an investment in the future: creating knowledge, where immediate goals are not as important as the conviction that you are developing a unique body of scientific wisdom that somehow, somewhere, sometime will be beneficial for our world.

– Professor Eisenman, thank you so much for this interview.

RE: It’s been a pleasure.

Ronny Leemans