Daniel Louvard, Director of the Curie Institute in Paris, visited NCBS last month to sign a Memorandum of Understanding (MoU) between the Curie and NCBS. We managed to 'steal' him away from the commotion and badgered him with questions about the MoU, the new opportunities it might give to the students of NCBS and his views on current cancer research.

Supriya: How did this collaboration come about?

Daniel: Ludger Johannes had a number of interactions with several groups here, from your institute, NCBS, and they came to the idea we should formalize our interaction. So, a year ago, a year and half ago, Ludger came to my office and said it would be good if we can formalize that by a document that really reinforces our interaction, and I say, that's a good idea. So this is how the collaboration came about. This is a document that really confirms formally an existing collaboration between groups and so there's a clear understanding of what we are doing together.

Dinesh: Within the next one or two years, what do you foresee as likely interactions between the two institutes? (For example: exchange students/post-docs, workshops and courses, summer schools, research projects)

Daniel: You gave an example of exchange students and postdocs, which is pretty obvious. We have Indian people in the institute, as postdocs and graduate students. And then, you listed workshops, courses, summer schools. I think this is something we should do. I mentioned in my presentation that we organize international courses, in the Curie Institute in Paris. So, there are two possibilities. We can have a course that is organised with the staff here who are interested to do something with us, let's say something with physicists and cell biologists, and this could happen in Paris or here. One other thing I would suggest is, we can actually take advantage of this initiative, by organizing something like what we do with another institute, which is the Weizmann Institute in Israel, where a similar type of multidisciplinary culture exists. We could think about organising a symposium where delegations of people from NCBS would come to Curie and vice versa.

Dinesh: So, having a hospital and research institute in the same campus opens up projects that can take advantage of the interaction. So will there be projects based on that?

Daniel: Yeah, this is, that's one advantage we have, under the same umbrella, under the same organization we have the hospital and research, and we are very close together. But you see, for the scientist to work with a clinician, it's never easy, it takes time. Because, if you are a clinician, even if you are interested in research as a clinician, you know the patient is the priority, and so for the clinician the time scale is different from the scientist. And there is also a big difference between a clinician and a scientist; in terms of what do they want to do. We scientists, we want to understand how it works. It's a very different attitude, because we know science will never end, but for clinicians, they have to provide an immediate answer. Sometimes scientists like to do a project on perfection and beauty of science, but a clinician doesn't care about that, what he cares about is a good diagnostic even if it's not elegant from the point of view of science. So for scientists and clinicians to develop a project together, you have to take that into consideration. It’s not that easy and it’s a long process of talking to each other. But we can do it and it's of course something one has to learn. When I did my PhD, the science those days did not provide an quick answer to a medical problem. Today, with the better technology repertoire, science can actually provide answers in the short term, say, 5 years to 10 years, which is long in a way but not so long.

Dinesh: Yeah, 2 PhD's time

Daniel: Yeah, you see, when I was doing my PhD, we had absolutely no objective that the work would actually be translated into something, into reality. But today young people are in a very different context. You should believe that your science can lead to the solution to a certain problem, a biomedical problem.

Supriya: In cancer research, what is the optimal balance between fundamental and cancer specific research?

Daniel: The balance is the scientist should not sacrifice, should not say 'I am going to cure cancer'; the scientist should address a scientific question with scientific means and approaches and scientific methods. In learning more about basic fundamental principles you will provide the tools, you will provide the knowledge to answer specific questions. It's a process that goes from basic research to the hospital. But, the clinician should be involved because they know the problem and the question that should be addressed. They know that the solution to certain problem may not be explainable or elegant but they have a medical solution, so we have to get feedback from the clinician. So, it's a process that goes from science to the hospital and vice versa. Dialogue between people who have different agenda is essential. So it should be reversible back and forth and at the same time highly dynamic. The best of the clinicians know that the solution will come from understanding better the biology that we call biology of cancer, cancer biology.

Daniel: I like the way you put the question because cancer is not a single problem, there are different cancers even within cancers: breast cancer, colon cancer, prostate cancer. They are all different diseases. When you define disease in molecular terms by genetic analysis, genomic analysis you find different classes and subclasses. For instance, in breast cancer the women who have breast cancer are missing three major receptors for which we have targeted therapy. Targeted therapy kills cells depending on the presence of a particular receptor. This is in contrast to chemotherapy where you want to kill a cell that divides, that's why it has lot of secondary effects. This is brute force approach. We have reached an era where it's no longer the brute force approach and we take advantage of the the understanding of the mutation.

I see two major breakthroughs in cancer research:

One breakthrough is called personalized medicine. You have a cancer patient, you analyze the tumor, you do a complete genome sequencing or one can select 1000 genes of interest and say here is a mutation and by bioinformatics and system biology approach, say here is a defect and we can predict that giving this drug will hit that particular target, this will stop tumor growth and put that (cell) into apoptosis. If the patient has reoccurrence of the disease you reanalyze the tumor and see progression of other mutations and then you give another treatment.

Second is the understanding of the fact that tumors arise from a particular cell type, which is very often a cell that behaves like a stem cell. When we treat a patient today or develop the drugs, these drugs have been tested on animals or cells or on patients and what you look for as an endpoint is that the tumor shrinks. But the tumor arises from a sub-population of cells that are like stem cell, they are the cells that initiate the tumor and they represent 1-2% of the mass. So the tumor shrinks, but you kill the most abundant cell in tumor and you may not have killed the original cell, which behaves like stem cells. These stem cells are extremely resistant, so the assay we have to develop is to look at - when we develop drugs, do we kill these tumor stem cells? If we don't kill them, they would regrow! I believe in the future we must develop a drug that kills these tumor stem cells and not the normal cells. Then we could use these drugs that kill the tumor stem cell together with the drug that kills the rest of the tumor. Tumor in a way is an organism within an organism, it has its own program but it is not a program that we like!

So these would be the two major breakthroughs in cancer, in the future cancer would be treated case by case as a chronic disease.

Supriya: Finally, what are your impressions of NCBS?

Daniel: It's my first visit to NCBS it has fulfilled what I had expected, what people had said that NCBS is a fantastic place in India where science is very good. I was impressed by student talks and the quality of the environment and equipment here. The new building is beautiful, well conceived, the open (lab) space is fantastic and if you are in inter-disciplinary research it has to be like that! I think you are in lucky situation!