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The period between our last report and the present has seen immense changes in modern biology. Where does the National Centre for Biological Sciences see itself in this rapidly changing world? A recurring question that small laboratories in countries such as India need to ask is a simple one — are we viable? Many exciting recent developments in biology are in areas that have, for sometime now, been widely discussed amongst biologists, other scientists and the lay public. But their full implications are yet to sink in fully even amongst specialists. We have now the sequence of several important genomes which has, in turn, led to the development of areas of biology that require the analysis of large data sets. DNA sequence information has also resulted in greatly increasing the number and variety of reagents available for our research. Mutations can be made, with relative ease, in predicted genes in several model organisms. Predicted proteins can be synthesized and, most importantly, used in sensitive assays of structure and cellular-function. Some would interpret these developments to mean that research in biology will increasingly need large groups and use methods of ‘big-science’ such as those used in many areas of experimental physics. They would say that an assembly-line approach and automation would drive successful biology, that the age of the small laboratory and the active, and independent, investigator is over – once again. Many have also opined that hypothesis-driven biology is less meaningful than before and will be replaced by analyzing large masses of data to try and decipher meaningful patterns. How valid are these predictions? Answers to these are necessary to judge our own viability as scientists and also as an institution.

It is certainly true that the large-scale efforts of various kinds were necessary for some genome sequencing projects and similar efforts will be seen for even more complex projects. Global structure-function analysis by nuclear magnetic resonance or using synchrotrons, analysis of gene-and protein-expression patterns and functional genomics approaches are some areas that may require groups working together with specialists working at each step in the process. Similarly, large-scale collaborations or large research groups could certainly be well placed to use all this information effectively and in an allencompassing manner. They may well have a sweeping range of expertise and talent that small groups, or even small institutions, lack. They will have the resources and equipment to generate even more complex data and to analyze them well and in a variety of ways. The quality of such work, and we already have no shortage of examples, can be high and its output prodigious. Thus, while one can bemoan the good old days and the replacement of innovative thinking by brute force in biology, one will be completely misplaced in doing so. ‘Big biology‘ has not been less thoughtful or informative than ‘small biology’ and it cannot be wished away.

So, if there is no shortage of good ‘big biology’, what is the situation with ‘small biology’? Despite fears to the contrary, ‘small science’ in biology is alive and bubbling. In their wake, large projects have generated new opportunities for the small laboratory. Advances in microscopy, physiology and gene-expression analysis combined with the accessibility of computational approaches has allowed small groups to stay at the frontline of research. Many of the new approaches and techniques have allowed the expansion of the number of organisms that biologists can study at the mechanistic level. Comparative studies have, and continue to, reveal new molecular, cellular and organismal mechanisms. Indeed, some of the most stimulating recent intellectual advances have come from smaller groups. The understanding of the mechanisms of double-stranded RNAinterference, the developments in stem cell research and the changes in our understanding of how signaling molecules are organized and function at the cell-surface are but some of these advances.

While the fact that small research groups have and can do well is good news for a centre such as NCBS, there are some very stark dangers. Small does not necessarily mean cheap. Cottage-industry biology today can be quite expensive. Every modern investigator would like to have easy access to quality microscopy, tools for the analysis of macromolecules, gene-expression arrays etc. NCBS has been extraordinarily lucky in the range of technical talent of our faculty and their research groups, comprising largely of the principal investigator and a small number of graduate students and assistants. Together we have the expertise to manage a wide range of equipment that can be used by all of us and, indeed, we are well equipped in most areas of our work. However, we must continually upgrade our facilities and infrastructure. Small size also imposes unusual challenges on our staff. Talented investigators will always be under pressure to keep pace with changes and to continually innovate. In this situation, we require the ability to change and respond to changes outside rapidly and for this ’small‘ may be beautiful. But this also requires the ability to think and carry out one’s research with confidence and not be swept by the vagaries of fashion, for changing directions frequently will not lead to the results that come only from pursuing the long road.

It is these two issues, the generation of material resources and ways to remain innovative in a rapidly changing world of biology that I would like to address briefly.

We have, till now, two principal sources of funding. First, our infrastructure, buildings and salaries are supported, almost exclusively, by internal funds by virtue of our being a part of the Tata Institute of Fundamental Research. About half of our research support is also from the same source – largely going towards shared large-equipment. Second, our investigators have been extraordinarily successful in attracting national and international research support from government agencies, international organizations and foundations. These kinds of funding have been invaluable and must grow. But, it also is clear that many kinds of requirements cannot be met from these two traditional sources alone. We need to develop the Institute’s corpus fund of donations that will allow us to support visitors, chaired positions, travel of students etc. Such sources of support will give the flexibility and variety that traditional methods do not have. Industry also offers new opportunities, practical applications and directions that are not always accessed by support from the usual sources. We have made beginnings in these new directions of funding while continuing to strengthen and develop our usual sources. No matter what the source of funds, there is one common thread, though, that links research support today. There is no such thing as a free lunch. Every rupee, from government or industry, foreign or local, comes with its strings or restrictions – just as each comes with its peculiar advantages. A diverse source of funding assures us of having the flexibility of working in relatively expensive areas but also retaining the academic freedom of inquiry that we value so much and which drives us all. Walking tightropes without falling into restrictive traps of various kinds is the challenge. And the coming few years will tell us if and how well we manage this.

Difficult though it is to generate resources for science, this is a trivial task compared to sustaining innovation and thrust in one’s research. A small place like NCBS does not have the ballast of a large institution that anchors us in difficult times. We will be blown away very easily if we are unable to do quality work and many aspects of our employment structure make rapid recovery not easily possible. We cannot, indeed few places can, dismiss our past and start again. We must therefore be constantly innovative and do at least reasonably well. In our last report, I argued that interactions and collaborations enhance innovation. By having people of many kinds seeing each other, talking to each other and working with each other. We have, in the past two years developed many interactive programs with physicists, chemists, other biologists and social scientists. Our campus has seen a large number of colloquia, meetings and workshops and we have seen people from all over the city, from India and the world participate in these events. Our most valuable treasure is our interacting network of students, other researchers and faculty. If they get value from our meetings and find them stimulating, the relative intellectual isolation of being a biology institute will not be felt. We hope to push harder on our meetings and workshops program and develop an administrative and financial structure for it that will allow it to function effectively. Our aim is to bring, each year, the best scientists in the world to our campus to interact with students and researchers from all over the region. To do this again and again so that not only do we feel a sense of community with our peers the world over, but in the process develop a network of talent and accomplishment of which we are an actively participating component.

No matter how we try and plan to succeed and no matter how well funded we are, we are simply only as good as our research, summarized for you in this report. And this research depends critically on the regular infusion of new investigators. I conclude by welcoming our newest colleague to join our academic staff – G. V. Shivashankar. Shiva opens up an entire new area of research at NCBS that symbolizes all the promise that the future holds.

K. VijayRaghavan
NCBS Director