"India could build a world-class position in understanding how genomes work"

Richard J Feldmann, scientist and president of Global Determinants Inc.

Richard J Feldmann, scientist and president of Global Determinants Inc., was recently in India to visit his grandchildren and to give scientific talks at the University of Madras in Chennai, and at the Institute for Bioinformatics and Applied Biotechnology (IBAB) and Indian Institute of Science (IISc) in Bangalore. Feldmann, who spent his first career developing graphical techniques for modeling proteins and nucleic acids at the US National Institutes of Heal (NIH) in Bethesda, Maryland, shared his thoughts on the results of his studies of how Connectrons control the expression of genes in mouse cells.

Twenty five years ago, on his first trip to India, Feldmann spent several weeks installing software for searching crystallographic structures that he had developed on the computer at the Tata Institute of Fundamental Research (TIFR) in Mumbai. At that time, the TIFR computer was one of the few American computers in India used for doing science. Seventeen years ago in 1988, Feldmann toured India giving a scientific talk on the molecular graphic and modeling work that he had been doing. At that time he also tried to convince young Indian scientific workers to write programs for PCs that were just becoming popular. These PCs were instances of American chips in Indian computers made by Hindustan Computers Ltd (HCL). Many of the young scientific workers have now risen to prominence in Indian academia.

On this trip, Feldmann said that he has brought to India a revolutionary idea about how cells function. Six years ago, he had a fundamental insight about how RNA and DNA interact to regulate the expression of genes. He has discovered four-sequence relationships that he calls Connectrons. Connectrons occur in good numbers and in important places in the genomes of many creatures. In collaboration with workers in the Genome Science Center of RIKEN in Japan, he has taken data for the transcriptome of the mouse genome and shown how DNA that does not code for proteins - the so-called Junk DNA - plays an important role in controlling how gene expression is controlled and therefore how proteins are produced.

In the scientific talks that he gave, Feldmann hopes to build relationships with Indian scientists and bioinformaticians that will result in developing and proving the work that he has done. In addition, Feldmann hopes to focus entrepreneurial interest in developing applications that will eventually affect human health and food production.

Feldmann was awash with stories about Connectrons and how his idea could be applied to solving problems of human health. Having been exposed to malaria for the first time on his other trips, Feldmann said that he would love to understand how the genome of the malarial parasite interacts with the human genome. The difference between his earlier trips and this trip is that now the DNA sequencing of both the malarial parasite genome and the human genome have been completed. Now with a modest amount of computing, he should be able to determine how the malarial parasite imbeds itself in the human body causing so much disease and economic loss.

India's potential

Feldmann argues that India is poised on the edge of the Information Age. That India is in the process of discovering how information, which travels at the speed of light, can transform the state of human health. He argues that the different layers of cellular information - first the genome, then the transcriptome and now the Connectrome - are the most powerful types of information to emerge in the last few years. With entrepreneurial help, Feldmann argues that India could build a world-class position in understanding how genomes work, in understanding how to cure many different diseases and in producing more food.

Future of Connectrons

"The Connectron idea of expression control seems to be very powerful. In the six years since the idea first emerged, I have performed computations on many genomes ranging from the simplest prokaryotes, symbiots and the Archea through the single-celled eukaryotes to the intermediate - and large-genome higher eukaryotes such as worm, fly, human, rat and mouse.

For decades the central paradigm has been that of doing physical experiments. With the sequencing of complete genomes, it becomes possible to conduct wide-ranging computational experiments such as Connectron determination. The balance between physical and computational experimentation is shifting. My sense is that in the decades to come, scientists will first do computations that are then followed by simple physical array measurements as verification of hypotheses. Right now, patenting is hung-up on doing sample physical experiments to show the existence and utility of Connectrons. We are trying to formulate physical experiments to that end."

Control of gene expression by means of Connectrons

"The Connectrome of the transcriptome of a genome is the statement of how each transcript affects the expression of other transcripts. As such, the Connectrome is the logical vehicle for doing simulation of transcript dynamics. In order to accelerate progress in Connectromics, it seems that the time is right for establishing a database of all Connectromes on the Internet. Such a database would act as the support for doing simulations of generalized expression control in all genomes," he added.