New Delhi: In what could be a significant step forward for discovering new drug candidates for serious, but neglected diseases, the Council of Scientific and Industrial Research (CSIR) will on Monday unveil the most detailed map yet of a pathogen’s genome.
The map of Mycobacterium tuberculosis (MTB), the organism which infects one-third of the world’s population, and kills at least 330,000 per year in India alone, will allow researchers across the world to better understand the bacterium and possibly be a model for mapping and studying other disease causing organisms.
Akin to a Google map, or a Wikipedia article that can be modified and continually updated to accommodate new geographical features or information, the MTB map will list information on the nearly 4,000 genes that determine how the bacterium lives and infects human beings.
Though scientists have mapped several organisms from yeast to humans, culling all the information known about constituent genes in one place is among the holy grails of biology, being an extensively time consuming and expensive exercise.
Step forward: A file photo of CSIR director general Samir Brahmachari. Ramesh Pathania/Mint
“The MTB would be some kind of a template. Though you can’t really compare it to the human genome which has many more genes and hence requires more labour, this effort is among the best so far,” said Hiroaki Kitano, director of the Systems Biology Institute, Tokyo.
The MTB map will be hosted on a Web portal custom developed by Infosys Technologies Ltd, that uses an emerging format called Web 3.0. This format allows users to get better search results, when querying for data. “It’s the first time such a Web service is available for scientists. You can ask questions like you ask another human being. So, you can actually ask the Web what happens when x gene interacts with y gene, and expect valid answers,” said Vinod Scaria, a scientist at the Institute of Genomics and Integrative Biology and a key OSDD expert.
Also read 7 December story -- “Infosys partnering CSIR for TB project”
Despite the seriousness of India’s TB problem, inadequate funds and a paucity of concerted research have crippled new drug discovery. CSIR’s Open Source DrugDiscovery (OSDD), first reported by Mint on 7 December, aims to find new drug candidates by first collating all known information on thedifferent genes that make up the bacterium on single web portal.
Though the MTB genome was completely sequenced in 1998, meaning scientists knew the DNA (deoxyribonucleic acid) alphabets that made up the organism’s genes, less than 40% of these genes were deciphered or, in scientist jargon, annotated.
“As of today we’ve annotated nearly 98% of the MTB. That concludes a major phase of the OSDD project and is a big step forward for science,” said Samir Brahmachari, director general of CSIR.
OSDD has been centrally funded to the tune of Rs150 crore of which Rs46 crore has been released.
However, those involved in the process said all of the progress achieved yet is largely due to people working for free.
“Over 300 students, many of them non-biologists have contributed to the bulk of the project. The money will begin to be spent on trials and experiments once we identify really promising drug targets,” said Zakir Thomas, technical head, OSDD.
The current drug discovery process, in which scientists develop molecules to activate or inactivate proteins key to an infection, is inefficient, said experts.
Most molecules that promise success in animal studies and theoretical calculations turn out to be unworkable due to surprise side effects or ineffectiveness among certain populations.
Millions of dollars are wasted as drug companies usually discover these shortcomings during the clinical trial stages.
“There aren’t enough, good toxicology models available to judge the accuracy of a drug in the initial stages. So, for every successful drug there are several that have failed and that’s what pushes up the cost of drugs,” said Chandrasekhar Nair, founder director, Bigtec Pvt. Ltd—a Bangalore-based company that makes diagnostic devices—in an earlier interview.