Making Open Source Drug Discovery a Reality in TB Treatment Research

"...diseases like TB with high mortality but low profitability are neglected by the current system of pharmaceutical research"
The Indian government's Open Source Drug Discovery (OSDD) initiative released the results of its 'Connect 2 Decode' (C2D) project to re-annotate the biological and genetic information relating to the Mycobacterium tuberculosis (Mtb) genome at a conference. This is the first time that a comprehensive mapping of the Mtb genome has been compiled, verified and made publicly available. C2D's findings may contain critical data to unlock previously undiscovered details of tuberculosis (TB); resulting in development opportunities for urgently needed new TB drugs in India and other developing countries. Read more

World Health Organization (WHO) reports that 1.7 million people die annually from TB and that in some areas of the world, one in four people with TB becomes ill with a form of the disease that can no longer be treated with standard drugs regimens. Despite this public health emergency, TB research funding remains alarmingly inadequate, particularly for research into new drugs.

In addition, conventional market-based patent incentives are ineffective in addressing public health needs in developing countries with only 1% of newly developed drugs targeting neglected diseases.

"We need to have a balanced view between health as a right and health as a business. It is because there has been imbalance in this view, that diseases like TB with high mortality but low profitability are neglected by the current system of pharmaceutical research," said Dr Samir K Brahmachari, scientist and Director General of the Indian organisation Council of Scientific and Industrial Research (CSIR). "As virtually no new TB drugs have been developed since the 1960s, OSDD's model in particular holds great promise for the scientific community by stimulating the development of better drugs and diagnostics for patients."

With children and people living with HIV in India and other developing countries bearing the greatest burden of the disease, as well as the emergence and spread of TB that is resistant to treatment by the standard anti-TB drugs, there is an urgent global, but unanswered, need for new drugs.

"For us the irony is that with the availability of drugs for HIV and particularly of safe and affordable Indian generics, we are living with HIV but dying of TB," Loon Gangte of the Delhi Network of Positive People, a support group of people living with HIV/AIDS, said. "TB research has yet to see any great progress as we struggle to pull ourselves out of a system that places profits before people's lives. India's OSDD project holds immense hope for my community."

Under the C2D project, researchers and students pooled their time and skills using online tools to provide insights into 4000 genes of the deadly pathogen. The researchers also mapped the genes as they relate to functional interactions and pathways. Their work is held in a shared database, which OSDD will share through a globally accessible database to any research institutions involved in TB research through its open portal (

C2D demonstrates the power of people to connect through the internet, particular young people, and accomplish complex research tasks. It is also a distinct move from a hierarchical based model of doing science towards one of equal collaboration.

OSDD was launched in September 2008 by CSIR. It is a USD 35 million (Rs 146 Crores) collaborative research effort that focuses primarily on TB. OSDD's objective is to accelerate research and development (R&D) for TB drugs. With a global community of nearly 3000 members from 74 countries, OSDD brings together scientists, doctors, students, policy experts, software professionals and others to work on TB research.

OSDD is the first project of its kind by any government.

About a decade ago, the genome sequence of Mtb was deciphered, triggering intense research on the pathogen. Along with it came the first annotation, providing the first "parts list" of the microbe. A re-annotation carried out subsequently identified a more parts, completing the list of proteins coded by the genome.

To get a systems view of the microbe, however, we need to move on from the "parts list" towards how these parts are "assembled" in the cell. To do this, the description of each part must be as complete as possible.

The first, called TBGO, has obtained associations for each gene with functional ontologies, thus getting first clues of the functions of the various proteins. Second, each protein is studied at high resolution by modeling their three dimensional structures, through which, higher order clues about their functional roles are obtained. Third, proteins which interact with various sugars or carbohydrates in the cell are deciphered; these are believed to be important for the signaling events in the cell, somewhat akin to the switches. Fourth, the assembly of the parts has been sought out by identifying those parts that talk to each other directly and those parts that talk to others through mediators, such as metabolites.

Integrating data from all the angles, or network of the parts list is reconstructed, in which functional modules (or biochemical pathways) are also identified. The network helps in understanding how metabolism takes place in the bacterial cells, how it compares with human and other bacteria and helps in answering questions about what strategies should be adopted to kill the bacteria, eventually useful for new drug discovery.

A fifth theme that has been pursued in this project is to identify proteins that contain antigenic parts in them that could trigger immune responses in the host and thus ultimately help in rational vaccine design.

The C2D project has attempted exactly this from four different angles.

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