CSIR launches open source drug discovery

The Council of Scientific and Industrial Research (CSIR) has launched an innovative 'open source drug discovery' (OSDD) programme to combat infectious diseases that afflict the developing world. OSDD is a CSIR-led consortium with global partnerships to provide affordable healthcare especially to the weaker sections of global populations.

Addressing a press conference in New Delhi, minister for science and technology and earth sciences, Kapil Sibal said that though the Open Source approach has been successfully adopted in software as also in the human genome sequencing project, it is for the first time that open source approach is being applied to drug discovery anywhere in the world.

Explaining the concept to the media, Prof. Samir K. Brahmachari, DG, CSIR termed the OSDD as a novel and path-breaking initiative.

Market forces and business acumen discourage big pharmaceutical companies from developing drugs for infectious diseases like tuberculosis (TB), malaria, etc, since such projects have long gestation period, heavy R&D costs and low success rate. Even when successful, the returns are low since these diseases generally afflict the poorer sections of the society. Thus, it would be naïve to expect drug discovery for infectious diseases to become a lucrative standard business model.

The Open source model, on the other hand, represents a viable alternate model of drug discovery for infectious diseases. It has two defining features.

• Expansion of resources by allowing open access and,
• Incentives to contribute to the co-operative effort.

In order to expand the intellectual resource and enable collaborative drug discovery, CSIR has set up a web portal http://www.osdd.net to provide data on the pathogens, tools for data analysis, and discussion forum for members to share ideas, projects for students to participate in drug discovery, etc.

CSIR has has invited everyone - students, researchers, scientists, academicians, doctors, software professionals, traditional healers or industry experts - to join the battle against infectious diseases by registering at the OSDD website and sharing their ideas.

The website is based on the Wiki (Hawaiian word for "fast") model designed to enable anyone to contribute or modify content in a collaborative mode. These ideas and suggestions will be peer- reviewed and the contributor commensurately acknowledged.

OSDD rests on three cardinal principles of collaboration, sharing and discovering. It aims to bring openness and collaborative spirit to the drug discovery process with the objective of keeping drug cost low.

Until recently, drug discovery was a ''wet'' science - if scientists wanted to identify potentially therapeutic chemicals, they had to do experiments in test tubes, and use live cultures or animals. Developments in bioinformatics have enabled researchers to do drug discovery 'in silico' - that is, by sitting in front of their computers or in ''dry'' labs.

Researchers can compare, on computers, potential disease targets against large chemical databases to identify potential drugs. The Internet encourages synergizing of the inventive spirit of a large number of researchers by uniting them in a collaborative mode for drug discovery. The laboratory experiments during this process will be carried at CSIR sponsored labs.

In the OSDD programme, a core committee of expert scientists monitors the entire process of drug discovery closely. The discovery of new potential- drugs will be in public domain thus precluding monopoly. The potential drugs will be made generic as soon as they are discovered. This will enable pharmaceutical companies to bring the medicines to the market, and yet keep drug prices competitive.

In the first phase, drugs against Tuberculosis (TB) bacillus (Mycobacterium tuberculosis), will be undertaken. This includes drugs against both drug resistant and latent tuberculosis

Why tuberculosis as the first disease target?
TB is the leading cause of death from bacterial infection. WHO reports that one-third of the world's population is currently infected with TB. The estimated incidence of TB in India is 1.8 million new cases annually with an estimated 370,000 deaths due to TB occuring each year -  over 1,000 deaths a day, or 2 TB deaths every 3 minutes.

The current TB therapy was developed in the 1960's; and no major advancement in treatment has emerged for almost half a century. Of the 1,556 new chemical entities marketed worldwide, between 1975 and 2004, only three were for TB. The presently used drugs, with standard therapeutic duration of 6-9 months, - Isoniazid, Rifampicin, Pyrazinamide and Ethambutol-- require careful monitoring if drug resistance is to be avoided.

The multidrug-resistant (MDR) TB takes longer to treat with second-line drugs, which are more expensive and have stronger side-effects. Extensively drug-resistant (XDR)-TB can develop when these second-line drugs are misused or mismanaged and available therapy therefore also become ineffective. Because XDR-TB is resistant to first- and second-line drugs, treatment options are seriously limited.

Timelines
The overall project has been sectioned into work packages, which can be broadly categorised into two phases. In Phase I (2008-2012) new chemical entities are expected to be discovered. These will be taken for preclinical and clinical trials in Phase II (2012-2017).

Incentives
To encourage students and researchers to participate, problems encountered in drug discovery process will be posted as ''Challenges'' on the OSDD website. Each problem will have a pre-determined set of credit points associated to it. The best solutions, as decided by the core committee, will be commensurately awarded.
The registered participants will be provided with colour coded membership cards. Users can upgrade the card (change colour) by providing more quality-inputs. CSIR is exploring the possibility of tying up with banks to add incentive features to the cards issued to OSDD members.

Students may also enroll online for summer projects of their choice from the list of projects hosted on the web portal. The progress of the each project will be assessed by their online project mentors. Students would also be awarded certificates to acknowledge their contributions.

Funding
In the Eleventh Plan Rs500 crore has been earmarked for OSDD and Rs150 crore ($38 million) has already been sanctioned . An equivalent amount of funding would be raised from international agencies and philanthropists. About Rs46 crore ($12 million) has been already released by the government.

Partners
In this largest ever collaborative research project on drug discovery several institutions in India including Universities, research institutes, private sector and others are participating. Global Research Alliance which comprises of governmental/non-profit organizations around the world is supporting OSDD.

CSIR-affiliated

• Institute of Genomics and Integrative Biology (IGIB), Delhi
• Institute of Microbial Technology (IMT), Chandigarh
• National Chemical Laboratory (NCL), Pune
• Indian Institute of Chemical Technology (IICT), Hyderabad
• Center for Cellular and Molecular Biology (CCMB), Hyderabad
• Central Drug Research Institute (CDRI), Lucknow
• Indian Institute of Integrative Medicine (IIIM), Jammu

Non-CSIR:

• Jawaharlal Nehru University (JNU), Delhi
• University of Saurashtra
• University of Hyderabad
• University of Delhi
• National Institute of Immunology (NII), Delhi
• Center for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad
• Bhabha Atomic Research Centre (BARC), Mumbai
• All India Institute of Medical Sciences (AIIMS), Delhi
• Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh
• Tuberculosis Research Centre (TRC), Chennai
• Indian Institute of Science (IISc), Bangalore
• Bose Institute, Kolkata
• International Centre for Genetic Engineering and Biotechnology (ICGEB), Delhi
• Industry:
• Sun Microsystems
• LeadInvent Technologies
• TCG Lifesciences
• Astra Zeneca India
• Lifecare Innovations Pvt. Ltd
• Jalaja Technologies