Drug Discovery, Open-Source Style

By Allison Proffitt

January 26, 2010
| ‘We are putting into practice the philosophy of open-source software: that given enough eyeballs, all bugs are shallow.” So says Zakir Thomas, project director of Open Source Drug Discovery, or OSDD. Established in India, OSDD has established a novel open-source platform for both computational and experimental technologies to make drug discovery for infectious and neglected diseases cost effective and affordable to the people of the developing world.

Launched in September 2008, the organization attracted more than 2000 participants last year. The initiative is the brain child of Samir Brahmachari, director general of India’s Council of Scientific and Industrial Research (CSIR) and a dominant figure in Indian science. Brahmachari’s philosophy that when it comes to health, we need to have a balanced view between health as a right and health as a business.

The New Delhi-based OSDD is funded by a commitment of $38 million from the Indian government explains Thomas, a CSIR staff member. Even with steady financial support, Thomas admits that managing OSDD is challenging. “Managing a project in open source is much more complex than managing a normal project within a conventional environment, say in a pharmaceutical set up or elsewhere,” he says. “Because there is a close monitoring and reporting mechanism and all traditional management is available. OSDD is a very different model… We have researchers actually participating. We have researchers actually collaborating, doing work, but there is no corporate structure in the traditional sense.” 

The 2000-plus members of OSDD are students, scientists, academic institutions, and companies worldwide. Membership is open to anyone, and members are assigned credits based on their level of involvement and contribution. Members can choose to be sponsors (though it’s not required) and commit to giving either funds or to sharing resources.

The community interacts on OSDD’s collaborative online platform exploiting web 2.0 technologies for exchange of ideas, data and resources. “This is exactly how it works,” explains Thomas: “If you have a problem, you post it online and the community members then look at it and they give their suggestions for how to take things forward.”

Tackling TB
The first target toward which OSDD is turning its sights is tuberculosis, recently called an “orphan giant” in an editorial in Nature. TB has a particularly high incidence of mortality in India.

“The front line drugs that are used now [to treat TB] are the ones that came out in the ‘50s and ‘60s,” explains Thomas. “My first belief is that it’s not funding that is lacking as far as TB is concerned, but it is science that is lacking.” OSDD is working hard to combat that problem.

Thomas acknowledges that TB is a very small market in terms of profitability, and it is risky. “It’s very unlikely that [pharma] will invest their money into clinical trials even if they have promising leads,” he says. So OSDD has made a worldwide offer: if any organization has a molecule with potential but is reluctant to take it into the clinic, “we are willing to fund it and take it through clinical trials.”

The beauty of open source, Thomas points out, is that research can proceed along parallel tracks. The offer to take on any un-pursued compounds has met with immediate response from two academic institutions in India. OSDD researchers are also searching for targets themselves. OSDD has just launched a program for comprehensive (re)annotation of the Mycobacterium tuberculosis (MTb) genome. Anshu Bhardwaj calls it one of the “biggest collaborative efforts” that’s been done on TB.

Despite countless publications, there is little available TB data in the curated databases. “There is no single point where you can actually go and find out what is the work to date on [MTb],” explains Bhardwaj. “This is very important because if you really want a drug on MTb, you should understand the bacteria fully so you can actually design a better drug.”

OSDD partnered with the Systems Biology Institute Japan and has Japanese, Indian, and U.S. volunteer students to work on the annotation project. Bhardwaj along with Vinod Scaria posted the project on the OSDD platform hoping for 150 students and researchers. “In two days we got over 200 participants,” she says. “That is the power of the project.” That number has since soared to 800 volunteers. To ensure quality, these student volunteers are coordinated by faculty volunteers from their respective institutions who in turn work under the guidance of principal investigators.

The results so far are encouraging. The group has created Tbrowse, an open-source genome browser with a million data points from nearly fifty different resources in the standard Generic Feature Format (GFF). Bhardwaj has already done a pilot study as a proof-of-concept that virtual collaboration can succeed in challenging scientific projects by annotating 600 genes in six months through online collaboration and interaction. The next step is to annotate all of MTb’s 4000 genes, she says. Step two is to use the data to understand how things work inside the bacterium.

OSDD is committed to releasing any eventual drugs with “no IP encumbrances,” says Thomas. “It can be manufactured by any drug manufacturer in the world without taking permissions.” Although the market for TB is small, the medical need is huge, and Thomas is confident that an effective drug will be produced by the generic drug industry. 

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