Thursday, April 10, 2014

Open source drug discovery in India

Here is an article in Forbes magazine that evaluates India's Open Source Drug Discovery programme, six years after it was founded. Started by India's Council for Scientific and Industrial Research (CSIR), the OSDD initiative is designed to focus on diseases of the developing world, such as tuberculosis and malaria. Those afflicted by such diseases are often too poor to pay for treatment, making drug development in these areas a financially unattractive proposition for pharma companies. Indeed, AstraZeneca Labs, one of the few companies in India that was working on TB and malaria, shut down its Bangalore-based R&D unit and halted all early-stage research efforts in these areas.

OSDD, as the name suggests, is intended to function as a not-for-profit, government-funded, open source platform integrating drug discovery efforts across academia, government institutes and private companies. All projects and research results are reported and collated on a web-based platform, allowing for greater collaboration between groups. In a previous discussion on Derek Lowe's blog In the Pipeline (which I also blogged about here), OSDD was mentioned as an example of innovative approaches to drug discovery that a country like India can adopt.

But as the Forbes article points out, the OSDD approach is not without its own pitfalls. The first and foremost is the limited talent pool of drug-discovery scientists available in India. This becomes a problem when there aren't enough trained people in fields like cheminformatics, who can carry out the kind of virtual screening and SAR analysis needed in the critical early stages of drug discovery. OSDD is trying to bridge the gap by creating training programmes for students and developing their own cheminformatics algorithms with help from other groups, such as the UK's Royal Society of Chemistry.

Medicinal chemistry is the second area where there aren't enough experienced scientists in academia. Most medicinal chemists tend to gain experience as they work in large pharma companies. This is a talent pool that OSDD is finding it hard to access. Firstly, as OSDD head Dr. T.S. Balganesh points out, he can't match the incentives that industry offers - "The only incentive OSDD can give them is emotional - I  can't give them high salaries or glamour", he says. Secondly, researchers who are part of OSDD work in research groups scattered throughout the country, which makes it hard to foster the kind of close collaborations that are needed for training new recruits. Says Bheemarao Ugarkar, a former AstraZeneca India employee who is now a principal investigator for medicinal chemistry at OSDD, "A lot of the training in the industry happens in a group environment with biologists, computational chemists, synthetic chemists, etc. sitting in one room day in and day out, discussing the project."

Although the OSDD uses open-access compound libraries for their analyses, investigators believe that real drug-like compounds can only be found if they prevail upon big pharma to make their compound libraries public. This is where India's troublesome intellectual property environment comes into play. Companies may be reluctant to hand over such databases knowing that they may stand to make no profit whatsoever if one of their compounds is ultimately developed into a drug.

But the biggest hurdle that OSDD needs to surmount is probably the same one that any such initiative anywhere in the world would need to overcome: What's in it for academia? Developing a cancer drug to treat humans is infinitely more complex than publishing a paper about a compound that kills cancer cells in vitro and shrinks mouse tumours. The publish-or-perish mentality that exists in academic institutions today heavily favours the latter approach. An investigator who decided to put in a good 15 or 20 years to come up with a market-ready drug would find herself out of academia long before she accomplished that goal.

OSDD has had some successes, such as generating the annotated genome of Mycobacterium tuberculosis through a collaborative platform called Connect2Decode. Although their methodology came under fire from some researchers, the results were eventually published in peer-reviewed journals. While OSDD doesn't yet have any internally-generated molecules ready for clinical trials, they have received approval to conduct clinical trials on a promising TB molecule, PA 824, which was developed elsewhere.

However, some people still believe that drug discovery is too complex a problem to be solved by an open-source approach. Probably the most realistic assessment of OSDD comes from the consultancy firm Frost and Sullivan's Jayant Singh. His take is that OSDD will serve more as a training ground for drug discovery professionals, who can then transition to the private sector.
Just creating a strong research ecosystem is “a good endpoint”, Singh says. “After all, that is the role of the government: To act as a facilitator, not a provider.”
 I think that initiatives like OSDD are laudable, and a much-needed attempt to start transforming the drug discovery ecosystem in India. We need to build collaborative, inter-disciplinary groups that can bridge the academia-industry divide and allow for free sharing of knowledge and experience. But as it stands, do I think OSDD can produce a new drug molecule within the next 5 years? I'm afraid the answer is no.

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