Open source drug discovery (OSDD) initiative of Council of Scientific and Industrial Research (CSIR), also known in industry circles as wiki-style of drug making, was widely expected to add a new dimension to design and development of medicines for neglected tropical diseases like tuberculosis (TB), malaria and leshmaniasis. Instead, as the initiative showed signs of gaining traction among the research community in recent months, a fierce discussion is raging in the public domain on the viability of the project, with concerns being raised that OSDD might fail.
Critics are allaying fears that the initiative could fail by means of inappropriate prioritisation of projects. It could also degenerate into a free-for-all bedlam. The initiative could remain stillborn if proper ways to implement focused and time-bound projects through the efforts of identified participants are not devised.
Most importantly, the drug companies, seen as the vital link to transform the research into meaningful products, are far from excited about the entire exercise. ?At best, it is a useful learning experience for research purposes. There is no sound business model in it,? seems to be their refrain.
Moreover, there is no clarity with respect to issues such as intellectual property rights (IPR) and patents arrived from the OSDD programme. ?The researched product from an open source model is bound to attract ?copycats,? thereby reducing our profit margins,? says an official from a leading pharmaceutical firm. ?Free wiki is not a feasible model for long-term business in drug discovery,? says another pharmaceutical company?s official.
?It is relatively easy for software professionals to make the transition to open source; for the researchers, it is going to be much harder. Besides, the question foremost on our minds is this: which pharmaceutical company would go for manufacturing, which has less margins. Perhaps, this can hold true for government-owned pharmaceutical units, but may not attract the private companies,? says a leading senior scientist.
A researcher involved with the OSDD programme says, ?At present, the OSDD team lacks experience in scientifically managing the project of this magnitude. Therefore, experienced scientists, along with other agencies such as the departments of biotech and science and technology should be roped in. Besides, the focus should be on drug discovery and not just developing various websites; at present, a lot of efforts are given only on website development. In addition, public-private partnerships should be encouraged and funded under the OSDD programme.?
Is the OSDD programme headed in the right direction? Is the much-touted ?Wiki? approach to drug making flawed? ?These discussions or concerns are being conducted by OSDD members who are interested in making OSDD a success,? defends Zakir Thomas, OSDD project director and head of CSIR director-general?s technical cell.
?The strength of any open source project is such open and free exchange of thoughts and ideas. These ideas exchanged by the community members would help to anticipate and avert any chance of failure. The reason why Linux and other open source software are more robust is that it is worked on by large number of contributors who form a community. The OSDD community is taking the same approach for problem solving in drug discovery,? says Thomas. He adds, ?Be that as it may, much of the concerns expressed are already addressed in OSDD.?
Few are aware but TB kills 30,00,000 people in the world every year, more than AIDS, malaria, and other tropical disease combined. In India too, TB is one of the leading causes of mortality in India?killing 2 persons every three minute, nearly 1,000 every day.
More disturbing news: There are not enough drugs in the pipeline for market release for TB in near future. Despite over 10 years of efforts by industry and R&D laboratories and the isolated efforts of individuals worldwide, not even a single new drug molecule against TB has resulted, although some are at various stages of clinical trials.
Most public-funded institutions do a lot of biomedical research, but the last mile of drug discovery is left to the pharmaceutical industry, which is essentially a ?closed-door? activity. With respect to diseases of the poor, for example, TB, where the market incentive is very small, it is not possible to convince the pharmaceutical companies to work on these drugs, says Samir K Brahmachari, director-general, CSIR.
It is was in this backdrop that the OSDD initiative of CSIR was launched last year, in anticipation that ?affordable? drugs for the underprivileged, especially for neglected diseases like TB, malaria, etc would soon be a reality. While government has committed Rs 150 crore towards this project, an equivalent amount of funding would be raised from international agencies and philanthropists. Here?s a quick rundown on the project.
Institute of Genomics and Integrative Biology (IGIB) is leading the task of ?in-silico? biology for drug target identification by using high performance computers. In this project, several algorithms and strategies have been developed with emphasis on non-toxic targets. National JALMA Institute of Leprosy and other Mycobacterial Diseases of Indian Council of Medical Research (ICMR) is providing authentic strains of Mycobacterium to the researchers for experiments. Institute of Life Sciences, a public private partnership promoted by Dr Reddy?s, University of Hyderabad and Andhra Pradesh government, has joined OSDD to participate in drug discovery. The institute has expertise in cloning, expression, and assay development, organic synthesis of small molecules, functional chemical library management and screening.
There has been international participation too. An example is Cambia of Australia whose CEO Richard Jefferson is a well known expert in the field of open approach in patents and innovation. Cambia has agreed to plot the patent landscape of Mycobacterium tuberculosis. Institute of Bioinformatics (IOB), which is a collaborative set up of Johns Hopkins University has also joined OSDD as a partner. IOB scientists create the largest community resource of experimental data in human proteins. It is a portal for sharing and integration of human protein data. They are now bringing these competencies to the OSDD project.
?As on December 30 last year, OSDD had 512 registered participants from reputed institutions like Harvard Medical School, Johns Hopkins University etc in the US and many reputed institutions in India. Internally, we had set a target of at least 500 registrations by year-end, which has been reached,? informs Thomas.
?OSDD has made tremendous progress in a short period of one year. It has not only established the technology architecture, but has also created a community of open source drug discovery scientists who are now actively posting drug related problems and are putting the progress made on those problems in the open source,? says Jaijit Bhattacharya, director?government strategy, Sun Microsystems India. He adds: ?This is snowballing into a participatory drug discovery process of massive proportions. OSDD has already contacted many biotech and pharma firms. AstraZeneca and Biocon are already actively involved. As the initiative becomes even bigger, more firms are expected to join in.?
Scientists agree that mycobacterium tuberculosis (MTB) is a complex mycobacterium. It has evaded drug discovery despite enormous scientific progress in the last 50 years. What is required is a holistic approach to understand the biology of infection to design better drugs. The complexity of this task and past experience, points to the dire need for the best minds to collaborate and share in an open environment.
Scientists note that the OSDD initiative would not turnout to be anti-corporate, but with some financial assistance from the government, it would be one of those measures to give affordable healthcare to the masses, especially drugs for TB and malaria. The public knowledge system, such as OSDD, could soon change into private profit system and as industry insiders put it, it could turn into ?a decentralised Web based community effort, where scientists from different laboratories, universities, institutes and corporations could work together for a common cause and make cheaper drugs for a host of diseases.?
?With inputs from BV Mahalakshmi