Globally, the Human Genome Sequencing Initiative is seen as a significant project that worked on the open source model. It worked on the success of Linux, which enabled a free flow of information between researchers. There is also the Tropical Disease Initiative (TDI) of the University of California, San Francisco. By means of an open source research and development model, it will look for treatments for dengue, sleeping sickness, leishmaniasis. TDI seeks to unite the attempts of hundreds of volunteer researchers from around the world, centering on the purpose of computational biology and chemistry on drug innovation. Discoveries resulting from this research would not be patented; instead, they would be made available to so-called virtual pharma. However, TDI has not yet finalised the details of its intellectual property model.
Closer home, the trigger for this new form of drug discovery has been initiated by a Council for Scientific and Industrial Research (CSIR)-led Insilico biology consortium, involving leading institutes such as Institute of Genomics and Integrative Biology (IGIB), Institute of Microbial Technology (IMT), Central Drug Research Institute (CDRI), National Institute of Immunology (NII), Vallabhbhai Patel Chest Institute (VPCI), Delhi University. They will later be joined by institutes such as Indian Institutes of Technology (IIT), Centre for Cellular and Molecular Biology (CCMB), Indian Institute of Science and others. Armed with a sizeable grant from the government, CSIR is finalising the broad contours of the project titled Open Source Drug Discovery (OSDD).
But, what would open-source drug discovery look like Says a senior government official involved with the project: As with current software collaborations, we plan to have a website by the end of March, where researchers could search and annotate shared databases. Individual pages would host tasks such as searching for new targets, finding chemicals to attack known targets, and posting data from related chemistry and biology experiments. He adds, The key to the projects success is that any discovery would be off patent. An open-source license would keep all discoveries freely available to researchers andeventuallyto drug makers. The absence of patents, and the use of volunteer staff, would contain the costs of drug development.
Typically, the project would start with identifying the gene that needs to be targeted, screening thousands of chemical molecules that could potentially work, researching their efficacy, testing them first on animals and, subsequently, on human beings. Finally, launching the drug in the market would come under the ambit of drug companies.
Basically, the concept is intended to provide all the tools and training required for drug discovery till the insilico experimentations (computing-based experimentation). Thereafter, clever mechanisms are being worked out that harness the productivity of the various government and university laboratories to continue with the drug discovery process, including the wet experimentations, till the final molecule is identified after clinical trials. This concept will also take care of the issue of lack of human resources by generating more scientists who have the skills for modern drug discovery.
The era of collaborative R&D has been initiated in the country, informs CSIR director-general Samir K Brahmachari, adding that a pilot project will be kicked off in March on Tuberculosis bacilli. Co-development of projects through open source reduces cost as well as the time taken for discovery as many minds would be working together for novel targets, he says.
Before we predict how the interested parties in drug discovery will benefit from new open-source products that address their needs with increased flexibility, it would be worthwhile to take stock of the prevailing drug discovery scenario. As per the available estimates for the developed countries, the cost of discovering a single drug molecule and its further development representing a journey from mind to market place, ranges between Rs 1,000-2,000 crore and takes about 10-12 years. Further, commercial success of a drug is somewhat uncertain. The rate of success can be as low as 1%.
In India, the cost of discovering a drug could be as low as Rs 140-200 crore. Therefore, development can move forward only with an open source model, as research in drug design is an expensive and time consuming activity, says Surojit Bose, founder and director of an IIT Delhi start-up called LeadInvent Technologies. Life science development is mostly an outcome of academic research and passing the baton as an open source ensures that the technology does not limits itself in the thesis paper, he adds.
Presently, the available financial resources for funding drug research include in-house R&D inputs by drug companies, government funding through publicly funded R&D institutions and promotion funds set up by the government, as well as a special new drug development fund operated by the department of science and technology. However, the present level of R&D is quite low as compared to most of the developed countries. The present level of spend on R&D (about 5% of turnover) is much lower as compared to most of the developed countries (15-20%).
Says PS Ramkumar, co-founder and director, Digital Integrated Health Exchange, although industry has accepted many open source-based products into mainstream, it is more prevalent among academia than the industry. A hybrid model, wherein the R&D is outsourced by companies to the open source community and the productisation is done by the industry, looks like a win-win from a cost-risk-speed perspective and equitable revenue sharing, he adds.
On its part, the department of biotechnology (DBT) is doing its bit to promote the open source drug discovery initiative in the country. DBT advisor Madhan Mohan says, We provide financial support to various institutions for open source software development activities. These resources are made available on their respective websites as well as in the form of mirror sites.
One such mirror site established at IMT Chandigarh (a CSIR laboratory) provides a large number of software packages to the scientific community all over the globe. Similar mirror sites are being established at CDFD, Hyderabad, IISc, Bangalore, JNU, New Delhi, MKU, Madurai and Pune University, Pune. The super computing facility for bioinformatics activities established at IIT, Delhi has developed several useful softwares like gene to drug, made available in open access format.
Analysts claim that open source has to be relevant for the drug companies for research purposes, which is being done at various academic institutions in collaboration with various universities and agencies. The open source should also be available in such a way that it gives the flexibility to access the code, modify it, improve it, and use the software in any way and many more areas to be well defined before accepting open source, explains Sandeep Sinha, industry manager, healthcare practice, Frost & Sullivan, South Asia & Middle East.
The traditional ecosystem and methodology of drug discovery is highly dependent on large corporations and are solely driven by the profit motive. Open source research is inexpensive, shared, and creates alternatives to monopolistic proprietary patents. It gives people access to the tools they need to innovate for themselves, says Utkarsh Palnitkar, industry leader health sciences, Ernst & Young. If scientists worldwide support a collective research effort, new innovations would crop up and existing ones fine-tuned, just as programmers everywhere are constantly sending fixes and upgrades to Linux and other open-source software programs, he adds.
Jaijit Bhattacharya, country director (government strategy), Sun Microsystems India, says, We see that most of the efforts on drug discovery are towards lifestyle diseases, rather than the far deadlier tropical diseases. We feel that OSDD is an extremely brilliant concept that can help in marshaling the collective energies of young scientists for drug discovery for the devastating tropical diseases such as TB, Chikungunya, malaria, Kala-azar etc.
He suggests a revenue model too. Creating an internet- based open source of information to be utilised by the drug companies at a nominal license fee in order to produce affordable drugs for neglected diseases of the poor, says Bhattacharya. Open source drug discovery would have independent biologists freely sharing their work through the internet.
All discoveries would remain in the public domain, and final stages of drug development would be conducted by whatever company offered the lowest bid. Since the key information related to the drugs action would not be patented, generic competitors could immediately enter the market, keeping the drug prices low.
It seems that open source, which has swept through many areas of computing in recent years, could provide a fillip to the drug discovery efforts of the Indian research community as well.