The Neem Genome and a Public-Private-Partnership

Dr. Vijay Chandru

Friday September 30^th 2011 morning when scientists all over India scanned the newspaper while they had their “cuppa”, some caught a small headline with a picture insert that resembled the one below.

“Ganit Labs in Bangalore sequences the Neem Genome”.

The first reaction that most of us felt was a bit of a jingoistic pride – glad that a plant genome of such significance to our culture, traditional knowledge and biodiversity was decoded within India and not elsewhere. After all, the attempt by W R Grace to patent some properties of Neem, had led to the big tussle at the European Patent Office and later courts until finally the IP(intellectual property) was wrested back and the patent was revoked – an indelible saga of a green/biodiversity battle and victory of South over North.

If the scientist reading the newspapers was an aficionado of genome sequencing, she would have quickly realized that this is the first instance in India of a de novo genome assembly (as opposed to re-sequencing) of a higher organism (Eukaryote), a genome of approximately 400 megabases. The realization then probably dawned that this must have therefore been a strong inter-disciplinary effort of molecular biology and computer science. Moreover, the news announcements of the Neem Sequencing talked of a PPP (public-private –partnership or to be politically correct a people-private-partnership) called Ganit Labs that had made this success possible. How did this combination come together?

Genuine interdisciplinary teams are difficult to create in the best of places, and India has no proven record of doing this well. In 2000, a group of computer science faculty (this author included) from the Indian Institute of Science (IISc) stepped out of the comfort zone of the Mysore Maharaja’s donated estates to start a company called Strand Genomics Private Limited. India’s first example of sanctioned academic entrepreneurship was launched with IISc holding promoter shares through the special purpose vehicle of SID (Society for Innovation and Development). The premise of this venture was that biology, and genomics in particular, was entering an era in which it would surely run into an information processing barrier. By bringing the “best in class” computer science to work shoulder to shoulder with equally talented life scientists to address these challenges, the business plan laid out a path to global leadership in commercial bioinformatics. A decade later this vision has borne out and Strand has a work force of over 70 computer scientists and 50 life scientists delivering technologies to over 2000 labs worldwide with roughly 30% market share in the segment of data analytics platforms for high throughput integrated biology.

Strand has a reputation as an “in silico” company with the ability to perform miracles with big data (images, text, numerical, networks, structures) of relevance to the life sciences. The ability to access, visualise, analyse and biologically interpret the results leads to novel hypotheses and ultimately to discovery. The lacuna that Strand faced was in its inability to generate its own data – perform experiments and generate an end-to-end value. The challenge was that the business model for setting up a high end functional genomics laboratory to run in India purely as a private enterprise just didn’t exist. This was a perfect case for a PPP initiative and several attempts to create a PPP model and enthuse government agencies traditionally funding research biology and biotechnology ran into a brick wall.

The success with the proposal finally came about as a partnership with the Institute for Bioinformatics and Applied Biotechnology - a small, agile and not-for-profit institute led by the senior structural biologist Professor N Yathindra and funded by the State Government of Karnataka. The primary funding agency turned out to be the Department of Informatics (DIT/MCIT) which had a small fund allocated for “BioIT” and the State Government pitched in with a partial matching grant. DIT had well informed bureaucrats in charge who accepted our thesis that genomics presented the perfect example of the fourth paradigm of science – data intensive science that would restrict success to only those who took the data bull by the horns. No amount of smart or elegant physics would find the laws to get past these challenges. DIT also understood through the analogy of the electronics boom – that the time to invest in high throughput genomics was dictated by the remarkable phenomenon of exponentially dropping costs and increasing speed of processing. In electronics we call it Moore’s law after Gordon Moore of Intel Corp. and in genome sequencing we could call it Cantor’s Law (after Professor Charles Cantor of Sequenom and Boston University). Cantor’s law states that the cost of genome sequencing is halving about every six months since 2006 and that eventually the cost of sequencing a complete human genome will settle at about Rs 5,000. Incidentally, JASON (the intellectual heirs of the Manhattan Project who continue to advise the US Government and Military on emerging technologies) has predicted that Whole Human Genome Sequencing will hit the $100 mark in 2013.

The endorsement of Strand by the Technical Advisory Committee provided the credibility and after a year of persistent follow up, the funds became available. The potential for seeding young entrepreneurs who would take to the BioIT sector as a consequence of exposure to Ganit Labs was the clincher. The Government of Karnataka gave a partial matching grant, IBAB provided space, infrastructure and an eager academic partner providing students, an entrepreneurship culture and research plans for the lab. Scientific advisory support from the Centre for Human Genetics as well as the Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR) added scientific caliber. Strand was to provide the key personnel including scientific leadership for the lab, access to the software technologies needed for the lab and took responsibility for marketing the services of the lab.

At Strand we were confident of the eventual success with the proposal and recruited in early 2009 a hugely talented scientist, a PhD from Oxford, American Cancer Society Fellow at Scripps, Senior Molecular Diagnostics Researcher at Affymetrix who was eager to return to India and have a go at an entrepreneurial journey. Ganit labs turned out to be a perfect start for him in his mission to create a lab that would match Strand’s prowess in bioinformatics with high quality experimental rigour. With a passion for success and an obsession with quality and open access, Dr Binay Panda set about recruiting talent, building and commissioning the lab. Since the funds took about a year to arrive, we spent a couple of months meticulously planning the whole exercise that could be energized when the money became available. I began to get seriously worried that the talent we had assembled would unravel while “Waiting for Godot”! We even lost a young recruit who had worked for Solexa (an early sequencing platform company eventually acquired by Illumina) in Cambridge, UK. Fortunately various fixes worked in our favour.

We used this period to explore relationships with oncology centres in the city. We found enthusiastic partners in Drs. Devi Shetty, Paul Salins and Abraham (Moni) Kuriakose at the Mazumdar-Shaw Cancer Center. We recognized an opportunity to collaborate on a problem related to cancer genome for a subtype of oral cancer which had been neglected by other researchers. Dr Shetty and I took an instinctive decision to fund the pilot research project for Ganit Labs to get started with the raw sequencing being outsourced since our labs were not ready. This gave serious fillip to the morale of the team and, out of the Strand office, the Ganit team began furious work on the re-sequencing and annotation of the sequence data. The symbiotic relationship with Strand was evident with the latter concurrently building its release of the product “Avadis NGS” for exactly these type of applications. The relationship with the MSCC team has grown and we now have a joint plan for a fully integrated translational research centre in head and neck cancers.

I began writing this article to document success of a PPP model¹ – a model that is under serious threat because of civil society’s perception that this is yet another misguided priority that allows public funds to be leveraged by the private sector. I will not try to enter this debate here, but will state that there are still several challenges to be overcome by Ganit Labs in the years to come. The operations have to be break even within a couple of years; the technology is changing with a menacing speed requiring some flexibility and dexterity in use of funds with approval of the audits of the funding agencies. The next two years will be exciting and challenging.

The remarkable fact is that in less than 15 months and at an expense of roughly around Rs 20 crores, Ganit labs has been fully commissioned and currently has two whole genome and one desktop small genome sequencing machines with all the sample prep and validation technologies as well as high performance computing needed to go end-to-end as has been demonstrated with the neem genome/transcriptome² and oral cancer work³. For Ganit Labs to turn into a globally competitive Genomics Institute, we will require 4 to 5 times the current level of support for hardware and consumables. The big question is whether the public funding agencies will take such a bold step with a PPP.

Dr. Vijay Chandru is the current serving Hon. President of the Association of Biotech led Enterprises (ABLE), the apex body of the Indian biotech industry. His day job is as CEO of Strand Life Sciences, a private limited company. Chandru is also a member of the High Panel on Science and Technology for Development at UNESCO.