Genome Analytics Is An Indian Sunrise Opportunity? Better late Than Never?: Genomics Is Informatics.
By Ram Ramanujam, Founder-President & CEO, Propinquity Therapeutics, Bangalore, India.
Renato Dulbecco and others in America conceptualized the human genome project in 1984, with Ari Petrinos of DOE getting into the act of proposing a massive project of the size of the moon landing in 1988. Later James Watson headed the Human Genome project in the United States, followed by Francis Collins. In 1998 with Craig Venter started Celera Genomics human genome sequencing as a rival to a public project which was privately funded.
The rest is history, followed by a draft sequence of the Human genome in 2000 and a finished sequence in 2003. In 2022, all gaps filled T2T genome project gave the full picture of the human genome sequence. Still today in India, we don’t have a reference genome that requires sequencing of at least 100k genomes of Indians in a multiethnic / Multicultural society of ours. The point I am making is in 2002, Sanger.
Institute published a paper on DNA as a computing problem.
https://www.theguardian.com/technology/2008/feb/28/research.computing
In the last 50 years, India has become a powerhouse of informatics and information systems. It
was in 1997 Dr V N Balaji started Monsanto Bioinformatics and carried on to DSQ Biotech and Jubilant Biosys; the author was the first employee of DSQ Biotech Bioinformatics in 2000.Asia’s forerunner in Bioinformatics which developed as Jubilant Biosys Discovery services
later. Yet, since the late 90s, we have been struggling in Bioinformatics and Genome informatics even though academicians like Dr. Ashok Kolasker, former VC Pune Univ, excelled in Bioinformatics.
Further, in 2012, complete genomics was acquired by BGI, Shenzen a late shoe factory made into Genomics Powerhouse. When they bought Complete Genomics with VC money, they did not buy a product but a strategy. None had no idea that Covid would emerge in 2020. Having said that, why was Beijing powerful in Genomics, and what are the criteria that they have laid out in Genomics? If you ask key questions, it throws some interesting answers. Genomics is paramount to National Security.
When CRISPR technologies arrived, everyone was cautioned it could be used as Bioweapon, including CIA USA. Genomics India did not see it as a national security issue. But Beijing saw potential national assets in Genomics. In 2012, Francis Collins visited India, Bangalore IISc, and claimed Genomics is informatics and DNA is a computing problem. He elevated the somber moods of the Indian elite to think about India’s prowess in mathematics, statistics, and now IT. Genomics is informatics, Leroy Hood contends now and then in international fora.
I had the privilege of working with pioneers in Genomics across the globe and Dr JC Perez, who were tall giants in Fractals and Biomathematics. We also had the privilege of associating with Dr. Sergey Petoukhov, Russian Science Academy Laureate and professor in Moscow. Science had no boundaries. We advanced the topic of Fractal Genomics way back in 2012 in India, but there were no movers and shakers in the field in India at that time. We have been at it for 11 years and still have not given up.
This piece is written from an angle of why Genomics is informatics and how India can take advantage of Mathematics and Informatics Prowess.
Historically India did not participate in human genome sequencing, which was an international effort and consortium. However, in 2022 when full genome sequences are available in visible numbers, and Oncogenomics is emerging as a well-sought-after need for diagnostics and therapeutics, genomics should be viewed as informatics. Our SW companies are merely serving masters some services. Their huge bank balances are unutilized now except for serving shareholder value. With huge kitty, these SW firms should venture into buying IP assets in Genome Informatics and build a strategy like BGI.
For BGI-Complete Genomics, not only that Complete Genomics did not offer a product or a business model – but it neared bankruptcy precisely because the product was not ready (the sequencing instrument was way too big and overly expensive) – and the business model (of sequencing and analyzing data) came to a standstill, and the company had to be disbanded – or sold. BGI (with a rising Chinese economy behind it) was brilliant in seizing the strategy of investing in a key science-technology. (They worked out the product by miniaturizing and cheapening the technology, and the business model that DNA data analysis is done best by Affordable SW Developers).
BGI was motivated to buy Intellectual Property (US patent) of Complete Genomics since owning a US patent in sequencing enabled them to litigate Illumina (the top manufacturer of the World) – and thus gain priceless insight into “know-how” of American science and technologies. Eric Lander claimed, “Mr. President, the genome is fractal” – and put fractals into use in Foundation Medicine, circumventing the patents. Access to all knowledge can be unlocked by owning US patents, based on which they would be compelled to reveal their technologies.
In this regard, I would like to point out BGI has a statue of Dr. Radhe Drmanac Serbian scientist who made complete genomics technology thrive and discoverer of Human Genome Sequencing technology which complete genomics developed (personal communications from Dr. Andras J Pellionisz, HolgenTech Inc). As I told the BGI bought into strategy, not a business model. Visionary China made Genomics, and rival China bought It in scores. They built an asset class for the future, and now, without even knowing emerging infectious threats like COVID, they can cash in.
We, on the other hand, are reactive; they were proactive. Our Healthcare spending does not match any of the developed economies or China. The National security issue was further highlighted by the Biden administration barring BGI from procurement from the USA. Genomics is a clear national security issue, and Our Population dynamics and sequence information should stay with us and not be distributed.
It is time that we build our reference genome and prepare diagnostics and therapeutics by conducting clinical trials in Indian populations rather than outsourcing for cheap costs or cutting corners. I am not averse to sequencing in a few critical samples, but the majority should be avoided. We have no idea who is outsourcing presently and at what costs, but it should be avoided in any way. In-house and Indian sequencing and homegrown Indian companies should be given a chance and preference.
SW companies will likely have to look at this sector as Reliance took a stake in Strand Life Sciences recently. It is the movers and shakers of Indian origin who have to take the lead. Furthermore, if IP assets can be built over some time, SW companies can develop SW in scores for Western peers in Genomics. With the emergence of Ai ML and NLP in the mainstream and fractals and Biomathematics in the background, I would strongly urge Indian SW companies to enter Genome Informatics. Having said that, SW companies which have started Bioinformatics in 2000 year were predominantly unsuccessful due to their services model being similar to IT services. One thing for sure they did not realize at that time was domain knowledge required was intensive in this area. IT companies that served healthcare and Pharma companies in clinical trials data management and Pharmacovigilance thought Bioinformatics was a similar service opportunity.
Biology is context-dependent knowledge. It takes any scientist 20 years post his Ph.D. to become a proven researcher. The domain the knowledge that SW companies like Satyam Computers and TCS which started at that time, were misled by the fact there was no ready services market in this sector like other Verticals like BFSI or Retail. The domain knowledge in Molecular Biology and Genomics is not easy for a SW engineer to master and be a developer in this area. Still, you need to be a Computer scientist who has mastered the computation.
This Genome informatics also requires High-Performance computing, deep computing, and now mostly Ai ML. On the contrary, Indian Genomics companies pursuing Genome Informatics are small except for a few who don’t have the real deep pockets to invest in product development or Service offerings to MNC Pharma companies and Biotechs abroad. Few have real capabilities to do large-scale genome analysis or have computing powers.
The business models pursued already by Indian SW companies are unviable. Looking for services in this sector is futile. Rather, they should pursue product portfolio and IP assets building and SW development. The author had some experience in offering Cloud computing services for years in an IT setting, but it did not take on in an Indian setting. The author also spent four years in an Indian MNC SW setting trying to offer services in the USA, but to disappointment, the MNC miserably failed to woo the customers.
Lastly, India should invest heavily in Genomics in Plants, animals, humans, and bacterial and viral infectious diseases. National Security is of paramount importance in protecting our sequence data information of the Indian populace. India should aim at building large databases of Indian sequenced DNA for health care and Security. Aadhar is one way of national identity, but DNA signatures should be protected legally and ethically. It’s not for distribution. My genome My DNA is mine, not public.
At the very least, I can say the funding in Genomics for start-ups is alarmingly small in India. The industry is fragmented, and Revenues don’t warrant these companies to reinvest in R&D. To create a world-class ambiance in R&D and attract FDI from developed countries, we should aim to create an ecosystem that will forge alliances internationally. The matter requires urgent attention, and rivals like China are ahead of us in this game of thrones. If Genomics is informatics, and DNA is a computing Problem, as evidenced by Sanger Institute, then only Indian SW prowess will land us into mainstream Genomics. Sequencing is a commodity, we can easily master these technologies, but informatics requires careful investments and nurture.
Let Indians roll up their sleeves and work in Genome Informatics and Information systems, and create a new sector in the thriving Bioeconomy and Indian economy, which is slated to become 7.5 trillion dollars by 2031 according to this morning’s Morgan Stanley Report Nov 2022.