iGEM: A springboard for diving into synbio

TCS: An IT Pioneer

Today, TCS is an established global leader in the IT world.  As a young “digital” recruit into TCS, I look forward to contributing to the growth of this great firm.  To my mind, the sustained success of TCS shapes not only the destiny of the Tata Group but also the future of India.  On reflection, I find it truly extraordinary that TCS was founded just three years after Gordon Moore published his now famous article predicting the exponential growth in compute.

This brief note is to draw your kind attention to a much faster and more disruptive revolution in biology.

TCS: A Leader in Life Sciences Operations

Recently, the Everest Group ranked TCS as a leader in Life Sciences Operations.  I understand that the top companies in the Life Sciences rely on TCS for implementing successful digital transformations.  My seniors from SASTRA University who are in TCS R&I roles also share their excitement of working with TCS researchers to build powerful platforms for pharmaco-vigilance and drug discovery, based on sound software engineering and the application of cutting-edge genomic research.

What is Synthetic Biology?

Synthetic biology is an emerging discipline that enables the design and engineering of novel biological systems, verily, Nature 2.0.   It has brought engineering rigour and scalability to biotechnology in three ways:

1. Standardised “biological parts”
2. Artificial gene synthesis
3. Universal experimental methods including test protocols

For example, earlier this year, my team and I designed, developed, debugged, and deposited in an international open repository, six DNA and RNA parts for early detection of cervical cancer.

Cell-Free Systems

All organisms are made of cells.  The information flow in a cell happens through DNA, RNA and proteins in that order.  Cell-free (protein) expression systems remove the unnecessary cellular overhead such as cell organelles, cytoplasm and cell membranes.  Instead, they retain only essential enzymes, amino acids, and ribosomes required for the synthesis of desired proteins.  We tested our six novel biological parts using a cell-free expression kit sponsored by New England Biolabs.  In essence, the new cell-free expression technologies are lighter and more efficient entities than cells.  They also blur the boundaries between biology and chemistry.

Engineering Biology

Such stunning successes in SynBio are made possible by the application of computational principles and tools to develop a new ‘engineerable’ biology.  Research is driven by an iterative design-build-test-learn cycle.  Thus, any project in this emerging industry is invariably based on four steps:

1. design phase - mathematical modelling and computational design of biological parts
2. build phase -  in vitro synthesis and assembly of the parts
3. test phase - wet lab experimentation
4. learn phase - analysis of experiments, redesign, and possible prototyping.

SynBio is already disrupting several industries including food, energy, materials, agriculture, healthcare including diagnostics and therapeutics, textiles and fashion, information storage and even computing.  TCS has several prominent customers in each of these industries.  Much as Industry 4.0 is built on IoT and automation, the SynBio revolution is powered by interdisciplinary paradigms.  It is enabling the production of hitherto ‘impossible’ products through innovative and planet-friendly processes; Impossible Burger to wit.  Genetically re-purposed platforms (chassis) are becoming efficient and scalable for products ranging from human breast milk to engineered spider silk.

Scientists can not only create replicas of life itself but engineer novel life forms.  For example,  Twist Biosciences, a leading SynBio company, has synthesised, de novo, key segments of the new Wuhan Coronavirus genome.  Using this, some research groups claim to have now developed functional vaccines for the Coronavirus in less than four days.  This is an astonishing achievement made possible because of open access to the genome sequence.

Custom-designed, artificially synthesised DNA has become a commodity that may be ordered online.  Powerful sequencing devices are only slightly bigger than USB sticks.  Scientists have been routinely sequencing genomes in the middle of remote jungles.  Wet lab experiments can be done on the cloud with the assistance of robots.  Today, one can read, write, and edit biological code (perhaps) more easily than one wrote, and ran computer code fifty years ago in India.

TCS Paves the Way

As I read The TCS Story by Mr. S. Ramadorai, I marvelled at the steep obstacles that the leaders of TCS had to overcome in the early days of the IT industry.  Interestingly, SynBio leaders in the West have internalised the best practices of Silicon Valley, and adapted the ability to experiment, and scale.  IndieBio is one example that successfully emulates the incubator model.

An Approach to Nurture Nature 2.0

I believe that the wonders of SynBio are replicable in and scalable from India.  We can not afford to miss the SynBio revolution that is underway.  This revolution will disrupt agriculture, pharmaceuticals, energy, information storage, diagnostics, and many others.  TCS leads digital transformation from India.  Thanks to the pioneers like TCS, none of the legacy obstacles exist now.  To my mind, the only missing ingredient for a SynBio revolution in India is talent.  May I share an approach to spot and nurture the talent needed for the Nature 2.0 revolution.

What is iGEM?

The iGEM competition (International Genetically Engineered Machine) grew out of MIT’s early efforts in Systems Biology in 2003.  In the last fifteen years, it has shaped the direction of SynBio education, research, and entrepreneurship.  For example, leading SynBio companies such as Ginkgo Bioworks have emerged from the iGEM competition.

iGEM’s main goals are to improve tools for engineering biology and manage the open Registry of Standard Biological Parts.  The iGEM competition in 2019 attracted over 6,000 students from all over the world. The competition is driven by a set of strong processes and passionate volunteers.  A significant portion is driven by digital platforms that encourage active learning, sharing, and collaboration.  For example, to be considered for the competition, we uploaded the genetic sequences of all our six novel biological parts, after rigorous experimental characterisation.

Leveraging the iGEM Process

In 2019, I led the first iGEM team from SASTRA University.  We won a Silver Award and nominated for Best Software.  The team from EPFL, Switzerland, won the Grand Prize.  Their project was very similar to ours but they had gone further and developed a paper-based sensor for disease detection in vineyards.  However, ours was the only few among 350 teams to apply Machine Learning techniques.

As a team leader, I observed with keen interest the “iGEM model” of motivating several thousand young students across the world to work in teams, raise funds, and do substantial amounts of additional yet original academic research.  Furthermore, their processes ensured significant stakeholder consultation, and actively promoted periodic professional reviews.  On top of the data-driven approach driving the scientific rigour, there was an additional emphasis on proactive collaboration.  An unforgiving timeline to deliver results was the icing on the cake.

Seventeen Indian teams began the iGEM-2019, but only ten Indian teams completed the iGEM marathon successfully. In contrast, there were 150+ teams from China!  In total, about 200 Indian students with skills in computational biology, web development, biotechnology and biological engineering of systems participated in 2019.  The best SynBio talent with practical experience is to be found in the iGEM community.

However, both the quantum and quality of Indian participation in iGEM has significant room to grow.  One of the major difficulties faced by Indian iGEM teams is the uncertainty around funding.  TCS could leverage the iGEM process, and underwrite the Indian teams for, say, five years.

Synthetic biology is truly fascinating and is bound to bring about a paradigm shift in the way we think about life and more...