Bangalore, April 27, 2006: Is it possible to guide the movement of bacteria on a solid surface using external stimuli? Can cells be tweaked genetically to have an early warning system to alert them to a biological stress, say ultra violet light? Can cell cycles, which are notorious for going haywire after a few generations, be kept in a synchronized state for long? The answer to all the above could be yes if a set of students at the National Centre for Biological Sciences in Bangalore succeed in engineering biology to make E Coli behave as humans want them to. At least their innovative ‘biological machine’ design looks workable in theory. Moreover, several others around the world will be attempting equally innovative designs this summer.

 

Students from 39 schools worldwide kick-start the fourth annual International Genetically Engineered Machine contest in May at Massachusetts Institute of Technology in Cambridge. India is participating for the first time with three designs and leading the team is a faculty member at NCBS, Mr Mukund Thattai, a physicist by training and a biologist by passion. The six-month long synthetic biology initiative at respective institutions will culminate in a global contest in November.

 

This indeed is generating excitement among the participants in Bangalore. But the hosts are no less enthused. “I view India's participation in iGEM 2006 as a great step forward in promoting the responsible and cooperative worldwide development of future biological technologies,” said Prof Drew Endy of MIT, one of the leading synthetic biologists in the world. But for Thattai, who has closely collaborated with Endy and others and who recently started a course in synthetic biology at NCBS, the big picture lies in training an entire generation of students who are ready to do things never done before and cut across boundaries of biology and engineering.

 

“The idea is to use existing biology to the greatest possible extent and only make small modifications,” he said. We’ll do better if we try to answer a biological question, he explained, and not try to solve the traveling salesman problem using living cells. “Bacteria are not likely to replace your desktop computer anytime soon; however, they are likely to help us deliver drugs in precise timed doses to specific cells in our bodies,” noted Thattai.

 

Synthetic biology is a new research movement, pioneered by a group of researchers at MIT, University of California at Berkeley and Harvard. Researchers set out with the primary aim of doing for biological molecules what electronics did for electrons. And sticking to the initial goal, teams at MIT and elsewhere are developing biological equivalents of transistors, capacitors, resistors, and the panoply of tools needed to make biology modular. MIT also maintains a public registry of bio-parts, which can be used by any synthetic biologist build new biological devices.

 

But the field’s real appeal came to the fore when one of its champions, Jay Keasling of UC Berkeley published in Nature in April 2006 that his group was successful in re-programming yeast to produce a precursor to the anti-malarial drug artemesinin. They argued that if the modified cells could be scaled up to industrial-sized batches, they could successfully produce the drug in a far more cost effective manner vis-à-vis its extraction from plants, which are currently the only source of the drug.

 

Some success stories are already visible. In 2005, Craig Venter, the famous scientist-turned entrepreneur set up Synthetic Genomics to use synthetic biology to produce alternative fuel like ethanol and hydrogen. He had earlier announced that he was successful in producing a self-replicating virus in just two weeks. Venter is also designing a simple synthetic microorganism that could consume unnaturally large amounts of carbon dioxide.

 

The industry is not far behind as many start-ups in the US, including Codon Devices and Synthetic Genomics, have managed to get venture funding.

 

Not many are denying that synthetic biology could change the way we will generate energy, manufacture pharmaceuticals, materials and even our computers in years to come. But now is the time when the crucial issues of regulation, standardization, intellectual property, etc. need to be addressed. And addressed they be fast at regional levels too if countries like India wish to leapfrog into solving their problems in healthcare, agriculture, biotechnology and environment.

 

Synthetic biology has drawn from the open source movement in software by placing all its basic tools in the public domain. Justifiably so because the rapidly increasing scale and complexity of biology cannot be handled by hoarding information. “Because we ourselves, and nature around us, depend utterly on biology, we need to make certain that future biological technologies are developed openly and are overwhelmingly applied for constructive purposes,” Endy told BioSpectrum.

 

India is delicately poised to either welcome or shun the new advances in biology. It can continue ostrich-like, adapting to data-driven biology’s demands at a glacial pace or it can prepare to train its young biologists to think, work and innovate like engineers and mathematicians. One of the participants at NCBS course, Prof Guhan Jayaraman of biochemical and bioprocess engineering at IIT Madras, is worried that Indian scientific institutions are stuck in the slow lane.

 

“The ‘new biology’ requires bioinformatics and mathematical modeling skills to analyze whole sets of networks (metabolic, protein-interaction, signaling etc.), environmental and genetic effects on network behavior and the effect of entire networks and their interactions on cellular phenomena,” Prof Jayaraman explains. This, he says, will enable scientists to simulate biological phenomena more accurately, validate experimental data and re-construct /manipulate entire networks instead of single genes.

 

Conversely, physicists and engineers in India are unaware of the advances in biology. “They do not know that they possess the requisite skills to transform biology (or at least understand Systems Biology better than traditional biologists), if only they chose to read and understand the fundamentals of molecular and cell biology,” argued Prof Jayaraman.

 

Both Jayaraman and Thattai are planning to offer this course next year in their respective institutions on a bigger, better and customized scale. Other institutes around the country are welcome to join. The first batch at NCBS attracted researchers from General Electric who wanted to learn how to bring biological thinking to their microfabricated devices, and programmers from Strand LifeSciences who wished to learn to model disease progression. Bangalore Genei has made clones for the designs that students are tinkering with. “In this sense, the workshop is a catalyst for bigger things: while the participants watch the design groups pursue very concrete goals, they might start to discuss items of broader interest,” rued Thattai. 

 

Learning from open source movement in software, institutions can lay down a framework for encouraging open source biology in India. It’s true biology is different from software. The resources, time and effort required to innovate in biology are larger but the cost of innovation is falling as we move towards lab-on-a-chip era. Besides, India’s imperatives are no less: giant corporations hold most of the patents in agriculture, biotechnology, and pharmaceuticals. Unless India learns to innovate fast to address the country’s needs, it could well become a melting pot of orphan diseases and food insecurities.

 

Synthetic biologists are trying to self-regulate this field before it really takes off in a big way. Indian scientific community too could gather collective wisdom to formulate some regulation ‑ how to monitor and track the process to ensure that science is not abused? What are the most beneficial applications? Anyone designing a system with synthetic biology parts first need to obtain a license?

 

“This requires us to have a dialogue about open-source ideas, how to keep knowledge in the public sphere, while still allowing researchers to profit from their work. I would like to have a functional license by this summer,” said Thattai.

 

The simplest solution, argues Mr Vishwas Devaiah of Alternative Law Forum, would be for our universities and research institutions to come together on a common platform to create a repository based on open sharing of research information and patent tools. “Given that the government and the University Grants Commission have been gunning for an IPR committee as well as on increasing collaboration with foreign universities, we need to have a clear stance on technology sharing,” he added.

 

While participants of iGEM 2006 are expecting “a few specific community-based proposals” to emerge, they are also thoughtful about how best to start educating the public about the risks and rewards. NCBS has at least initiated that process in India.