Bangalore: Marking a defining moment in the pursuit of creating artificial life, scientists have shown that a bacterial cell can function with a man-made synthetic genome just as well as it does with a natural one.
After demonstrating in the last few years that it was possible to make artificial chromosomes, geneticist J. Craig Venter and his team at the institute named after him in Maryland and San Diego report in Friday’s issue of Science that when the synthetic genome was transplanted into a bacterial cell, by replacing its native genome, the cell behaved normally, making fresh proteins.
Also See The Genome Timeline (Graphic)
The analogy here is: the cell operates like computer hardware, the genome like software. Venter says his findings prove that life is “basically the result of a software process”. It took 20 scientists over 10 years and $40 million (Rs187 crore) to reach a stage where using four bottles of chemicals on a chemical synthesizer they could write the genetic code of a bacterium, M. mycoides.
S. Sridhar, a geneticist at the Institute of Genomics and Integrative Biology in Delhi, believes it’s “a crucial milestone” towards creating a synthetic organism. He thinks Venter’s group is halfway towards reaching the ultimate goal of developing synthetic life. “I wouldn’t be surprised if they reach it within the next two years,” says Sridhar.
Venter himself seems more restrained. “Having just been successful in the work to construct the first synthetic bacterial cell, the team has not yet begun work to move to different level organisms,” he wrote in an email response when Mint asked how close he was to creating the algae with Exxon Mobil Corp. that is envisaged to take carbon dioxide from the atmosphere and produce biofuel. “This is one of the directions that we will move (towards) now that we have the proof of principle that synthetic bacterial cells can be constructed.”
The whole assembly of one million base pairs of DNA happened in three steps—the shorter DNA sequences were inserted into yeast where the strings were linked together; the medium-sized strings were then inserted into E. coli, and finally inserted back into yeast. The synthetic genome of M. mycoides was then transplanted into another bacterium called M. capricolum, which “booted up” just right.
Scientists say one of the revolutionary aspects demonstrated in this research is that the initial sequence could be represented as a text file on a computer. “That is, any mutation, new genes, watermark features, etc., can be introduced in a text file, and they will make it to the destination cell,” says Mukund Thattai, biophysicist at the National Centre for Biological Sciences in Bangalore. In the last three years, Thattai has led Indian student teams to the annual synthetic biology competition—iGEM—at the Massachusetts Institute of Technology.
One of those winning teams, from the Indian Institute of Technology, in Chennai, is now being funded by a student entrepreneurship award from industry body, Association of Biotech Led Enterprises, to look at photosynthetic marine algae for biofuel.
“It’s in a very preliminary stage, nowhere near the speed and scale of Venter, but I want to prepare a team that can run the race with the rest of the world,” says Shrikumar Suryanarayan, chief executive of Biotechnology-Science Cluster, Faridabad. He is mentoring the team as he believes India needs to find its own micro-organism-derived source of biofuel.
Once this technique becomes routine, the sky is the limit for applications, say scientists. Venter is also working with drug maker Novartis AG to use the technology to produce flu vaccines as he believes the process could reduce production time by 99%.
While this could turn out to be a dream tool for scientists, some worry it might remain the preserve of a few sophisticated institutes, particularly because, as early movers, Venter’s company Synthetic Genomics Inc. owns several patents. Thattai thinks otherwise—it now amounts to some technical/engineering issues, which, if resolved, could make this more widely available.
“We believe that this powerful technology does indeed have the promise of being widely used for many positive applications, such as clean water. The only way it will make an impact is if the science and technology can be (made) broadly available and used,” says Venter. But his caution about “wise” use of this tool remains paramount.
To his credit, Venter has been driving several ethical, policy and societal discussions, even creating awareness about the inbuilt safety mechanism. Scientists can insert “suicide genes” in the artificial genome so that it doesn’t survive outside the desired environment, be it a lab or a bio-reactor.
Graphic by Navin Kumar Saini / Mint
Jacob P. Koshy in New Delhi contributed to this story.