Design, synthesis, assembly and transplantation of synthetic chromosomes will no longer be impossible with synthetic biology

The magazine New Scientist asked the genome scientist J Craig Venter in 2007: “assuming you can make synthetic bacteria, what will you do with them?” Venter replied: “over the next 20 years, synthetic genomics is going to become standard for making anything. The chemical industry will depend on it. Hopefully a large part of the energy industry will depend on it. We really need to find an alternative to taking carbon out of the ground, burning it and putting it into the atmosphere. This is the single biggest contribution I could make”.

Bold words, coming from a rebel scientist — one who created a storm over a decade ago by first trying to patent a human gene (not allowed to do so by law), and then decoding the entire human genome, in competition with the publicly funded organizations doing the same. Now, he and his group have gone ahead and done what New Scientist had “assumed”.

On the 20{+t}{+h} of May this year, Venter and colleagues made scientific history by chemically synthesizing the total genetic material (or genome) of a microbe called M. mycoides, and introducing it into the cell of another microbe, M. capricolum in a manner that the transplanted synthetic genome of mycoides is given total and sole control of the host capricolum cell.

What was the result? The capricolum cells divided quite well and grew in number generation after generation, producing the protein material coded by the mycoides genome. In about 20-40 generations, the cells would end up producing nothing else but the material dictated by the chemically synthesized genome of M. mycoides. A new age of synthetic biology has been ushered by Venter.

What bodes for the future? If one can synthesize genomes in the lab, introduce them into recipient cells and “express” their protein products, why not produce biofuels, may be ask microbes to produce food by photosynthesis or whatever? As the authors write in their paper in Science, “If the methods described here can be generalized, design, synthesis, assembly and transplantation of synthetic chromosomes will no longer be a barrier to the progress of synthetic biology”.

Microsoft of synthetic biology?

What are the ethical and sociological implications of the work? Elizabeth Pennisi who wrote a commentary on the work in the same issue of Science quotes the anthropologist Paul Rabinow, who says “this experiment will certainly reconfigure the ethical imagination”, and the MIT social scientist Kenneth Oye as: “Right now, we are shooting in the dark as to what the long-term benefits and long-term risks will be…As even more “artificial” life comes into reach, regulatory agencies will need to establish the proper regulations in a timely fashion” – since the possibility of misuse unfortunately exists.

There is the other issue of patents and ownership. Venter's group has applied for several patents covering the work.

While one group, commenting on this, worries whether it could result in a monopoly on “synthetic life”, another sounds a reassuring note: “It is unlikely that Synthetic Genomics (Venter's company) will become the Microsoft of synthetic biology”.

Some worry whether such chemical creations of genome would lead to Frankensteinism — wherein a person creates a destructive agency that goes out of control, ruining the person himself. Indeed, the UK-based covered the Venter experiment as: “maverick Frankenstein scientist Dr. Craig Venter creates “artificial life”.

Did they create artificial life?

Well, they synthesized the genome of mycoides and transplanted it into the living cell of capricolum in a manner that the genome of the latter was disabled. Some have called it ‘rebooting' the genetic software of one organism into another organism, akin to taking a computer operating with Microsoft software and rebooting it with Linux.

It is more than that, explains Dr. J Gowrishankar of CDFD. He points out that the ‘rebooted' capricolum cells still had their “hardware” at first.

But as these cells divide to generate new daughter cells, a process of “infinite dilution” occurs with each generation; by about the 30th generation, even the hardware is replaced by that instructed by the synthetic genome put in by Venter.

The cells now are alive with the genes, proteins, lipids and all other molecules dictated by this synthetic genome.

What other hidden messages did this synthetic genome have?

When I was a child, I used to see my father take a special ink and mark his shirts before he sent them to the washerman. He called them as identification watermarks. Venter and group too put in watermarks in their synthetic genome — not with ink but with sequences of bases in the DNA.

These contain the researchers' names, email IDs, and also chosen quotations from literature. He has challenged readers to decode and email him and his colleagues (Dr Gowrishankar too has asked his students to decode these watermark sequences). While I will not divulge the names and emails, I shall divulge some of the quotations.

True to his reputation as a rebel, Venter chose to quote the words of the rebel Irish writer James Joyce, which appear as the title of this article. And from the book called American Prometheus (biography of J. Robert Oppenheimer): “See things not as they are, but as they might be”. And from Richard Feynman, who said: “What I cannot build, I cannot understand”. How apt!

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