Chemically creating life in the laboratory
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The DNA sequence of the synthetic one is identical to the natural one
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— Photo: AFP
Ethical issue: Cloning of Dolly the sheep has not raise any outrage, but cloning a human certainly does.
“I am the family face; flesh perishes. I live on, projecting trait and trace through time to times anon, and leaping from place to place over oblivion.” So wrote Thomas Hardy in his poem ‘heredity’ describing direct descent of life from one generation to the next.
Indeed, the poem reflects the DNA in our genome. Dr Drew Endy (of MIT) quoted this when he described how people at the J. Craig Venter Institute (JCVI) bypass nature’s constraint of direct descent. Scientists there have used chemistry (and biochemistry) to produce the first synthetic genome in the laboratory.
They chemically synthesised many fragments of the DNA, encoding the 582,970-units-long genome of a bacterium called M
ycoplasma genitalium. Next, they assembled these fragments in perfect order to generate the genome of the bacterium.
The DNA sequence of the synthetic one was confirmed to be identical to the natural one. Preliminary results were first published in the 24 Jan 2008 issue of Science, and the more detailed successful one in the 5 Dec 2008 issue of PNAS (US).
The task is somewhat akin to writing phrases and sentences first, and then putting them together in proper order to make the meaningful chapter of a book.
While the DNA pieces were synthesised chemically, the stitching together was done using the biochemical machinery of a host cell. About 100 pieces of the genome, each 5000-7000 units long in DNA sequence, were first joined together to produce 25 sub-assemblies, each about 24000 base pairs long.
These were then introduced into the bacterium E. coli to produce sufficient DNA for the next steps. Next, they repeated the procedure to generate large fragments comprising 1/4th of the whole genome of M genitalium.
Now, they used the clever trick of exploiting the process called homologous recombination. This is a basic essential process in every cell, which physically rearranges the two strands of DNA.
It involves the alignment of similar sequences, is used in DNA repair and to restart replication that has been stalled or damaged. And an organism like yeast does this more efficiently, wholesale faster than bacteria like coli.
The JCVI researchers inserted the synthesised DNA fragments into yeast and utilised its homologous recombination ability to generate the whole 580,000 long genome of M genitalium in one step. As one of the authors of the paper remarked: “I am astounded by our team’s progress in assembling large DNA molecules. It remains to be seen how far we can push this yeast assembly platforms to boot up the synthetic chromosome”.
This is clearly a landmark work that leads into the brave new world of synthesising life itself in the laboratory. It was hardly 200 years ago when Friedrich Wohler synthesised urea, an organic molecule, in the chemical laboratory, thus throwing out the notion of “vital forces” involved in the components of living organisms.
25 years since
And hardly 25 years since Robert Woodward assembled the complex biological molecule vitamin B12 from ‘carbon, nitrogen and oxygen,’ Chenglu, Wang and Kung synthesized the protein insulin in the lab, Merrifield automated it, and Michelson and Todd DNA itself in the chemical lab (and companies marked DNA synthesizers).
What is the next step — making life itself in the lab, bypassing nature? With single cell organisms like M. genitalium, it might not be far away. It is now possible in the lab to do so, by inserting the genome into a ‘host’ cell and asking the latter to make the bacterium of your choice.
But this still needs a ‘live’ host, but this would soon be bypassed too. It is now technically possible to chemically assemble an artificial cell-like assembly using lipids, biochemicals and chemically synthesized proteins — everything except the DNA.
If only we find a way to insert the bacterial genome into this proto-cell, and somehow trigger it (electric pulse? ionic currents?) to make the bacterium itself!! We would have chemically created life in the lab. This is not a pipedream; JCVI scientists are already on the job, and my bet is they will do it within a few years.
Ethical issues
This surely raises ethical questions, a matter that JCVI is keenly aware of and is already engaged in with ethicists. Even their present work on M genitalium was done with prior approval of ethical experts. But then, today it is M genitalium, tomorrow it could be a more advanced, multicellular organism, and that could flummox even the ethicist.
Remember, ethics too is an evolving discipline that provides considered advice, based on contemporary analysis and consensus. Morals, on the other, are less accommodative. What is ethically acceptable might or might not be morally so. Recall the current debate on abortion, and the position that some are taking that abortion is not to be allowed even in the extreme case of threat to the mother’s life.
Assisted reproduction, which is the other side of the coin and truly a recently initiated technology, has become ethically and morally acceptable. Cloning of Dolly the sheep has not raise any outrage, but cloning a human certainly does.
In this connection, an insightful perspective was provided by a man of the cloak. When a Catholic priest was asked whether Jesus Christ should be cloned back to life from the material in the shrouds of Turin, he said: ‘yes, you will bring back the body, not his soul’. What a profoundly elevating statement of truth and wisdom!
D. BALASUBRAMANIAN
dbala@lvpei.org
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