WILLIAM REVILLE
The recent announcement by American scientist Craig Venter that he had made a “synthetic cell” naturally generated widespread attention. Comments such as “revolutionary breakthrough” vied for attention with “scientist plays God”.
However, the truth is that Venter has achieved a significant technical feat that is also of philosophical importance, but no more. Specifically, he copied the genome (genetic make-up) of a bacterium in the laboratory and inserted the copy into another bacterium, where it successfully took over the running of the host cell. Scientifically this is what would be expected to happen, but it had not been practically demonstrated before. Venter’s proof of principle is a first step on a very long road towards the construction of new useful organisms radically different from the spectrum of organisms that, undisturbed, nature has produced. There are, however, more conventional, and probably faster, ways to achieve this end.
Venter did not create life – he copied life, and his entire method depends on pre-existing living cells. So, far from “playing God”, Venter is not even on the same playing field as God.
Venter made a copy in the laboratory of the genetic material present in the bacterium M mycoides.This genetic material is built into a structure called the chromosome. Chemically the chromosome is made of a long string of units called nucleotides. There are four different nucleotides denoted by the letters A, T, G and C. The genetic information is coded in the sequence of these letters along the length of the chromosome. There are 1.08 million letters in the M mycoideschromosome and Venter worked out their sequence in previous experiments.
You can buy bottles of the pure individual nucleotides (A,T,G,C) from chemical supply companies and you can chemically string them together, in lengths up to several hundred nucleotides long, in any sequence you like using a machine called a DNA synthesiser. In this way Venter first copied the entire M mycoideschromosome piecemeal in individual 1,000-long nucleotide segments. He then gradually linked these segments together in the right order until he eventually had an exact copy of the entire M mycoides1.08 million nucleotide long chromosome. He then inserted this chromosome into another bacterium M capricolum where it took over and ran the cell as the bacterium M mycoides.
Every step of this procedure depends on pre-existing life. Firstly, the nucleotides (A,T,G,C) fed into the DNA synthesiser were either extracted from living cells or were synthesised using catalysts called enzymes extracted from living cells.
Secondly, the higher order stitching together of the 1,000 long nucleotide segments of the chromosome was done by living cells – Venter inserted these segments into living yeast cells. Natural repair mechanisms in the yeast cells assumed that the inserted segments were fragmented chromosomes and “repaired” them by stitching them together. And, finally, when the copy chromosome was complete it was inserted into a living bacterial cell where it took over. This living host bacterial cell is a very complex and delicate organisation of molecular and supramolecular assemblies arranged in a precise manner, immersed in a fluid in which a complex mixture of many hundreds of chemicals are dissolved in precisely the right amounts and balance to support life, and all of this is surrounded by a delicate cell membrane.
Work will now begin, using Venter’s technique, on designing chromosomes to direct micro-organisms to do useful things. For example, Venter has been contracted by the Exxon corporation to design algae that will suck carbon dioxide out of the air and convert it into biofuel.
However, such developments will surely be very slow. It is one thing to demonstrate that a copy of a natural chromosome works as well as the original. It will be quite another matter to get a chromosome to work that never existed naturally before. The difficulty here is illustrated by the work Venter just carried out. The first copy of the chromosome Venter made failed to “boot up” the host bacterial cell when it was inserted. Careful examination showed that just one letter of the 1.08 million letters in the copy chromosome was the wrong letter. When this mistake was corrected, the copy chromosome worked! This is how delicately poised life is.
William Reville is associate prof of biochemistry and public aware- ness of science officer at UCC – understandingscience.ucc.ie