An article in the American journal Science on December 10th, 1999, caused quite a stir, prompting media headlines such as: "Scientists soon to create life from non-living chemicals". The story died down quickly but, nevertheless, it probably had a marked effect on the general public. Visions of Dr Frankenstein are easily aroused.
In my opinion, the media stories were mostly hype. I believe we remain a long way from mastering the ability to synthesise life from chemicals in a testtube. The word "synthesise" accurately describes the process envisaged, the net effect of which would be to copy pre-existing life. The term "creation" would be appropriate only if an alien form of life were theoretically envisaged and then synthesised.
The article in Science reported scientists from The Institute for Genomic Research (TIGR) in Maryland - working on a bacterium (Mycoplasma genitalium) with the smallest genetic content of any known biological cell - determined the minimum number of genes essential for the bacterium to live under the particular conditions studied. Human cells have about 100,000 genes - M. genitalium has only 480. The TIGR team discovered that only 265 to 350 of the 480 genes in the bacterium are essential.
An organism's genes contain the genetic information that passes from generation to generation and that largely control the day to day chemical activities of the cells. One unit of genetic information is called a gene. Most activities in the cell are carried out by proteins. The genes exert their influence by specifying what proteins are made by the cell. One gene contains the information that specifies one particular protein.
The chemical nature of the gene is DNA, a long molecule made of two strands wrapped about each other in a double helix. Each strand is a long string of units called nucleotides and there are four kinds of nucleotide, denoted A, G, T, C. The information in the gene resides in the linear sequence of these letters and the code is read in groups of three successive letters (codons).
Protein synthesis in the cell is a complex, but carefully orchestrated, process. Proteins are essentially long strings of units called amino acids, of which there are 20 types. The unique nature of any particular protein, e.g. haemoglobin, is determined by the linear sequence of its amino acids, which is specified by the sequence of codons in that protein's gene.
The first step in protein synthesis is transcription of the information in the gene into another long molecule made of nucleotides called messenger RNA (m-RNA). This step requires an enzyme catalyst called RNA polymerase. The m-RNA then associates itself with a complex structure called a ribosome, made from many special RNA and protein molecules. The ribosome acts as a jig to hold the m-RNA molecule. The amino acids that will make up the new protein are now transported to the ribosome-m-RNA complex, each one carried by another type of RNA molecule called transfer RNA (t-RNA). There is a special t-RNA for each amino acid and each has a sequence of three nucleotides (the anti-codon) that recognises the codon on m-RNA for the amino acid it bears. In this way the sequence of amino acids, as specified by the codon sequence on the m-RNA, are linked together. Several enzymes and other factors are required to make these various steps work.
The nucleotide sequence of the minimum essential set of genes in M. genitalium is known and current technology can synthesise these genes from their constituent nucleotides in the laboratory. It is an enormous leap to go from there to synthesising a living cell, but this is what the founder of TIGR, Dr Craig Venter, claims could now be done, given a billion dollars funding.
Genes on their own do nothing - they can only do their natural job in the environment of a living cell. In order to synthesise life, one would have to synthesise the essential components of a living cell and put them together in the right fashion. Every cell is surrounded by a membrane - you would have to synthesise a membrane from its component parts. This can be done with current technology. In order for the cell to make proteins it needs ribosomes and enzymes. These could also be synthesised in the laboratory, but would be a daunting task. The final step would be to entrap just the right mixture of genes, ribosomes, enzymes and many other components within a sphere of artificial membrane, feed it the nutrients needed by a natural cell and hope that the newly synthesised cell kicked into life.
Optimistic projections regarding our imminent capacity to synthesise life seem to be informed by inappropriate analogies, e.g. between life and an audio-cassette player, with DNA representing the tape instructions and the cell representing the hardware that plays the tape. In an audiocassette player you have a predominantly one-way flow of information from the tape to the hardware to produce the sound - in the living cell the flow of information is continuously twoway. The cell tells the DNA which genes to play and in what sequence, and tailors its instruction to suit the environmental conditions. The cell is a delicately orchestrated whole - cassette player just plays what is on the tape.
Although we know a lot about genes, protein synthesis and other molecular interactions, we remain ignorant of many equally complex molecular interactions in the cell that make life possible. Attempts to synthesise life with our present level of understanding would simply mix good DNA with a mangled cell, resulting in a mashing and grinding of gears preceding a shuddering halt. It should eventually be possible, when we know enough, possibly in another 50 years, to synthesise a copy of a living cell. I will discuss the ethical implications of synthesising life in the next article.
William Reville is a senior lecturer in biochemistry and director of microscopy at UCC.