The artificial genome: between science and ethics

[25th May 2010]

It can’t yet be called artificial life but it is the nearest thing to date. Synthia is the first living organism which has had its genome prepared in the laboratory, then transferred into a DNA-less bacterial cell and which, as such, has taken “command” and has given life to other bacterial colonies all containing the synthetic DNA.

The experiment is undoubtedly fascinating, both for the elegance of the technique used and the end result obtained.

The researchers of the group led by Craig Venter, starting off with four pieces of DNA bacteria, were able to replicate it so as to obtain a sequence of more than a million nucleotide bases (the single rings of the DNA chain known as adenine (A), cytosine (C), guanine (G) and thymine (T) capable of expressing 850 genes.

This assembling came about in yeast, where small fragments became attached, overlapping themselves on the edges and creating groups which grew to finally form the circular chromosome.

It is worth remembering that just two years ago the same research group announced that it had beaten the previous record for assembling DNA when it created a molecule twenty times longer than anything synthesised to that date but only about half that which has been announced in the last few days.

What is more, this time the group has been able to make the DNA take control of the host cell and induce it to produce those proteins which are typical of the species from which part of the genome was extracted and also to stimulate reproduction thereby giving life to a progeny entirely characterised by the artificial DNA.

There’s no doubt that Ventner and his scientists have been able to remain one step ahead of the field thanks to their deep knowledge of genetics, molecular biology and bioinformatics.

Thus, it’s possible, if not probable, that science will be able to reach its ultimate goal: that of creating a living organism containing the minimum number of genes necessary for its manipulation in the production of goods (medicine, biofuels, etc.) and services (the cleaning up of polluted sites, the absorbing of CO2 etc.) for the benefit of mankind.

That the team has been able to acquire an advanced understanding is also shown by the fact that Synthia, in addition to being a living thing with a number of genes almost double the number of those to be found in the original species (485), is also the first organism in whose DNA there is an alphanumeric code associated with its genes and proteins. Using this code, the researchers have set a sort of quiz, which once it has been guessed, allows access to a website, which itself is indicated in the DNA. In the same way, the researchers have “signed” the genome with their own names and have written three philosophical maxims.

The use of the code will allow us to trace with certainty the synthetic nature of DNA and its owners.

The overall fascination of Venter’s project and its seemingly philanthropic aims obviously need to be analysed taking into accounts scientific, ethical and research governance aspects.

The first perplexity, which arises spontaneously, concerns whether or not we are able to understand the level of gene interaction in the new DNA.

We know that DNA as such is not a simple sequence of non codified genes and bases but that its disposition influences the final expression of the genome in the phenotype (positional effect). To date, it is known that the bacterium is able to reproduce but what is not known is whether the team intends to study more specifically the overall expression of the synthetic genome given that we can presume that its overall nucleotide sequence has no equal in existing bacterial groups.

The risk that is posed by the creation of a similar organism relates above all to its use in the field as, for example, its use in clearing up oil spillages, contaminated sites or to absorbing CO2. The new organism, in these scenarios, could come into contact with other bacterial groups and through hybridisation could transfer all or part of its characteristics into a different organism.

By seeking to prevent this risk by using bacterial groups which differ from those found naturally in the release environment, the effect could be the opposite of that intended as the bacterial groups might find no resistance to their expansion, with unforeseeable consequences.

Synthia, whose initial building blocks were taken from a pathogen bacterium for certain animals, closely related to a species which causes urinary infections in Man and even closer to a subspecies responsible for pulmonary infections in cattle, will never be released into the environment, at least not voluntarily.

Notwithstanding this and to avoid any such risk, Synthia has been programmed to make it dependent on the environment of the culture and to deactivate the infective functions for those animals which could host it, even if it is resistant to antibiotics, which would be the only weapon capable of controlling its development.

These preventive techniques, however, merit two different considerations: the first concerns the presumable need to allow for the development of the microorganisms which carry out the environmental clean up, thereby making it difficult to control their diffusion; the second concerns the high reproduction rate of the microorganisms and the risk that environmental pressures favour the selection of mutant groups, with unforeseen and unpredictable consequences. This factor needs also to be analysed in the light of the stability of the synthesis genome. This genome differs from the natural processes of replication which lead to the formation of a continuous chain of nucleotides, in that the synthesis genome is the result of the assembling of smaller pieces which therefore present differing joining points. If, and in what way this aspect is able to favour the outbreak of mutations does not seem to have been considered to date.

Further to these questions which are of a scientific nature and which have yet to be adequately addressed by the material coming out of the Venter Institute, the project also raises plenty of ethical and moral questions.

Venter’s stated dream is to put nature, or at least a part of it, under Man’s control. This is an extremely anthropocentric approach which sees the environment only in relation to what it can offer Man himself.

Moreover, synthetic bacteria belong to that category of research products which could have a double use, both as tools at the service of Mankind or tools which could have an offensive capacity, for instance, for the production of chemical weapons. Whether or not the use of such weapons is by a regular army or by terrorist groups seems quite frankly to be a question which is totally irrelevant to Society as a whole.

Venter should be credited for not having made a secret of his intentions and to have started a debate over various ethical questions which concern his work but which also have wider implications for research concerning artificial life and, above all, its applications which merit wider attention.