This text answers the question, posed by the editor, on the philosophical and  social issues resulting from the synthetic assembly of a modified bacterial genome that was introduced in an existing bacterial species (M.mycoides)and so it was claimed to represent the first ever kind of synthetic life produced by human manipulation

Aranda-Anzaldo, Armando

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SYNTHETIC LIFE, WHAT FOR AND WHAT FUTURE?ARMANDO ARANDA-ANZALDOIn late May 2010, a group of researchers lead by J. Craig Venter reportedthe creation of a bacterial cell controlled by a synthetic genome, implyingthat such a genome had been artificially created in the lab 1. This techno-logical development was widely quoted in the media followed by an aura,not to say noise, of big words and big worries: synthetic life, artificial life,creation of life, man playing god, very much fuelled by Venter himself, ashe seems to be convinced of the awesome philosophical meaning of thiswork 2. The plain facts are that a genome from a well-known bacterium(Mycoplasma mycoides) was synthesized and assembled in pieces and thencleverly introduced into a closely-related host bacterium (Mycoplasmacapricolum) where the transplanted genome directed the production of thecellular components now corresponding to those coded by the M. mycoidesgenome, leading to the propagation of this new variant of M. mycoides thatVenter has unabashedly characterized as a new species worth of his ownname (Mycoplasma mycoides JCVI-syn1.0). Venter’s claim for having createda new species is based on the fact that the synthetic M. mycoides genomehas not exactly the same nucleotide sequence of the natural M. mycoides,as the researchers deliberately introduced “watermarks”, meaning artifi-cial nucleotide sequences altogether meaningless from the functionalpoint of view, as molecular labels for distinguishing the synthetic genomefrom the natural one 3. This was an important control step in order to provethat the resulting newly made bacterial cells carry the synthetic genomeand so do not correspond to natural M. mycoides bacteria that may havecontaminated the bacterial cell cultures formerly populated by M. caprico-lum. Thus, this technological feat is analogous to an imaginary Hondatakeover of the failing Ford factories, during the recent world financialcrisis, in order to produce brand new Honda cars. Indeed, the spatiotem-poral order of molecules and biochemical interactions that result in thecellular organization represented by the host M. capricolum was “kid-napped” by the transplanted synthetic genome that from then on repro-Laboratorio de Biología Molecular, Facultad de Medicina, Universidad Autónoma del Estadode México, Toluca, México. / aaa@uaemex.mxThis text answer the question, posted by the editor, on the philosophical, scientific and socialproblems followed from the synthetic ensemble of the modified genome of the bacteria M.Mycoides, announced in May 2010 by the J. Craig Venter Institute.Ludus Vitalis, vol. XIX, num. 36, 2011, pp. 213-215.duced such a preexisting cellular organization but using M. mycoidescomponents. In no way the synthetic genome was able to determine thepreexisting cellular organization and so the old dictum attributed toPasteur Omne vivum ex vivo (all life arises from preexisting life) remains asvalid and mysterious as ever, despite Venter’s claims on the contrary. Interestingly, Venter says that the synthetic assembly of a workingbacterial genome is a major step in an ongoing fifteen year-old researchproject whose central aim is achieving the creation of a living cell with aminimal working genome 1. Apparently, a major question for Venter andassociates is which genes are essential and which genes are dispensablefor cellular life. For example, a single base pair deletion that creates aframeshift in dnaA, a gene that codes for an enzyme essential for chromo-some replication, was enough to preclude the successful transplantationof the synthetic genome. On the other hand, unexpected accidental inser-tions of transposons occurring during the procedure for assembling thesynthetic genome, resulted in the disruption of two genes whose inacti-vation did not preclude the successful transplant of the synthetic genomethat was able to replicate in the new host 3. Hence, Venter qualifies dnaAas an essential gene while the disrupted genes are non-essential. One wonders about this obsession with simplifying a genome that isthe natural result of evolution. Indeed, classifying genes as essential ornon-essential is a risky business. It all depends on the arbitrary criteriachosen for such an evaluation. For example, in the case of metazoans theremay be genes whose mutation is non-compatible with embryonic devel-opment (embryonic lethal genes) and so development is early aborted.Yet, other genes that cause no harm to the embryo when mutated and soare apparently non-essential for development, may nevertheless cause thesterility of the adult animal then unable to reproduce. In both cases, thereis a breakdown in the ability to pass a given genotype to an offspring.Moreover, there is overwhelming evidence that redundancy at both thegenetic and functional levels is a fundamental condition of life 4. Such aredundancy is a critical feature that guarantees the resilience and adapt-ability of living things in an always shifting environment. Living thingsare not built like cars in a factory where quality control checks are appliedto newly-made lots of parts and pieces before being used for the assemblyof new cars, which are also selectively subjected to further quality-controlchecks before going into the market. In this case, an economy of savingsin operational costs and avoidance of costly consumer’s lawsuits deter-mines the industrial practices. However, nature is rather wasteful whenbuilding things and the quality control is carried ex post by natural selec-tion 5. The goal of creating synthetic cells or organisms based on minimalworking genomes may be appealing from a financial perspective, aimingat maximum revenues from minimal investment, yet it carries the seed of214 / LUDUS VITALIS / vol. XIX / num. 36 / 2011disaster as the loss of redundancy within the system increases its frailtyand potential for critical malfunction. Indeed, highly important and ex-pensive man-made devices have significant built-in redundancy: spaceshuttles, nuclear submarines, nuclear-power plants, jet airliners, and soforth, in order to reduce the risk of critical failure.In any case, more than wasting our time with the exegesis of Venter’sachievements it is worth considering the rationale behind the syntheticbiology fad. At the end of the day, all these efforts are justified with theclassical argument for the benefit of mankind: new bacteria that will eatand degrade the oil from spills, vegetables that will produce useful drugsin their saps, cells that will secrete the right products for making the rightvaccines against dreadful diseases, and so forth 1. That sounds nice andmarvelous. Yet one wonders. When there are no oil spills to tame whathappens to the oil-eating bacteria, will they remain safely latent, frozen intheir liquid nitrogen casks? And if by some mistake they happen to fellinto the oil-storage tanks of a major oil refinery? That would be theultimate feast for such synthetic organisms! Then, shall we need massiveamounts of antibiotics (perhaps produced by another synthetic organism)in order to kill the oil-eating bacteria menacing to wreak havoc on the oilindustry? Moreover, once the former useful drug for controlling gas-troesophageal reflux is replaced by a better drug, what would happen tothe synthetic vegetables that produced the former drug in their sap? Willsuch plants go into nostalgic display in botanical gardens? Will theyundergo the same fate as 33 rpm acetate records, Betamax videos, cassettetape-recorders, typewriters, floppy disks? What would happen to all theseman-modified or man-created life forms once their useful purpose hasbeen fulfilled and superseded by new human needs, trends and fashions?Then I am afraid, we will begin to worry about what to do with thatinvasion of useless, out of fashion, synthetic life-forms in the same waythat today we have piles of discarded TV sets, old computers, used batteriesand nuclear waste posing a serious problem of containment and disposal.NOTES1 See video at http://www.ted.com: “Craig Venter unveils synthetic life” (You-Tube)2 Cho, M.K. and Relman, D. A. (2010), “Synthetic “life”, ethics, national security,and public discourse,” Science 329: 38-39.3 Gibson, D. G., et al. (2010), “Creation of a bacterial cell controlled by a chemi-cally synthesized genome,” Science 329: 52-56.4 Aranda-Anzaldo, A. and Dent, M. A. R. (2003), “Developmental noise, ageingand cancer,” Mech. Ageing Dev. 124: 711-720.5 Aranda-Anzaldo, A. and Dent, M. A. R. (2007), “Reassesing the role of p53 incancer and ageing from an evolutionary perspective,” Mech. Ageing Dev. 128:293-302.ARANDA-ANZALDO / WHAT FOR? / 215

Synthetic life, what for and what future?

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Synthetic life, what for and what future?

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