Sizing up the 'synthetic cell'
asked eight experts about the implications of the J. Craig Venter Institute's latest creation.
A synthesized genome has been assembled, modified and implanted into a DNA-free bacterial shell to make a self-replicating Mycoplasma mycoides bacterium1. Here, Nature presents short extracts from eight comment pieces on what this achievement means for biotechnology, evolutionary biology, regulation and philosophy. The full-length comments are available to read here.
"The ability to make prosthetic genomes marks a significant advance over traditional genetic engineering of individual genes. It raises important scientific and societal issues: we now have an unprecedented opportunity to learn about life. We must develop and perfect new methods for engineering emergence, as this calls for fundamental innovations in precautionary thinking and risk analysis. It will revitalize perennial questions about the significance of life — what it is, why it is important, and what role humans should have in its future."
"With regard to regulations to prevent the release of hazardous life forms made in ways akin to the new Mycoplasma or by other means, there are two scenarios: bioerror and bioterror. For the former, licensing and surveillance, handled by computers, minimally inconvenience researchers, while sensitively detecting deviations from normal practice and smoothly integrating new risk scenarios. For bioterror avoidance, realistic lab ecosystems should be standardized to test the ability of new synthetic genomes to persist or exchange genes in the wild."
"Now that the JCVI has demonstrated how to reassemble a microbial genome, it may be possible to answer one of the great remaining questions of biology: how did life begin? Using the tools of synthetic biology, perhaps DNA and proteins can be discarded — RNA itself can act both as a genetic molecule and as a catalyst. If a synthetic RNA can be designed to catalyse its own reproduction within an artificial membrane, we really will have created life in the laboratory, perhaps resembling the first forms of life on Earth nearly four billion years ago."
"Venter and his colleagues have shown that the material world can be manipulated to produce what we recognize as life. In doing so they bring to an end a debate about the nature of life that has lasted thousands of years. Their achievement undermines a fundamental belief about the nature of life that is likely to prove as momentous to our view of ourselves and our place in the Universe as the discoveries of Galileo, Copernicus, Darwin and Einstein."
"Implementing a synthetic genome in a modern cell is a significant milestone in understanding life today. However, the radical 'top-down' genetic engineering that Venter's team has done, does not quite constitute a "synthetic cell" by my definition. 'Bottom-up' researchers, like myself, aim to assemble life — including the hardware and the program — as simply as possible, even if the result is different from what we think of as life. Constructing life using different materials and blueprints will teach us more about the nature of life than will reproducing life as we know it."
"This is an important advance in our ability to re-engineer organisms, not make new life from scratch. Frankly, scientists don't know enough about biology to create life. Although the Human Genome Project has expanded the parts list for cells, there is no instruction manual for putting them together to produce a living cell. It is like trying to assemble an operational jumbo jet from its parts list — impossible. Although some of us in synthetic biology have delusions of grandeur, our goals are much more modest."
"The JCVI work may help to link chemistry to natural history. The sequences of the genomes of extinct ancestral Mycoplasma species might be inferred from the sequences of various modern mycoplasmae, including M. capricolum, M. genitalium and M. mycoides — the three bacteria that Venter and his colleagues' synthesis started with. The new synthetic technology allows resurrection of such ancient bacteria, whose behaviour should inform us about planetary and ecological environments 100 million years ago."
"It is a technical advance, not a conceptual one. Chimeric organisms have long been created through breeding and, more recently, through the transfer of native genomes into denucleated target cells. Chimeric organisms with synthetic genomes contain engineered but natural genetic components. They are subject to evolution, a natural law that cannot be tricked. Whether these organisms will face natural limits, such as impaired reproduction or a shortened lifespan, remains to be seen."
- Gibson, D.A. et al., Science advance online publication doi:10.1126/science.1190719 (2010)