Slippery Cellularities

Analysis / by James King /

Synthetic biology can mean reconstructing organisms, redesigning biology, or recreating life—and each of these uses has different implications.

Courtesy of James King

The J. Craig Venter Institute has successfully synthesized an entire bacterial genome and transplanted it into a different bacterial cell. That cell then reproduced, replicating the synthetic genome in all its progeny. Mycoplasma mycoides JCVI-syn1.0, or “Synthia” as it has become known, is an enormous technical achievement and brings the first chapter of synthetic biology to a close—a chapter in which the tools of genomic synthesis have been developed and proven. But as Venter himself has pointed out, this is not life from scratch. Other than inserting some genomic “watermarks” to sign their creation, Venter’s team closely followed nature’s pre-existing blueprints in designing their genome. The real act of creation is yet to come.

“Synthetic biology” is a catch-all label liberally applied to a host of methods for designing and constructing living things. Given the term’s multiple definitions, one of Synthia’s most immediately useful applications may be to place the achievement it represents within the context of synthetic biology’s various flavors, in order to clarify what the creation of artificial life might actually mean.

Reconstructing an organism

Synthia is a reconstruction of a living thing. Venter and his colleagues wanted to demonstrate that it is possible to synthesize an entire genome indistinguishable in function and identical in every way to its natural counterpart (except for the additional watermarks). By increasing the power and widening the scope of synthesis to encompass an entire genome, Venter and his team may well have enabled a whole host of future discoveries. However, because Synthia is a copy of an existing bacterium, it gives us little clue as to the actual potential for designing organisms in the future. Synthia is primarily a proof of concept. The next challenge is to design every aspect of an organism’s genome by mixing and matching any genes found in nature.

Redesigning biology

But man-made biology has the potential to operate in a very different way than natural biology. The work of Jason Chin at the MRC Laboratory of Molecular Biology in Cambridge provides a good example of what might be possible. Chin and co-workers have successfully created a synthetic modified ribosome that reads the nucleotides of RNA, not in triplets like the natural ribosome, but in quadruplets. By doing so, Chin has effectively created a new and expanded genetic code that could enable the design of novel proteins incorporating up to 200 different amino acids rather than the 20 found in natural protein synthesis. Chin’s work isn’t so much about designing with biology, but redesigning biology itself, and is just one example from a host of teams pursuing similar research.

Recreating life

Beyond the reconstruction and redesign of life, the most ambitious goal of synthetic biology is arguably the actual recreation of life—“abiogenesis,” the generation of living things from purely nonliving material. A group of synthetic biologists from the UK led by Cameron Alexander, Lee Cronin, Ben Davis and Natalio Krasnogor are attempting to create truly artificial life from completely novel non-biological chemistries that mimic the behavior of natural cells. They call these constructions chemical cells or “Chells.” The Chell project is in its early stages and is an example of “bottom-up” synthetic biology, which is a much more speculative approach than Venter’s targeted “top-down” attempt to construct a particular organism. Bottom-up synthetic biologists are not attempting to tweak or reproduce a preexisting organism, so much as they are trying to create an entirely new type of life and understand life’s origins. If synthetic biologists were mechanical engineers, the top-down group would be modifying and reverse-engineering existing machines to create new ones; the bottom-up teams would be making their machines—and all their parts—from scratch.

As a designer, I have been working with the Chell team to explore the potential implications of creating life. If such a thing is possible, we must explore how our understanding of living things would be altered.

To do this, I imagined what a successful attempt at creating life would be like. Just as Synthia took 15 years of painstaking research, any attempt to build a new biology from basic chemical components will require many years of trial and error. After all, that process appears to have taken many, many millions of years in nature. Therefore, I developed a scenario in which a new type of life is pieced together bit by bit. Rather than focus on the end result, the scenario shows the intermediary steps along the way.

As this is a fictional scenario, it is not based on the science behind the Chell project. Instead, the story has been transposed to a medical context in which chemical cells have been developed as a pharmaceutical technology.

Cellularity from James King on Vimeo.

The central idea behind this scenario is that we might one day understand life, not as a hard-edged category, but as a graduated scale between nonliving and living things. Each developmental stage in chemical cell biology is slightly more alive than the stage before. To formalize this idea, I designed a speculative definition of life named the “Cellularity Scale” which shows how five different living properties accumulate at each subsequent stage. Of course, this is a purely speculative definition of life, consistent with the scenario I have designed. If the Chell project or any of the several other bottom-up attempts at abiogenesis are successful, they will quite possibly offer an entirely different picture.

Whether reconstructing, redesigning, or recreating, the credo of synthetic biology can perhaps best be summarized with a sentence from the ever-quotable late physicist Richard Feynman: “What I cannot build, I cannot understand.” Indeed, this quote is now encoded as a watermark into Synthia’s genome. It’s an apt description of a field in which researchers quite literally design the objects of their study. One way or another, our understanding of life itself will be changed by the things we make.

Originally published June 21, 2010

Tags biology biotechnology genetics public perception scale

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