First life, and next life: The origins and synthesis of living cells

In 1944, the physicist and Nobelist Erwin Schrödinger published a book with the title What is Life? Schrödinger stated on the first page of his book that he would address a fundamental question: "How can the events in space and time which take place within the spatial boundary of a living organism be accounted for by physics and chemistry?” That remains an open question more than sixty years later, but we have learned so much more about the history of life on the Earth that we can ask a related question: “What was life?” Because several research groups are attempting to fabricate synthetic life in the laboratory, we can also ask a question in future tense: “What will life be?” As scientists addressed these questions over the past decade, a remarkable connection began to emerge between our understanding of life on the Earth and the stellar processes that give rise to solar systems with habitable planets. In order to support research on this connection, NASA initiated a new scientific program called astrobiology. One of the goals of astrobiology is to discover how life originated on our planet and whether it exists beyond the Earth. To get some idea of the scope of this question, consider for a moment what a planetary surface in our solar system was like four billion years ago, before life began. The surfaces of the Earth and Mars were hot, mostly covered by salty oceans containing a dilute solution of thousands of organic compounds. Volcanic land masses emerged from boiling seas, and tidal wet-dry cycles occurred daily where sea met land. Water continuously evaporated from the interface between sea and atmosphere, condensed as rain and fell on the volcanic islands where it formed small pools containing organic solutes. From this unpromising chaos of land, sea and atmosphere, the first life somehow emerged, certainly on the Earth, perhaps on Mars.

My research associates and I have been studying self-assembly processes in natural geothermal environments and related laboratory simulations that simulate what the Earth was like before life began. We can be reasonably confident that liquid water was required, together with a source of organic compounds and energy to drive polymerization reactions. The clue that we are following is that certain molecules have properties that allow them to assemble into more complex structures, a familiar example being the way that soap molecules can self-assemble into the spherical structures we call soap bubbles. In earlier work we observed that macromolecules such as nucleic acids and proteins are readily encapsulated in membranous boundaries during wet-dry cycles such as those that would occur at the edges of geothermal springs or tide pools. The resulting structures are referred to as protocells, in that they exhibit certain properties of living cells and are models of the kinds of encapsulated macromolecular systems that would have led toward the first forms of cellular life. At some point it seems likely that we will know enough to try to fabricate living molecular systems in the laboratory, and from this effort learn more about the hurdles that the first forms of life must have overcome. For instance, simple protocells have been produced by encapsulating enzymes and nucleic acids in cell-sized lipid vesicles. RNA and DNA have been enzymatically synthesized in such microenvironments, and encapsulated ribosomes can translate genes embedded in messenger RNA into specific proteins. The most complex protocell model system incorporates a synthetic DNA molecule with several genes. The genes are enzymatically transcribed to messenger RNA, then expressed as proteins by ribosomes. This achievement is astonishing, but there is still far to go before a living cell can be assembled from a parts list. The reason is that well over a hundred genes must be expressed even in the simplest version of a complete artificial cell, half of these simply to assemble ribosomes. In my talk I will outline several approaches to synthetic life, and describe how we can learn about the origin of life by to reassemble cells in the laboratory.

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