GRAND CHALLENGE 1.
SYNTHESIZING LIFELIKE SYSTEMS

Living systems provide proof-of-concept for what can be achieved physically. Can the combined skills and knowledge sets of biological and physical scientists provide greater insight into identifying those structures, capabilities, and processes that form the basis for living systems and then, with that insight, construct systems with some of the characteristics of life that are capable, for example, of synthesizing materials or carrying out functions as yet unseen in natural biology?

For centuries, humans have analyzed the properties of living organisms and built structures to mimic their functions. While most efforts have been at somewhat rudimentary levels, advances in the physical and life sciences now provide us with the technical and scientific sophistication to pursue almost limitless possibilities in this arena. Concepts such as emergent properties, familiar to condensed matter theorists, are helping to describe how biologically complex systems arise from prebiotic chemistry and geochemistry. Other ideas from the physical sciences, such as dynamical systems theory, energy landscapes, and multistability, are helping to explain fundamental issues such as how organisms behave in response to their environments and how information is used to sustain life.1 Using the knowledge gained in these and other studies, we face the ambitious possibility of generating synthetic units with basic attributes of living matter such as compartmentalization, metabolism, homeostasis, replication, and the capacity for Darwinian evolution. Such self-replicating, evolving organisms have the potential to create more efficient functions for a broad range of applications. At the same time, pursuing this challenge will provide us the opportunity to explore and expand our understanding of the principles of self-replication and evolution.

Any such efforts will require the duplication of essential components of living systems. For example, Darwinian evolution requires a molecular basis for heritable variation, suggesting that any such system must contain a polymer like RNA or DNA with the ability to store and encode information in a simple way. This genetic material must be able to replicate, which requires either a simple autocatalytic system or chemistry that enables spontaneous replication. The scientific community has made some progress toward these goals by, for example, chemically synthesizing natural genomes and then replacing the original genomes in living cells with these synthesized genomes and, in a more bottom-up approach, developing and studying “protocells” as a demonstration of how simple nucleic acids self-replicate within a lipid envelope.

In addition, the products of replication must be held in proximity for some

1

Many of these topics are touched on in more detail in Chapter 4. Also, see National Research Council, The Role of Theory in Advancing 21st Century Biology, Washington, D.C.: The National Academies Press, 2008, for related discussions.



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