INSIGHTS | P E R S P E C T I V E S

enzymatic activity, to block caspase-1 activa-

tion in the presence of microbial products
(8). This suggests the existence of multiple
layers of regulation for these inflammatory
caspases during infection.
In contrast to oxPAPC binding, the func-
tion of the caspase-11 catalytic domain is
required for cleavage of Gsdmd, which is
potentially the executioner protein in cas-
pase-11– and caspase-1–dependent cell death.
Zanoni et al. show that there is no cell death
correlated with activation of caspase-11;
thus, perhaps oxPAPC binding to the cas-
pase-11 catalytic domain blocks cell death by
inhibiting Gsdmd cleavage in dendritic cells.
Future studies should reveal the physiologi-
cal importance of oxPAPC and Gsdmd, and
their interactions, in caspase-11 activation

Downloaded from http://science.sciencemag.org/ on October 14, 2016

and cell death. ORIGIN OF LIFE
Zanoni et al. uncover a role for host lip-
ids in controlling caspase-11 activation and
cell death. Such knowledge is important for
understanding the involvement of caspase-11
Beyond prebiotic chemistry
in disease models where LPS is scarce. For What dynamic network properties allow the emergence of life?
example, caspase-11–dependent cell death
plays an important role in neuronal necro-
sis in models of stroke, multiple sclerosis, By Leroy Cronin1 and Sara Imari Walker2,3 research efforts have focused on detailing
Parkinson’s disease, and methamphetamine- precise chemical mechanisms for producing

H
induced inflammation (9–12). Additionally, ow can matter transition from the high yields of individual bio-inspired prod-
it is currently unknown whether caspase-11 nonliving to the living state? The an- ucts, without addressing the processes neces-
plays a role during viral infection. Thus, swer is essential for understanding sary to form increasingly complex molecules
studies to identify the role of endogenous li- the origin of life on Earth and for and networks.
gands, such as oxPAPC, and their regulation identifying promising targets in the What happens to our traditional perspec-
of caspase-11–induced inflammation during search for life on other planets. Most tives if we do not restrict attention to the
neuronal injury and viral infection will be of studies have focused on the likely chemistry chemical substrates of known life? The de-
great importance. of RNA (1), protein (2), lipid, or metabolic velopment of networks over time may be
Many gaps remain in our knowledge of “worlds” (3) and autocatalytic sets (4), includ- more important than the specific chemical
caspase-11—specifically, how activation and ing attempts to make life in the lab. But these nature of their molecular components: Even
its resolution are regulated, and how this efforts may be too narrowly focused on the RNA can form cooperative networks, diver-
regulation differs by cell type and can affect biochemistry of life as we know it today. A sifying its potential role in the earliest evolv-
the adaptive immune response. Zanoni et al. radical rethink is necessary, one that explores ing chemistries (5); autocatalytic networks
reveal previously unsuspected functions of not just plausible chemical scenarios but also can evolve in the absence of genes (4). The
host lipids in regulating caspase-11 activa- new physical processes and driving forces. first networks would have had to be simple,
tion and cell death. In addition, their find- Such investigations could lead to a physical challenging the notion that highly complex
ings demonstrate how the innate immune understanding not only of the origin of life and improbable molecules are needed to
system has evolved to decode the complex- but also of life itself, as well as to new tools jump-start life. The molecular constituents of
ity of microbial- and host-derived signals to for designing artificial biology. simple networks are more likely to arise by
harness an appropriate adaptive immune A transition from the limited function and chance than the highly evolved molecules of
response to infection. j memory possible in a soup of weakly inter- extant life. Starting from networks composed
REFERENCES AND NOTES acting molecules to more strongly interacting of simple molecules could therefore dra-
1. I. Zanoni et al., Science 352, 1232 (2016). networks was essential for the emergence of matically reduce the time necessary for the
2. J. Shi et al., Nature 514, 187 (2014). life on Earth (see the figure). Left unattended, emergence of life and potentially increase the
3. N. Kayagaki et al., Nature 479, 117 (2011).
4. N. Kayagaki et al., Nature 526, 666 (2015). sophisticated chemistry becomes more dilute probability of an origins event.
5. Y. Shirasaki et al., Sci. Rep. 4, 4736 (2014). and disordered. A quick route to complex- A concept of information relevant to
6. T. Liu et al., Cell Rep. 8, 974 (2014). ity and enrichment that could lead to the biological organization may be essential to
7. F. Py et al., Cell Rep. 6, 1122 (2014).
IMAGE: WALTER MYERS/SCIENCE SOURCE

8. M. Saleh et al., Nature 440, 1064 (2006). development of evolvable units seems to be identifying these networked processes. Ad-
9. S. J. Kang et al., J. Cell Biol. 149, 613 (2000). required to avoid this serious issue. Yet, most ami and LaBar have described life at a basic
10. S. Hisahara et al., J. Exp. Med. 193, 111 (2001).
11. T. Furuya et al., J. Neurosci. 24, 1865 (2004). level as “information that copies itself” (6).
12. W. Huang et al., Toxicol. Sci. 145, 68 (2015). Given that life not only copies information
1
WestCHEM, School of Chemistry, University of Glasgow, but also uses information to construct itself,
ACKNOWLEDGMENTS
Funding from the National Institute of Allergy and Infectious
Glasgow G12 8QQ, UK. 2School of Earth and Space Exploration, we might instead describe the start of life as
Beyond Center for Fundamental Concepts in Science, “simple machines that can construct slightly
Diseases, National Institutes of Health Award AI095396-05
Arizona State University, Tempe, AZ 85287, USA. 3Blue Marble
(D.M.M.) and 1F32AI115950-01 (B.A.N.). more complicated machines.” Focusing on
Space Institute for Science, Seattle, WA 98154, USA.
10.1126/science.aag0366 Email: [email protected]; [email protected] information in this way moves the narrative

1174 3 JUNE 2016 • VOL 352 ISSUE 6290 sciencemag.org SCIENCE

Published by AAAS
 Artist’s impression of the young Earth. Life evolved namical systems, including the origins of will be understood within a single unified
shortly after Earth’s surface cooled enough for a solid social systems (11). Such comparisons could theory or will be shown to involve different
crust to form. yield insights into universal properties of processes (12, 13). In connecting these ar-
dynamic networks. eas, understanding common features such
even further from a chemistry-specific mode However, speculation should be restricted as the emergence of complexity becomes
than focusing on networks alone but may to the development of experimentally test- important. For example, how complex must
perhaps provide our best shot at uncover- able hypotheses that address key questions a chemical signature need to be before it
ing universal laws of life that work not just and provide a focus for progress. First, how can be considered a biosignature? Look-
for biological systems with known chemis- did evolution begin if the complex machinery ing for complex objects that could not form
try but also for putative artificial and alien for evolution was not in place? Experimen- randomly in an environment, but arise only
life. For example, Walker et al. have recently tal studies addressing this question could as a result of lifelike machinery, might help
shown that information-theoretic measures evaluate the evolvability and robustness of in classifying potential biosignatures and
distinguish biological networks from ran- molecular networks or systems with a lower the processes that generate them. Earth’s
dom ones, even in cases where the biological molecular complexity than a full-blown ribo- complex inorganic and organic worlds are
networks share important network proper- some. Second, can the emergence of life be certainly highly connected in this respect,
ties (such as topological features) with ran- substrate-independent? Answers may come with even Earth’s mineral diversity in part
dom networks (7). Life requires chemistry, from investigation of evolvable chemical dictated by life (14).
but the properties of the living state emerge Progress will be made by challenging all

Downloaded from http://science.sciencemag.org/ on October 14, 2016

from the dynamical properties of that chem- historical prerequisites assumed to be impor-
istry, including the temporal and spatial or- tant in the origin of life. We should aim to
ganization of molecular networks and their “Focusing on information… develop measurable and collaborative routes
information management.
Another way to reconceptualize the prob-
may perhaps provide our best to explore the physics and chemistry of life’s
origins and the living state. Not only is a com-
lem is to consider life’s emergence as a shot at uncovering universal prehensive understanding of what it means
phase transition that manifests as a sudden
change in how chemistry can process and
laws of life that work not just for a physical system to be alive required but
also a new multidisciplinary, multinational
use information and free energy. Under- for biological systems with project to generate new life in the lab or in
standing this phase transition requires new silico, to search for life on Earth that uses an
approaches to nonequilibrium physics that
known chemistry but also alternative chemistry to that found in biol-
hold promise for explaining the origin of for putative artificial and ogy (15), and to explore the potential for life
structure at multiple hierarchical scales (8). on other worlds. For this to be possible, re-
Heterogeneity in the early Earth environ-
alien life.” searchers must challenge the current models
ment played a central role in facilitating the and historical approach and be willing to
emergence of life by helping to sustain, se- pathways in the laboratory that are based work together across disciplinary boundaries
lect, and drive the emergence of organized on alternative polymers. This includes dem- to see if a process-based model can be used to
systems that could persist over time. For ex- onstrating how function can be transferred understand and control the transition from
ample, pores in rocks may have influenced between molecules with different chemical inorganic matter to biology. j
chemical selection, leading to increasingly make-up while preserving the overall net-
RE FERENCES AND NOTES
lifelike chemistries over time (9). work structure. Third, at what point in the
1. S. A. Benner, H. J. Kim, M. A. Carrigan, Acc. Chem. Res. 45,
One important order parameter in char- historical origins of life did the current chem- 2025 (2012).
acterizing life’s origin as a phase transition istry of life get selected? Could more than one 2. M. Rodriguez-Garcia et al., Nat. Commun. 6, 8385 (2015).
is the homochirality. Jafarpour et al. have version of biology exist on the planet today or 3. J. C. Blain, J. W. Szostak, Ann. Rev. Biochem.83, 615 (2014).
4. V. Vasas, C. Fernando, M. Santos, S. A. Kauffman, E.
shown that homochirality emerges spon- in the past? This could in principle be tested Szathmáry, Biology Direct 7, 1 (2012).
taneously as a symmetry-breaking process in one-pot experiments and simulations that 5. N. Vaidya et al. Nature 491, 72 (2012).
in models of noisy autocatalytic systems, a include in vitro competition between alterna- 6. C. Adami, T. LaBar, From entropy to information: Biased
typewriters and the origin of life, http://arxiv.org/
result that could be experimentally tested tive chemical scenarios for early life. abs/1506.06988 (2015).
(10). Insights may also come from studying In more abstract terms, it remains unclear 7. S. I. Walker, H. Kim, P. C. W. Davies, Philos. Trans. R. Soc. A
other transitions in the biosphere where whether the problems of life’s origin, evo- 374, 20150057 (2016).
8. H. Morowitz, E. Smith, Complexity 13, 51 (2007).
organization has emerged from messy dy- lution, and understanding the living state 9. W. Martin, M. J. Russell, Philos. Trans. R. Soc. Lond. B Biol.
Sci. 358, 59 (2003).
10. F. Jafarpour,T. Biancalani, N. Goldenfeld, Phys. Rev. Lett.
115, 158101 (2015).
11. S. DeDeo, Major transitions in political order, http://arxiv.
org/abs/1512.03419 (2015).
Nonliving network Living network 12. D. H. Erwin, Curr. Biol. 25, R930 (2015).
Radical chain reaction DNA polymerase 13. E. Bapteste, Trends Genet. 29, 439 (2013).
• •+ chain reaction 14. E. G. Grosch, R. M. Hazen, Astrobiology 15, 922 (2015);
ILLUSTRATION: V. ALTOUNIAN/SCIENCE

10.1089/ast.2015.1302.
• + • Replication Information Error Evolution 15. P. C. W. Davies, Philos. Trans. R.Soc.A 369, 624 (2011).
propagation correction
ACKNOWL EDGMENTS
This Perspective was inspired in part by a workshop held at
the Carnegie Institution for Science in Washington, D.C., from
9 to 15 November 2015, and we thank the contributors to this
Comparison of nonliving and living networks. Nonliving and living systems both replicate or copy, but the DNA- conference.
based living network allows information propagation, evolution, and error correction. Progress in understanding the
origin of life may come from studying how simple chemical networks can transform into living networks. 10.1126/science.aaf6310

SCIENCE sciencemag.org 3 JUNE 2016 • VOL 352 ISSUE 6290 1175

Published by AAAS
 Beyond prebiotic chemistry
Leroy Cronin and Sara Imari Walker (June 2, 2016)
Science 352 (6290), 1174-1175. [doi: 10.1126/science.aaf6310]

Editor's Summary

Downloaded from http://science.sciencemag.org/ on October 14, 2016

This copy is for your personal, non-commercial use only.

Article Tools Visit the online version of this article to access the personalization and
article tools:
http://science.sciencemag.org/content/352/6290/1174

Permissions Obtain information about reproducing this article:

http://www.sciencemag.org/about/permissions.dtl

Science (print ISSN 0036-8075; online ISSN 1095-9203) is published weekly, except the last week
in December, by the American Association for the Advancement of Science, 1200 New York
Avenue NW, Washington, DC 20005. Copyright 2016 by the American Association for the
Advancement of Science; all rights reserved. The title Science is a registered trademark of AAAS.