Laboratory equipment in the MICALIS quantitative metagenomics (MetaQuant) experimental facility. © INRA, INRA

How synthetic biology could benefit from the social sciences

How synthetic biology views life’s complexity

Different researchers have different perspectives on life’s complexity; synthetic biologists see it as a lock to be picked open.

By Pascale Mollier, February 2012 OPECST report, translated by Jessica Pearce
Updated on 12/08/2014
Published on 10/10/2014

Automated pipetting system in the MegaGenoPolis and MICALIS high-thoroughput sequencing experimental facility. © INRA, NICOLAS Bertrand
Automated pipetting system in the MegaGenoPolis and MICALIS high-thoroughput sequencing experimental facility © INRA, NICOLAS Bertrand

The complexity of human cellular dynamics can be described in a few figures. Each human cell contains around 23,000 genes, and each gene can produce up to six transcripts; gene expression varies depending on cell function. The human body contains 60 trillion cells, and hundreds of thousands of interactions take place within each (1).

Emergent properties and orthogonality

Emergent properties are one facet of life’s complexity. For example, an emergent property is a novel and unexpected feature that results as you move from one scale to the next (e.g., from molecules to cells). The existence of emergent properties means that it is difficult to anticipate the consequences of manipulating a complex system.

The concept of emergent properties contrasts with that of orthogonality, a notion commonly exploited in computer science. Orthogonality is the idea that a system’s properties will remain unchanged if even one of the system’s components is modified. For example, adjusting the rearview mirror of a car does not affect how the car runs. Applying orthogonality to living systems means viewing them, at least initially or in part, as an assemblage of separate, autonomous subsystems. According to some biologists, this perspective contrasts with the prevailing view in the “omics” sciences (e.g., genomics, transcriptomics, proteomics, and metabolomics) that living systems consist of a complex set of interactions.

Synthetic biology, by embracing orthogonality, differentiates itself from the “omics” and thus affirms its unique scientific identity.

“I hate emergent properties”

Drew Endy, one of the field’s leaders and an engineer, has certainly been among the most vociferous in criticizing the idea that life’s complexity is a factor that limits the progress and relevance of synthetic biology research. In 2008, he stated in an interview, “I hate emergent properties. I like simplicity. I don't want the plane I take tomorrow to have some emergent property while it's flying” (2).In 2011 (3), he wrote:“…what we’re starting with is this naive idea that we could implement an abstraction hierarchy (4) for managing biological complexity. Where somebody could be an assistant engineer, let's say they want to reprogram the odor of E. coli (5), and they wouldn’t need to know that DNA is made up of 4, or 6, or 8 bases, let alone anything about how to synthesize it.”Researchers using this approach are becoming more and more interested in control and regulatory processes, particularly those involving RNA, and are focused on limiting the influence of emergent biological processes. The most-cited articles in this field are authored by researchers working in institutions founded or currently led by Drew Endy, whose motto amounts to “let’s make biology easier to engineer.”

Biological complexity: a real challenge for researchers but not an impediment

The National Research Council (6) has underscored the importance of acquiring new knowledge. It has pointed out that at least 25% of the genes identified in bacterial genomes are hypothetical in nature or have unknown functions. In a 2010 report entitled “Sequence-based Classification of Select Agents,” the council said: “The  scientific  community  does  not  have  sufficient  knowledge  to create a  novel,  viable  life  form,  even  a  virus,  from  the  bottom  up.” Another recent article (7) has analyzed the current challenges that should be anticipated when it comes to creating functional synthetic organisms. Furthermore, the INRA CIRAD Common Advisory Committee for Ethics in Agricultural Research, in the previously cited 2014 report, recommends that scientists “avoid arrogant perspectives that suggest that living systems can be parsed apart and rendered predictable by making an abstraction of the evolutionary context that originally shaped them.” The committee nonetheless highlights certain new approaches that use engineering techniques in tandem with artificial selection, by subjecting organisms that carry synthetic genomes to environmental selection (as in 8): “certain synthetic biology research teams are already developing high throughput-type tools that, when combined with the efficient generation of mutations and application of selection pressures—can speed and amplify the production of organisms bearing synthetic genomes that are highly adapted to specific environments.”

Consequently, whether in the field of molecular biology or synthetic biology, life’s complexity has not discouraged researchers seeking general knowledge, even if it has been impossible, as of yet, to synthesize an entire organism. In building simple genetic circuits, synthetic biologists have made advances in programming cell behavior and have a better understanding of the rules that frame how natural networks function.

(1) Presentation given by Marie Montus (Genethon Institute, Évry) on September 18, 2007, during a French-language conference on how integrative biology can inform the health sciences (“Colloque sur la biologie intégrative : une nouvelle lecture des pathologies”; part of theTransversales Santé series)
(2) 2008 interview with the Edge Foundation (www.edge.org; The Third Culture series)
(3) Endy, D. (2011). Building a New Biology. Comptes Rendus de Chimie, 14(4), 424-428.
(4) This conceptual scheme considers that complex non biological systems are composed of orthogonal subsystems.
(5) Earlier in the interview, Drew Endy mentions experiments in which the insertion of DNA sequences into E. coli bacteria cause the production of banana or wintergreen scents.
(6) The National Research Council is the operating arm of the US National Academy of Sciences and National Academy of Engineering; its mission is to inform government policy and educate the public about scientific matters.
(7) Cardinale, S. and Arkin, A. P. (2012). Contextualizing context for synthetic biology - identifying causes of failure of synthetic biological systems. Biotechnology Journal,7(7),856-66. DOI:10.1002/biot.201200085.
(8) Ferry, M. S., Hasty, J. and Cookson, N. A. (2012). Synthetic biology approaches to biofuel production. Biofuels, 3(1),9-12. BioCircuits Institute, University of California, San Diego, CA, United States.

The definition of life

Can artificial life still be considered to be life? Are we taking the risk of being invaded by artificial organisms that appear to be alive but that are not? According to Cartesian philosophy, artificial organisms fall in the same category as organisms produced by evolution: we are not recreating nature. The difference between artificial organisms and natural organisms lies in their respective purposes. Natural organisms have an intrinsic purpose; they manifest and pursue their own aims (growth, adaptation, reproduction, etc.). In contrast, the aims of synthetic organisms are entirely defined by human beings. Because synthetic biology separates living organisms from their own evolutionary histories, transforming them in accordance with human wishes, it has distinct goals from those of animal domestication and artificial selection, which seek to shape naturally evolved organisms to meet human needs.

Based on the January 2014 Opinion (on synthetic biology) published by the Common Advisory Committee for Ethics in Agricultural Research