On the Track to Creating Life: Synthetic Biology

Over recent decades, scientific research and biotechnological capabilities have made deeper and deeper interventions into living organisms possible. Huge advances in nanobiotechnology and systems biology, which increasingly benefit from the potential of ongoing digitalization, have fueled the emergence of synthetic biology and raised high expectations that humans may perhaps be able to create living systems from scratch in some not too far distant future. After more than 200 years of synthetic chemistry and about twenty years of synthetic nanoparticles, a new wave of human "creation” is ongoing. The question of whether and how such developments can be performed in a responsible manner has been raised in an intensified form since about the late 2000s, building on earlier reflections on the ethical issues raised by biotechnologies and genetically modified organisms (GMO).

This chapter reviews the state of the art of the responsibility debate regarding synthetic biology and extends this by applying the framework of problem-oriented ethics and responsibility (Chap. 3). First, a brief introduction of synthetic biology and its roots in nanobiotechnology will be given (Sec. 4.1). Second, the societal and ethical debate, including considerations of opportunities and risks, will be reviewed, based on the results of projects on ethical,

Living Technology: Philosophy and Ethics at the Crossroads Between Life and Technology

Armin Grunwald

Copyright © 2021 Jenny Stanford Publishing Pte. Ltd.

ISBN 978-981-4877-70-1 (Hardcover), 978-1-003-14711-4 (eBook)

www.jennystanford.comlegal, and social aspects (ELSA) and on technology assessment (TA) studies (Sec. 4.2). The third part will systematically elaborate on the ethical issues, which demarcate normative uncertainty at the occasion of focal items of ethics, such as the moral status of created organisms (Sec. 4.3). The responsibility configuration of synthetic biology through the lens of the EEE model developed in the preceding chapter will be analyzed in Sec. 4.4. Finally, issues beyond consequentialist ethics will be addressed: Sec. 4.5 includes a hermeneutic consideration of the changing relationship between technology, nature, and life, considering implications and repercussions for the notion and understanding of life itself.

Synthetic Biology

Synthetic biology turned into a vibrant field of scientific inquiry and ethical debate around the year 2005 (Giese et al., 2014). In 2010, Craig Venter, one of the pioneers of synthetic biology, announced that he had successfully implanted artificial DNA into a bacterium. Synthetic biology then rapidly became known to the public (Synth-Ethics, 2011) and has led to a series of activities on its ethical, legal, and social implications (ELSI; cp. Sec. 4.2) as well as to responsibility reflections and analyses (Sec. 4.4).

The combination of engineering at an extremely small scale, e.g., by nanotechnology (see below), and biology, in particular molecular biology and systems biology, is at the roots of synthetic biology. Since the diameter of DNA, a typical object of technical operation, is approximately two nanometers (nm), synthetic biology can be considered "a specific discipline of nanobiotechnology" (de Vriend, 2006, 23; see below). In turn, synthetic biology can also be viewed as the continuation of molecular biology using the means of nanobiotechnology. In the meantime, synthetic biology has also become a sub-discipline of biology. While nanotechnology involves the development of materials and machines at the nanoscale, synthetic biology builds on the insight that nature already employs components and methods for constructing something similar to machines and materials at very small scales. By employing off-the-shelf parts and methods already used in biology and by developing new tools and methods, synthetic biologists hope to develop a set of tools to accelerate deepening human influence on living systems by new technology (Synth-Ethics, 2011).

Synthetic biology differentiates between an approach that uses artificial arrangements of molecules to (re)produce biotic systems and one that combines elements of classical biology to form new systems that function in amanner beyond pre-existing nature (Benner and Sismour, 2005). The motivation behind this is to create artificial or technically modified forms of life that are partially equipped with new functions. The major question of synthetic biology is: "how far can it [life] be reshaped to accommodate unfamiliar materials, circumstances, and tasks?" (Ball, 2005, R3). Examples range from the design of artificial proteins, to the creation of virus imitations or the reprogramming of viruses, and even extend to attempts to program cells to perform desired functions (Ball, 2005; Benner and Sismour, 2005, 534-540).

Various definitions have been suggested for synthetic biology, all of which point in the same direction despite different accentuations. Accordingly, synthetic biology is seen as (cp. also Pade etal., 2014, for an in-depth consideration of several novelties of synthetic biology):

• • The design and construction of biological parts, devices, and systems and the redesign of existing, natural biological systems for useful purposes (LBNL, 2006).
• • The design and synthesis of artificial genes and complete biological systems and the modification of existing organisms, aimed at acquiring useful functions (COGEM, 2006).
• • The engineering of biological components and systems that do not exist in nature and the re-engineering of existing biological elements; this is determined by the intentional design of artificial biological systems, rather than by the understanding of natural biology (Synbiology, 2005).
• • The use of a mixture of physical engineering and genetic engineering to create new (and therefore synthetic) life forms (Hunter, 2013).
• • Applying the engineering paradigm of systems design to biological systems in order to produce predictable and robust systems with novel functionalities that do not exist in nature (EC, 2016).

All these definitions touch upon a common concept: the creation of new biological systems via the synthesis or assembly of artificial and natural components. To do this, synthetic biology needs to encompass a broad range of methodologies from various disciplines, such as genetic engineering, molecular biology, systems biology, membrane science, biophysics, chemical and biological engineering, electrical and computer engineering, control engineering, and evolutionary biology ("Synthetic biology." Wikipedia, https:// en.wikipedia.org/wiki/Synthetic_biology; accessed 20 May 2020).

The epistemic approach of synthetic biology regards biotic units (living organisms) as complex technical relationships, which can be broken down into simpler technical ones. This approach could be named "deconstructing life” following the model of technology (de Vriend, 2006). Living systems are examined within the context of their technical function, and cells are interpreted as machines - consisting of components, analogous to the components of a machine, which have to co-operate in order to fulfill the overall function. For example, proteins and messenger molecules are understood as such components that can be duplicated, altered, or newly compounded in synthetic biology. A modularization of life is thereby made, as well as an attempt to identify and standardize the individual components of life processes (Danchin, 2014). In the tradition of technical standardization, gene sequences are saved as models for various cellular components of machines. While this is still, so to speak, a form of analytic biology, it becomes synthetic as soon as the knowledge about individual processes of life obtained from technical modeling is combined with the corresponding experiments and utilized so that certain useful functions can be achieved (Schwille, 2011). Following design principles of mechanical and electrical engineering, the components of living systems should be put together according to a building plan in order to obtain a functioning whole. The recombination of different standardized bio-modules (sometimes called "bio-bricks") allows for the design and creation of different living systems. Artificial cells based on such components and micro-machines are projected that can, for example, process information, manufacture nanomaterials, or make medical diagnoses. Entirely in the tradition of mechanical and electric engineering, such machines are supposed to be built part by part according to a design that is drafted top-down in order to enable useful purposes: "Seen from the perspective of synthetic biology, nature is a blank space to be filled with whatever we wish” (Boldt and Müller, 2008, 388). With the growing collection of modules, out of which engineering can develop new ideas for products and systems, the number of possibilities grows exponentially. The result is supposed to be a functioning entity:

Engineers believe it will be possible to design biological components and complex biological systems in a similar fashion to the design of chips, transistors, and electronic circuits (de Vriend, 2006,18).

The combination of knowledge about molecular biology and genetic techniques with the opportunities offered by nanotechnology is decisive for scientific and technological progress. The prerequisite for a precise design of artificial cells would be a sufficiently thorough understanding of all the necessary subcellular processes and interactions. In this respect, synthetic biology is still at an early stage of development. Many research fields contribute to improving the state of the art, with nanobiotechnology being among the major predecessors (Schmid et al., 2006).

The concept of nanobiotechnology, or bionanotechnology, (cp. Jotterand, 2008a) was coined in the context of the National Nanotechnology Initiative of the United States (NNI, 1999). Its point of departure is the observation that basic life processes take place at a nanoscale, which is the size of life's essential building blocks, such as proteins. At this level, nanotechnology could make it possible to engineer cells by networking natural biological processes with technical ones. Visions of nanomachines at the level of cellular and subcellular processes take the form of mechanisms for producing energy, molecular factories, and transport systems or high-capacity data storage and data reader systems. The language of engineering is extended to processes and objects of life at the nanolevel:

To a large extent, the metaphors in synthetic biology are borrowed from the fields of engineering, construction and architecture, electrotechnics, information theory or information technologies (IT), computer science, design and theology (Funk et al., 2019,179).

Examples of such uses of language refer to hemoglobin as a "vehicle,” to adenosine triphosphate synthase as a "generator,” to nucleosomes as "digital data storage units," to polymerase as a "copier,” and to membranes as “electrical fences." Functional biomolecules act as components for gathering and transforming light, or as signal converters, catalysts, pumps, or motors:

The fact that biological processes are in away dependent on molecular machines and clearly defined structures shows that building new nano-machines is physically possible (Kralj and Pavelic, 2003, 1011; cp. also Danchin, 2014).

A characteristic example is the attempt to create technical replicas of photosynthesis (Cheng and Fleming, 2009; acatech, 2018). Plants and some forms of bacteria assure their energy supply by means of photosynthesis (Blankenship, 2014). Sunlight is used to synthesize complex carbohydrates from carbon dioxide and water, which serve both for energy storage and as energy supply. In contrast to current photovoltaic cell technology, this principle even functions in diffuse or very weak light. The idea of using the principle of photosynthesis, as it has developed in the course of evolution, to technically ensure an energy supply for humans is exceptionally appealing (acatech, 2018). Energy supplied on the basis of this principle would be CO₂ neutral, would be easily storable, could be produced in a decentralized fashion, would be practically inexhaustible, and would not produce any problematic waste (Faunce et al., 2013). Nanobiotechnology provides the techniques needed to understand the natural processes at the molecular level and possibly to be able to replicate them. It concentrates on replicating the simpler manner of functioning in bacteriochlorophyls, relying on the principle of self-organization for the formation of the corresponding nanoscale structures (Balaban and Buth, 2005). There is hope that such research can contribute to the development of engineered biosensors and artificial antennas that can even function in weak and diffuse light (French et al., 2014). They could then be useful for the design of hybrid solar cells based on economical polymer technologies (Balaban and Buth, 2005, 207). Such research is however still entirely in the sphere of basic research (acatech, 2018; cp. the references provided there). The point is to understand essential processes in the context of their technical functioning (Erb and Zarycki, 2016). Designations such as "light harvesting complex" or "proton pump" demonstrate the technical view of photosynthesis on processes stemming from life (Cheng and Fleming, 2009).

Approaches for utilizing the principles of evolution to achieve certain new effects are another approach in synthetic biology. For example, cells could be subject to the pressure of artificial evolution by turning off the genetic sequences responsible for the building of certain amino acids. By adding chemical substances that are chemically sufficiently similar to the missing amino acids, the cell can be brought to use the substitutes in place of the amino acids. The result of this is a cell with modified properties. Here there is a tight interface with systems biology (Bruggeman and Westerhoff, 2006; Boogerd et al., 2007), in which the complex interaction of the many individual processes is to be understood as a complex entity:

Systems biology is crucial to synthetic biology. It includes knowledge about the natural basic biological functions of RNA and DNA sequences in information storage, energy supply, membrane functions, cell structure, cell-to-cell signalling, gene regulation (gene expression), and metabolic functions in natural systems [...] (de Vriend, 2006, 23).

The traditional self-understanding of biology, which is molded by the natural sciences, aims to understand vital processes. In epistemic respect, a widespread understanding among synthetic biologists is that understanding life, as is the traditional aim of biology, will be fully achieved only if biology becomes able to rebuild life. Because rebuilding existing life and inventing new types of life requires the same type of knowledge, the aim of understanding leads to the capability of creating life by synthetic biology (Ball, 2005; Woese, 2004). Synthetic biology as an engineering science is about a new invention of nature and the creation of artificial life on the basis of knowledge about traditional and "natural" life. It is no longer satisfied with investigating life which already exists but aims at redesigning or even reinventing nature. Early successes have been reported (cases taken from Wikipedia):

• A completely synthetic bacterial chromosome was produced in 2010 by the team of Craig Venter and introduced to genomically emptied bacterial host cells (Gibson et al., 2010).

• In 2019, researchers reported the creation of a new synthetic (possibly artificial) form of simplified but viable life (Fredens etal., 2019).

This change of perspective from understanding to creating life transforms biology into a technical science (de Vriend, 2006) that embodies the dual strands of cognition and design and that is subordinate to the primacy of design goals. This even holds at the current stage of development, with only a few applications. Just as in the classical technical sciences, synthetic biology is more "know how” than "know that” or "know why" (Pade et al., 2014). Though the latter are both required for providing "know how,” they only keep an instrumental function in the research processes of synthetic biology:

Although it can be argued that synthetic biology is nothing more than a logical extension of the reductionist approach that dominated biology during the second half of the twentieth century, the use of engineering language, and the practical approach of creating standardised cells and components like in an electrical circuitry suggests a paradigm shift. Biology is no longer considered "nature at work", but becomes an engineering discipline (de Vriend, 2006, 26).

Therefore, synthetic biology can be subsumed under the concept of technosciences (Latour, 1987; Asdal etal., 2007), in which the area of life is modelled as an ensemble of machines (Danchin, 2014). In this new form of biology, "the pre-existing nanoscale devices and structures of the cell can be adapted to suit technological goals” (Ball, 2005, Rl). This position has consequences for the applicability of the consequentialist paradigm of the ethics of technology (Sec. 3.3.2) and assignments of responsibility (see Sec. 4.4).