Pluralistic Perspectives on Biosafety Norms

The value of biosafety has shown many different meanings throughout the course of our investigation. This plurality soon became apparent from the norms ascribed by our participants to biosafety. In Table 3 we present our findings of four main norms of biosafety: (I) Compliance with regulation; (II) Evaluation of microbes; (III) Responsibility; and, IV) Assessment of risk and uncertainty.Table 3

Main norm groups representing the different stakeholders’ views of the value of biosafety together with the corresponding design approaches. Each group is accompanied by a representative quote and sources supporting or stating each of the design approaches are shown in the last column with a numerical code (I = industry, A = academic, R = regulation, policy or technology transfer representative)

Norms	Design approach	Description	Source
Compliance with regulation:“The physical containment is sufficient to comply with regulations, and that is the key thing, we need to comply with regulations.” (I2)	Biological containment	Use of hosts microorganisms with a reduce host range, with natural or genetically modified characteristics that diminish their invading capacity or virulence, self-inactivating vectors, etc.	I3, I4, I6, R1, A4
	Physical containment	All the physical barriers that prevent or minimize the escape of the microorganisms from the controlled settings	I2, I3, I6, R2, A4, I8
	GMO-free products	Separation of producer and products and inactivation of the biomass	I3, I4, I5, A2, R1, I8
	Historical argument of biosafety	Engineered strains retain the biosafety category granted to their ancestors	I2, I7, A3, I8, I9
	Regulation	Biosafety committees that take care of specific controls and standards. Additional approvals and bigger dossiers than other bioprocesses	I2, I5, I6, I7, A3, R1, R2, I8, I9, R4
Evaluation of microbes:“The whole thing is that you should really study your microorganisms carefully and monitor things and be aware of what could happen.” (A4)	Study of introduced genetic elements	Monitorization of stability and mobility of introduced genetic elements	I3, I9
	Sequencing	Sequence check of plasmids and full genome	I4, I5, I6, I7, I9
	Other assays	Growth, productivity and fitness assays	I5, I7, I8, I9
Responsibility:“That's why the Safe-by-design concept try to promote a proactive approach by actors so that the government doesn't need to solve problems afterwards, but that the actors who develop something, who innovate, who develop a new technology or new application, think about the safety aspects during that process.” (R2)	Multi-actor responsibility	Proactive responsibility at all stages of the process. Safe-by-design framework	I4, R2, R3
	Cellular barcoding	Accountability through identification of labelled cells through space, time and even cell division which allows the instant access to all the information associated to a particular construct including its origin, its nature, if it is sensitive to antibiotics, what countermeasures one could take, etc.	A3, I9
Assessment of risk and uncertainty:“If we work in a reasonably well-established organism like E. coli or Saccharomyces, I would say that we do not do any test to see whether it's safe or not. We basically go off the literature where others have done those tests already.” (I8)	Domestication	Human selection of strains to obtain cultivated variants that thrive in artificial niches and meet specific requirements. During this process, microbes become more efficient in consuming particular nutrients, coping with research- or industry-specific stress factors, and producing the target compounds, but this usually comes at the cost of a dramatic decrease of fitness in their natural environment	I4, I6, I9, R1
	Scientific uncertainty	Uncertain risks beyond the imposed norms and extra measures	I2, I4, I6, A3, A4, R2, I8, R3
	Non-fitting assessment	Current regulation does not cover all the aspects of the technology	A2, R2

The norms collected in Table 3 reflect the plurality of the different understandings of biosafety encompassing categories that sometimes do not even vary along the same underlying dimensions (some of them are rules, some are individual practices, and some are general assumptions). While most of them could be considered complementary and particular facets of the value, some of them appear contradicting, which originates the possibility of value tensions (e.g., historical argument of biosafety vs. scientific uncertainty).
Genetic safeguards are not found in our empirical investigation. However, one could envision genetic safeguards as part of the biological containment (norm of compliance), or as part of multi-actor responsibility by giving deliberate attention to biosafety since the conception of a strain’s engineering (norms of responsibility).