In the last decade, we have witnessed how standardisation has paved the progress in several scientific disciplines. But regarding synthetic biology, it seems to be more difficult to define and fully implement. This brings us to the next question: is standardisation alone enough to backbone the technologies that are born within synthetic biology?
“No matter how hard we try, biology will never be an exact science,” says Enrique Asín, last year-PhD candidate in SynBio at Wageningen University, who has brought this conversation to his thesis. He and his colleagues argue in a recent article [1] that standardisation in biology is essential but needs a different consideration than when applied to other areas.
“A high degree of standardisation has been already achieved with genetic elements that have been deeply studied during the years, such as promoters, RBSs and reporter proteins, but things get complicated with complex genetic circuits or metabolic pathways,” he claims: “The keys for standardising are simplicity and the highest possible understanding of our systems, and generally, we still don’t fully understand most of what is happening in the cells.”
Standardisation seeks to develop tools that can act as common words and meanings for everyone working in SynBio. But the construction and manipulation of biological systems might be unique enough to require a more complex consideration. Here is where the concept of contextualisation emerges.
The devil’s in the detail
Linguist Jonathan Culler wrote that “we might say that meaning is determined by context, since context includes the rules of language, the situation of the author and reader, and anything else that might conceivably be relevant”. Following this analogy, contextualising in SynBio could be defined as acknowledging the details of a problem as requiring specific approaches, solutions and collaborations. It implies looking into the particularities of a given question to bring a more tailored response. These details could be either scientific, referring to whether the application under development is for healthcare, industry or environment; or social, such as identifying the relevant stakeholders, policymakers, etc.
Taking these details into account may bring some advantages when facing challenges in SynBio. For instance, due to the high interdisciplinarity of the field, a contextualised problem may facilitate the participation of key stakeholders and other external experts whose feedback could positively impact the project.
Context is not new to biology [2]. There are some central biological components that are context-dependent [3] [4], and this is considered one of the main barriers that limits our capacity to develop common standards. For instance, Asín is currently applying this concept to a specific area of SynBio which is biosafety [1]. In this case, the procedure to develop genetic safeguards to prevent undesired behaviour of customised cells is highly optimised when context is addressed. It makes sense since a security system made for an application in healthcare might require a different scientific or social approach than one made for industry.
Not everything goes
Then, if context already has a relevant place within SynBio, what could be its relationship with standardisation?
By looking at the purpose of contextualisation, that is, to adapt our efforts in devising solutions for specific contexts, it may seem a bit antagonistic to the basis of standardisation, which tries to define all-rounder modules. But is this really the case?
“Contextualisation is nothing else but a complement of standardisation,” Asín says. He suggests that contextualization is not necessarily an opposite force in the way of standardization but another layer to consider in this challenge. “While the latter is theoretically meant to encompass any possible situation, the former tries to focus on those more related to the conceptual nature of your experiments. One could design a biological device intended to work in many applications and organisms, but it is unlikely that it behaves or performs equally in all of them.”
“Along this line, the contextualisation approach reduces the spectrum of application by zooming in on those application contexts where the device might be more relevant. This is of course not necessary for every biological research but comes handy when an innovation needs to transcend and be assessed for real-world applications.”
It is worth noting that contextualisation should not be seen as a master key to unlock every single issue that is currently slowing down standardisation in SynBio. Focusing too much on the details could make us quickly discard valuable options early on, prioritizing just some of them. This phenomenon could also create a tendency to drive a strong “case-by-case” mindset, which could become an issue if we do not want to lose standardisation as one of the central tenets of SynBio.
As Asín and his colleagues comment in their article: “while contextualization does not provide all the answers, it could support synthetic biologists in devising appropriate and actionable roadmaps for agreed application context.”
References
[1] Kallergi, A., Asin‐Garcia, E., Martins dos Santos, V. A., & Landeweerd, L. (2021). Context matters: On the road to responsible biosafety technologies in synthetic biology. EMBO reports, 22(1), e51227.
[2] Beal, J., Goñi‐Moreno, A., Myers, C., Hecht, A., de Vicente, M. D. C., Parco, M., … & Porcar, M. (2020). The long journey towards standards for engineering biosystems: Are the Molecular Biology and the Biotech communities ready to standardise?. EMBO reports, 21(5), e50521.
[3] Carr, S. B., Beal, J., & Densmore, D. M. (2017). Reducing DNA context dependence in bacterial promoters. PloS one, 12(4), e0176013
[4] Poelwijk, F. J., Krishna, V., & Ranganathan, R. (2016). The context-dependence of mutations: a linkage of formalisms. PLoS computational biology, 12(6), e1004771.
[5] Asin-Garcia, E., Kallergi, A., Landeweerd, L., & Dos Santos, V. A. M. (2020). Genetic safeguards for safety-by-design: so close yet so far. Trends in biotechnology, 38(12), 1308-1312.