Rapport 72827 ... Read more

Recent advancements in synthetic biology fundamentally challenge the traditional definition of an ‘organism’ and the regulatory use of the term ‘biological entity’. Developments such as gene editing, organoids, DNA computing, and synthetic cells increasingly blur the boundaries between living and non-living systems, prompting critical reassessment of foundational biological and legal concepts.

Current European and Dutch legislation, including Directive 2009/41/EC and the GMO Decree, defines organisms as "biological entities capable of replication or of transferring genetic material". However, the term ‘biological entity’ itself remains undefined. Scientific advisory bodies like COGEM (the Netherlands Commission on Genetic Modification) have long recognized that synthetic biology renders current definitions inadequate. Their reports consistently highlight how novel biological constructs, such as synthetic cells and biohybrid systems, do not align with traditional concepts of life, yet demand regulatory oversight.

Additionally, while the terms ‘organism’ and ‘biological entity’ are both used in law, their meanings can diverge significantly in scientific discourse. Legal definitions are often structured around risk and containment rather than biological accuracy, creating friction between regulatory objectives and scientific realities. For example, while scientists often exclude viruses from the category of organisms due to their host-dependence, legal frameworks classify them as biological entities, and thus subsequently as organisms for risk management reasons. ... Read more

This paper showcases a project involved in the international Genetically Engineered Machines (iGEM) competition – a competition dedicated to the advancement of synthetic biology – executed at Delft University of Technology, the Netherlands. Through this case, we illustrate how Value Sensitive Design (VSD) and Safe by Design (SbD) are embedded in education associated with iGEM to arrive at a safe and responsible project design by integrating values and, particularly, the value of safety. As particularly SbD is still quite generally described in literature, we aim to make SbD more tangible to peers, and to inspire other iGEM teams and educators. In addition, we reflect on VSD and SbD in the context of Responsible Research and Innovation and provide guidelines for other iGEM projects to implement VSD and SbD approaches in their designs. To conclude, we explore if, and how SbD and iGEM projects could function as anticipatory governance tools for synthetic biology. ... Read more

In recent years, the relationship between academia and the fossil fuel industry has become a focal point of intense debate. This concern arises from the fear that corporate funding might skew research activities. A significant development in this area is the adoption of policies by a Dutch university, and discussions in several others, prohibiting research funded by the fossil fuel industry. These policies aim to safeguard academic freedom and integrity. Despite this, there has been little discussion on the myriad challenges, implications, and possible unintended consequences, particularly in the realm of safety-and-security research. As such, this manuscript delves into the complex transition towards a fossil-fuel-free society, examining it through the lenses of safety science and sociotechnical systems. It emphasizes the vital importance of collective responsibility in ensuring systemic safety and security as we navigate towards achieving the sustainable development goals. This journey requires a delicate balance between the objectives of safety and sustainability, along with a deep understanding of the security implications of decreasing our dependence on the fossil fuel industry. The strategy of distancing academic research from fossil fuel industries, commonly seen as a positive step, also demands a nuanced consideration of its broader impacts, including the setting of precedents for addressing other existential and systemic risks. Instead, we argue for the establishment of robust governance structures rooted in restorative justice principles. Such frameworks can facilitate productive dialogue with underrepresented groups, motivate the fossil fuel industry towards sustainable practices, and safeguard the integrity of scholarly research. This approach not only addresses immediate concerns related to fossil fuels but also lays the groundwork for a more inclusive and equitable model of climate risk research, essential for tackling the multifaceted challenges of our era. ... Read more

Dit rapport richt zich op de implementatie van het Safe-by-Design (SbD)-principe binnen de context van omgevingsveiligheid in de chemische industrie. SbD is een opkomende methode voor risicomanagement dat veiligheid vanaf de ontwerpfase integreert in technologische en industriële systemen door ook naar onzekerheden te kijken. We spreken van onzekerheden in veiligheidsmanagement als de aard, de kans, de omvang of het effect van risico’s niet volledig bekend of voorspelbaar is. Door het toepassen van SbD, en dus onzekerheden mee te nemen in ontwerpen en procesbeheer, pogen we onzekerheden terug te brengen naar een beheersbaar risico. Deze methode is bijzonder waardevol in een tijd waarin complexe systemen, zoals waterstof-infrastructuur, een cruciale rol spelen in de energietransitie.

Het rapport benadrukt dat traditionele methoden voor risicomanagement, zoals methoden die zich vooral op kwantificeerbare, ‘harde cijfers’ focussen, sterk afhankelijk zijn van beschikbare historische data. Echter, van nieuwe technologieën en industriële processen hebben we vaak niet dergelijke data voorhanden, en dus schieten deze methoden tekort bij het omgaan met onzekerheden en nieuwe risico’s. Daarnaast richten huidige methoden voor veiligheidsmanagement in de chemische industrie zich voornamelijk op het verlagen van risico’s, bijvoorbeeld door het toepassen van de inherente veiligheidsprincipes (ISPs), en zijn dus vooral toegespitst op de ‘risicobehandeling’-fase in risicomanagement. In dit rapport kijken we breder naar de volledige risicomanagementcyclus, en worden mogelijke onzekerheden in elke fase van de cyclus bekeken. SbD biedt richtlijnen om veiligheid een integraal onderdeel van het gehele risicomanagementproces te maken.

Achtergrond en doel
Onzekerheden vormen een grote uitdaging in elk stadium van risicomanagement. Tijdens de contextbepaling kan het ontbreken van historische data leiden tot onvolledige risico-identificatie en verkeerde systeemgrenzen. In de analysefase kan de ernst van risico’s worden onderschat, door modellen met lage betrouwbaarheid of door een gebrek aan deskundige kennis. Ook in de evaluatie- en behandelingsfase spelen onzekerheden een rol, vooral wanneer criteria voor risico-acceptatie vaag zijn of wanneer besluitvorming wordt beïnvloed door menselijke (vaak onbewuste) vooroordelen. Het rapport stelt dat deze tekortkomingen beter kunnen worden aangepakt door SbD-principes zoals het voorzorgsprincipe en systeemdenken te integreren in risicomanagement. Door te plannen voor worst-case scenario’s en risico’s met onzekerheden proactief te benaderen, kunnen organisaties niet alleen voldoen aan wettelijke eisen, maar deze ook overstijgen (beyond compliance) om veerkrachtige systemen te ontwikkelen.

Safe-by-Design als mentaliteit: van afvinken naar anticiperen
SbD vraagt om meer dan het volgen van stappenplannen of beslisbomen. In een technologische en maatschappelijke context die steeds complexer en onzekerder wordt volstaat het niet om veiligheid ‘af te vinken’. SbD vergt een fundamentele mentaliteitsverandering: weg van compliance als einddoel, en richting veiligheid als een voortdurend proces van anticiperen, kritisch nadenken, afstemmen en iteratie.

Verschillende SbD-principes kunnen ingeschakeld worden om onzekerheden te adresseren in elke stap van de risicomanagement cyclus. Het voorzorgsprincipe helpt bij het omgaan met onzekerheden door uit te gaan van worst-case scenario’s (waarbij de nadruk ligt op de gevolgen in plaats van op de (onzekere) kans) en extra veiligheidsmarges waar kennis nog beperkt is. Systeemdenken binnen SbD betekent verder kijken dan de grenzen van de eigen installatie en anticiperen op kettingreacties en wisselwerkingen binnen het grotere systeem. Ook neemt systeemdenken de complexiteit van moderne sociaal-technische systemen in beschouwing, met aandacht voor de interactie tussen technische factoren, mensen en de omgeving.

SbD houdt een integrale aanpak in waarbij bredere maatschappelijke en langetermijn risico’s worden meegenomen. Het expliciet meenemen van deze risico’s draagt bij aan een meer realistische inschatting van risico’s in een context van onzekerheid en complexiteit. Dit vereist ook een levenscyclusbenadering waarin veiligheid verankerd is van ontwerp en constructie tot onderhoud en ontmanteling. Stakeholderparticipatie speelt hierin een centrale rol: door maatschappelijke zorgen en lokale kennis vanaf het begin te integreren, ontstaan zowel beter draagvlak als scherpere risicobeoordelingen. Ook samenwerking is essentieel om verschillende invalshoeken mee te nemen, en objectiviteit te vergroten door meerdere experts onafhankelijk een oordeel ta laten vellen. Overheden kunnen deze samenwerking actief ondersteunen: enerzijds door het verspreiden van kennis over de beste beschikbare technologieën voor onder meer inspectie en monitoring, anderzijds door het stimuleren van kennisdeling binnen de sector.

Een iteratieve en dynamische aanpak is cruciaal binnen SbD, waarbij nieuwe informatie voortdurend wordt teruggekoppeld om zo risico’s continu te actualiseren. Door actuele inspectiedata te vergelijken met ontwerpmodellen kunnen aannames worden getoetst en waar nodig worden bijgesteld, om zo onzekerheidsmarges te verkleinen.

Door SbD-principes in elke stap van de risicomanagementcyclus toe te passen worden onzekerheden teruggebracht tot beheersbare risico’s. Dit leidt niet alleen tot minder incidenten, maar ook tot hogere betrouwbaarheid en beschikbaarheid van installaties en versterkt maatschappelijk vertrouwen. SbD verschuift de focus van ‘veilig genoeg volgens de norm’ naar ‘veilig omdat het duurzaam en verantwoord is’.

Overheden spelen een cruciale rol in het toewerken naar de SbD-mentaliteit. Zij dienen beleidskaders te ontwikkelen die innovatie bevorderen, zorgen voor naleving van veiligheidsnormen,
en aansporen tot anticiperen van nieuwe risico’s met bijhorende onzekerheden.

Opdrachtgever Ministerie van Infrastructuur en Waterstaat (IenW) ... Read more

This essay describes the competencies that chemical engineers need to ‘do chemistry differently’: they need to be able to question their own assumptions, collaborate with other disciplines and integrate safety and environmental performance in the design of chemicals and chemical products. ... Read more

In the built environment, often too much focus is put on compliance instead of seeking the optimal fire-safety solution for the building. Because of a lack of tangible incentives for building owners, the benefits of implementing fire safety measures and their societal contribution are often not recognized and therefore, not considered. By means of a literature review and a survey, we have indicated necessary fire-safety related attributes and tool features and analyzed the currently available fire risk assessment tools. This study shows that a limited number of these tools can provide a partial fire risk analysis of a building. A total of 26 tools were found. No tools were found that included all the identified fire consequence-related attributes to ensure fire-safe buildings. However, we did identify 11 tools that have the potential to assess between 32 % and 52 % of the found attributes of building fire safety. To stimulate the development of such tools, this paper provides 12 factors by which to assess fire risk assessment tools – quantifying the overall ‘quality’ of the assessment tool – which can incentivize industry to refine the existing ones with enhanced predictability of the potential consequences of fire incidents. ... Read more

This work explores resource recovery coupled to seawater desalination in small islands. As small islands depend on seawater desalination for water access, they make an excellent ground for exploring the trade-offs associated to resource recovery, like potential economic gains, energy use, and environmental impacts. Here, we investigated these tensions in the context of Lampedusa, in Italy. We then developed and evaluated scenarios for the recovery of additional water, Mg, and other resources from brines, to identify if and how resource recovery is an interesting approach for the island vis-à-vis these tensions. We have found that the potential to increase water production with water recovery from brine is an interesting alternative for small islands, especially when harnessing waste heat. However, while some technologies offer possibilities for recovering additional resources, in places like small islands the potential benefits from additional recovery do not seem to justify the costs to the local system. ... Read more

In September 2015, the United Nations General Assembly established the 2030 Agenda for Sustainable Development, which includes 17 Sustainable Development Goals (SDGs) [...]. ... Read more

Emerging applications of biotechnology such as new genomic techniques may give rise to new uncertainties and uncertain risks. Particularly the increased complexity and limited knowledge of possible risks associated with these new
techniques, make it currently impossible to perform an adequate environmental risk assessment. As a result, there is a risk that such techniques don’t get beyond experiments demonstrating the proof of principle, stifling their further
development and implementation. To break free from this deadlock, wemust be able to learn what such uncertainties and uncertain risks entail, and how they should be assessed to ensure safe further development. To shape a responsible learning environment to explore uncertainties and uncertain risks, we have organized five stakeholder workshops. By means of a case about the genetic engineering of plants’ rhizosphere–an application abundant with uncertain risks–we identified tensions between different stakeholder groups and their different estimates of uncertainties and uncertain risks. Based upon derived insights, we developed a tool–a script for researchers to organize a
stakeholder workshop–that enables a constructive discussion about emerging risks with a broad range of stakeholders. Thereby, the script provides a step-by-step approach to identify uncertainties, develop anticipatory strategies and adaptations in (experimental) research designs to lower or mitigate the earlier
identified uncertainties, and helps to identify knowledge gaps for which (additional) risk research should be set up. ... Read more

The current regulatory regime regarding GMOs within the Netherlands and Europe does ensure safety but struggles in balancing this notion with innovation. In particular, the way the Precautionary Principle (PP) is operationalized in GMO legislation has resulted in a highly precautionary culture in which there is little room to conduct research with associated uncertain risks or uncertainties – it has resulted in a culture of compliance. Although the debate on how ‘new’ genetic engineering techniques such as CRISPR should be assessed in comparison to recently exempted techniques is ongoing within the European Union (EU), this might not have any consequences for GMO regulation at all. These issues do not only stifle innovation but also illustrate that the current regime is not resilient in dealing with emerging techniques. To break free from the impasse between safety and innovation, researchers should be able to learn what uncertain risks entail, for instance, through Safe-by-Design (SbD).
The main question addressed in this thesis is: “How to create an environment that is suitable to learn safely and responsibly what uncertain risks associated with emerging biotechnologies entail?”. I conclude that to enable responsible learning by means of SbD, 3 conditions are needed; regulatory flexibility, co-responsibility and awareness. Thereby, SbD could be a suitable approach to arrive at responsible learning, given that the 3 conditions are met. If not, SbD provides guidelines to lower or mitigate known risks but fails to provide a step-by-step approach to gradually learn what uncertain risks entail. This will leave a knowledge gap between known and uncertain risks which stifles innovation and hinders risk management in ensuring future safety for people, animals and the environment.
... Read more

The increasing societal demand for safer, biobased products, and processes
creates opportunities for industrial biotechnology and chemistry. To succeed,
controlled learning about new emerging risks is crucial but both fields endure
difficulty in doing so by their respective regulation and risk management culture. ... Read more

Veiligheid staat hoog in het vaandel in het huidige risicomanagement van biotechnologie. Maar dit leidt ook tot een restrictief regime waarin weinig ruimte is om te leren over onzekere risico’s. Om binnen de biotechnologie innovaties mogelijk te maken die bijdragen aan maatschappelijke doelen en tegelijkertijd veilig zijn, moeten we naar een cultuur waarin ruimte is voor verantwoord leren over risico’s. Hoe doen we dat? ... Read more

Although both the Inherent Safety Principles (ISPs) and the Safe-by-Design (SbD) approach revolve around the central value of safety, they have a slightly different focus in terms of developing add-on features or considering initial design choices. This paper examines the differences between these approaches and analyses which approach is more suitable for a specific type of research—fundamental or applied. By applying the ISPs and SbD to a case study focusing on miniaturized processes using Hydrogen Cyanide, we find that both approaches encounter internal value-conflicts and suffer from external barriers, or lock-ins, which hinder implementation of safety measures. By applying the Technology Readiness Levels (TRLs), we gain insight in the matureness of a technology (thereby distinguishing fundamental and applied research) and the extent of lock-ins being present. We conclude that the ISPs are better able to deal with lock-ins, which are more common in applied research stages, as this approach provides guidelines for add-on safety measures. Fundamental research is not subject to lock-ins yet, and therefore SbD would be a more suitable approach. Lastly, application of either approach should not be associated with a specific field of interest, but instead with associated known or uncertain risks. ... Read more

Genetic engineering techniques (e.g., CRISPR-Cas) have led to an increase in biotechnological developments, possibly leading to uncertain risks. The European Union aims to anticipate these by embedding the Precautionary Principle in its regulation for risk management. This principle revolves around taking preventive action in the face of uncertainty and provides guidelines to take precautionary measures when dealing with important values such as health or environmental safety. However, when dealing with ‘new’ technologies, it can be hard for risk managers to estimate the societal or environmental consequences of a biotechnology that might arise once introduced or embedded in society due to that these sometimes do not comply with the established norms within risk assessment. When there is insufficient knowledge, stakeholders active in early developmental stages (e.g., researchers) could provide necessary knowledge by conducting research specifically devoted to what these unknown risks could entail. In theory, the Safe-by-Design (SbD) approach could enable such a controlled learning environment to gradually identify what these uncertain risks are, to which we refer as responsible learning. In this paper, we argue that three conditions need to be present to enable such an environment: (1) regulatory flexibility, (2) co-responsibility between researchers and regulators, and (3) openness towards all stakeholders. If one of these conditions would not be present, the SbD approach cannot be implemented to its fullest potential, thereby limiting an environment for responsible learning and possibly leaving current policy behind to anticipate uncertain risks. ... Read more

Advanced gene editing techniques such as Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)/Cas have increased the pace of developments in the field of industrial biotechnology. Such techniques imply new possibilities when working with living organisms, possibly leading to uncertain risks. In the Netherlands, current policy fails to address these uncertain risks because risk classification is determined process‐wise (i.e., genetically modified organism [GMO] and non‐GMO), there is a strong focus on quantifiable risks, and the linearity within current governance (science–policy–society) hinders iterative communication between stakeholders, leaving limited room to anticipate uncertainties at an early stage of development. A suggested concept to overcome these shortcomings is the Safe‐by‐Design (SbD) approach, which, theoretically, allows stakeholders to iteratively incorporate safety measures throughout a technology's development process, creating a dynamic environment for the anticipation of uncertain risks. Although this concept originates from chemical engineering and is already widely applied in nanotechnology, for the field of biotechnology, there is no agreed upon definition yet. To explore the possibilities of SbD for future governance of biotechnology, we should gain insight in how various stakeholders perceive notions of risk, safety, and inherent safety, and what this implies for the applicability of SbD for risk governance concerning industrial biotechnology. Our empirical research reveals three main themes: (1) diverging expectations with regard to safety and risks, and to establish an acceptable level of risk; (2) different applications of SbD and inherent safety, namely, product‐ and process‐wise; and (3) unclarity in allocating responsibilities to stakeholders in the development process of a biotechnology and within society. ... Read more

Dit verslag geeft de bevindingen weer van een kortlopend onderzoek naar het gebruik van waterstofcyanide (HCN), ook wel Blauwzuur genaamd, in het veld van de (bio)chemie. In dit verslag worden de toxische eigenschappen van deze chemische stof afgewogen tegen veiligheidsaspecten vanuit het kader van Safe-by-Design gebruik makende van Inherent Safety Principles (ISPs). ... Read more