HUMAN PRACTICES

Evolution has been a natural process for millions of years, driven by forces like competition and environmental changes. Today, with human intervention, we have the ability to guide this process through directed evolution. However, this power comes with significant responsibility. We must approach directed evolution with ethical considerations, ensuring that our advancements benefit society and do not cause harm to ecosystems or human health. PHAGEVO is an innovative project that aims to revolutionize the field of protein engineering. While our proof of concept focuses on addressing plastic pollution by enhancing a transcription factor ability to detect plastic break down products, the broader objective is to develop a versatile tool that advances fundamental technologies in protein engineering.

Our project integrates cutting-edge methods in directed evolution, artificial intelligence (AI), and environmental monitoring. We aim to create an AI-driven platform to predict and compare beneficial mutations and develop a biosensor that detects plastic degradation byproducts, enhancing pollution monitoring efforts. However, the impact of PHAGEVO extends beyond the lab. Ethical considerations and societal needs are central to our work. This section explores how PHAGEVO can influence both the world of protein engineering and sustainability, while also being shaped by global societal challenges and ethical questions.

OUR VALUES

We chose this project because we believe that providing a tool for Research & Development is one of the most effective ways to advance science, regardless of the specific field of application. By creating a versatile platform for directed evolution, we aim to empower researchers across disciplines, enabling breakthroughs in areas ranging from environmental sustainability to medicine. Our goal is to contribute to the broader scientific community by offering a resource that can drive innovation and address diverse challenges.

Throughout the development of PHAGEVO, our values as a team have been shaped by a commitment to responsibility and integrity. From the outset, it has been crucial for us to remain conscious of the ethical dimensions of our project, recognizing that scientific progress cannot exist in a vacuum, disconnected from its societal impact. This awareness was fostered through insightful conversations with researchers and experts, who challenged us to think beyond the technicalities of our work. These discussions broadened our perspective, encouraging us to reflect on everything involved in the ability to design novel proteins, from the potential risks and benefits to the long-term implications of creating entirely new biological capabilities. This helped us understand the weight of our actions and the responsibility that comes with pioneering new tools in protein engineering. By integrating these values into our project, we aim to ensure that PHAGEVO is not only a scientific innovation but also a responsible contribution to the global community.

BIOETHICS OF DIRECTED EVOLUTION

The primary goal of directed evolution, whether conducted in vitro or in vivo, is to create novel gene sequences with previously unforeseen functions. This powerful technique enables the design of new proteins and enzymes that could have a wide range of applications, from industrial processes to environmental solutions. However, as with any technology that manipulates genetic material, directed evolution comes with inherent risks. One must remain mindful of the potential for unintended consequences or even misuse of these newly evolved genes.

A critical concern surrounding directed evolution lies in its versatility: under the right selective pressures, it is possible to engineer proteins or genes for almost any desired function, regardless of their original purpose. This transformative potential underscores the need for stringent ethical guidelines and regulatory frameworks to ensure that these powerful technologies are applied responsibly and do not serve harmful purposes.

Highlighted during our fruitful interview with Dr. Manish Kushwaha, research director at MICALIS institute (joint research center of INRAE, AgroParisTech, and the University of Paris-Saclay) and co-leader of the Cellular Computing Group, other major ethical concerns arising from directed evolution are unintended bad outcomes from the evolutionary step. As an example, receptors, which are an important therapeutic target for new therapies directed toward a specific organ, tissue or pathogenic cells, may also be dangerous to evolve as they are the entry gate for viruses. The risk of evolving a protein that can enhance virus infectivity is therefore high, and strong containment measures have to be undertaken. Similarly, directed evolution on a protein that has pathogenic or toxic siblings may potentially lead to variants with such properties. Examples can be found in the literature where phage-assisted continuous evolution revealed hepatitis-C virus drug-resistance mutations [Dickinson et al., 2014]. To prevent any issues, a precise and thorough risk assessment has to precede the evolution experiment. The goal is to identify and evaluate the potential adverse impacts of evolved genes on human health, the environment, or other activities. Guidances for the risk assessment of genetically modified living organisms are available by some different governmental and international instances. These are mostly directed toward agricultural and food uses of GMOs [UNEP, 2016]) but other are more specific to genetic engineering and synthetic biology [David & Caron, 2012; Arbejdstilsynet]). Strict containment measures also prevent spreading evolved genes in the environment, which greatly reduce the risks linked to directed evolution of proteins.

To sum up, here are a few questions to answer before safely starting an in vivo directed evolution experiment:

  1. Is there a known risk with species or strains closely related to the host microorganism used for the in vivo directed evolution experiment that could lead to potentially adverse effects if released in the environment ? If any, what are these possible risks/adverse effects ?

  2. Is there a known risk associated with genes or proteins with a sequence similar to the gene or protein that will be evolved and could lead to potentially adverse effects if released in the environment ? If any, what are these possible risks/adverse effects ?

  3. Are there measures taken to reduce unnecessary mutations outside of the gene of interest that will be evolved ?

  4. Are there genetic containment measures to prevent the spreading of the evolved gene sequences outside of the laboratory ?

The host of the gene of interest in PHAGEVO is the bacteriophage M13, a non-lytic phage of the Inovirus genus that infects only bacteria. Escherichia coli on the contrary is a well known human pathogen with some strains causing severe diseases. Causing high levels of mutations on the genome of a laboratory strain can potentially lead to appearance of pathogenic traits and lead to harmful effects, primarily on the lab staff. In PHAGEVO, E. coli is a host organism for mutagenesis and selection, but no mutations are supposed to occur on its genome or plasmids. This makes PHAGEVO a safe approach for in vivo directed evolution in Escherichia coli.

As a member of the AraC/XylS protein family, composed exclusively of transcription factors, there are no known proteins with a sequence similar to XylS that have a toxic effect on their own. However, some members of this family are known virulence factors [Cortès-Avalos et al., 2021]. The transcription factor HrpX is among the closest relatives of XylS with a pathogenic effect [Cortès-Avalos et al., 2021], and is involved in Xanthomonas virulence in plants [Teper et al., 2021]. Sequence similarity search revealed that XylS and HrpX have only a 20% amino acid sequence identity. In comparison, only a few amino acid substitutions were expected during our directed evolution experiment as previously described XylS mutants (see our Part Collection page on this wiki) usually yields 2 to 5 substitutions (which is less than 2% of the whole XylS sequence). It can be considered that there is only a very limited risk linked to the possible appearance of mutants with properties similar to HrpX.

The PHAGEVO system enables targeted mutations supposed to occur on the gene of interest only. Neither the other genes on the phage, nor the genome of the bacteria. Eventually, leakiness of the terminators flanking the gene of interest or could result in a limited amount of mutations outside of the gene of interest on the phage.

Furthermore, we designed our system in order to prevent the spreading of genes into the environment. The evolved sequences are found on modified M13 Bacteriophage unable to replicate without pVI gene complementation. Therefore, the phages are ineffective outside of a bacteria strain that provides the pVI protein in trans. The containment of bacteriophage M13 also prevents contamination of other bacterial cultures in the laboratory, which can be a major concern, especially in industry. Doing a short risk assessment of the work we were planning and ensuring the containment of the genes through the design of our system enabled us to rule out major concerns about possible adverse effects of the evolved gene sequences, and safely continue our project.

To prevent the risks associated with these technologies, France and European Union have adopted legislation to regulate genetic engineering. Example of regulations on bioethic in France includes for example law n° 2004-800 of August 6, 2004 relating to bioethics, law n° 94-548 of July 1, 1994 relating to the processing of nominative data for the purpose of research in the field of health and modifying law n° 78-17 of January 6, 1978 relating to data processing, files and freedoms, law n° 94-653 of July 29, 1994 relating to the respect of the human body, act n° 94-654 of July 29, 1994 on the donation and use of elements and products of the human body, on medically assisted procreation and on prenatal diagnosis. We consulted two French Senate reports [French Senate, 2012, 2017] to better understand the legislative environment and their link to the management of risks related to genetic engineering. The main outcomes are that the potential risks linked to modification of genetic sequences and dual uses of the technology cannot be ruled out and therefore requires a particular attention in what is called a “careful vigilance”. Evaluating the benefits and risks of the technologies in a responsible way is necessary in parallel to their development to adapt legislation and take eventual measures.

At PHAGEVO, we understand the ethical ramifications of our work. We are committed to adhering to the highest standards of bioethics, carefully considering how our directed evolution tools are developed and deployed. We believe that rigorous oversight, transparency, and collaboration with regulatory bodies are essential to mitigate the risks associated with these technologies.

BIOSAFETY

PHAGEVO is an advanced technology capable of generating diverse protein variants with exceptional genetic variability. While its potential is immense, it also raises critical biosafety and biocontainment concerns, particularly for researchers, including iGEMers, who aim to fine-tune its applications. The high genetic diversity generated by PHAGEVO could inadvertently lead to proteins with toxic or harmful properties, akin to prions or other infectious agents, posing risks to human health and the environment.

These risks necessitate comprehensive biosafety measures throughout the PHAGEVO process to ensure its responsible use. It is essential to evaluate the purpose and utility of projects involving PHAGEVO by weighing the potential risks and benefits, especially when evolving proteins with high sequence homology to those found in humans, mammals, or animals. Moreover, PHAGEVO employs M13 bacteriophages, which are specific to bacterial hosts. Extending its principles to other viral systems could introduce significant safety concerns, particularly when applied to viruses closely related to those infecting humans or animals. To mitigate such risks, PHAGEVO should remain strictly confined to bacteriophages.

Another critical consideration is the potential for engineered protein variants to enhance or introduce pathogenic traits in bacterial host strains, which underscores the need for rigorous evaluation of the properties of targeted proteins. These risks highlight the importance of developing robust biocontainment strategies not only for PHAGEVO but also for other directed evolution methodologies.

A promising biocontainment approach involves incorporating non-canonical amino acids (e.g., halogenated derivatives) to engineer mutants, creating a distinct barrier between evolved proteins and natural biological systems. This strategy reduces the risk of cross-infection and mitigates unintended consequences, ensuring safer applications of this powerful technology. By integrating such measures, PHAGEVO can be harnessed responsibly to maximize its benefits while minimizing potential risks to human health and the environment.

INTELLECTUAL PROPERTY

Intellectual property (IP) refers to intangible creations of the human intellect. It is a legal right to control the application or the expression of this creation in a specific context. Through scientific research, discoveries are made and have great value to several parties for several reasons (researchers, governments, industries), IP is a way to protect their interests as well as the use of the creation. [Institute of Medicine (US) Committee on Assessing the System for Protecting Human Research Participants, 2003]

There are different ways of protecting your ideas: patents (to control the application of the idea), copyrights (to control the expression of the idea) or treating the idea as a trade secret. An IP protected by a patent can not be made, used or sold by actors other than the patent owner, and to obtain the patent, the owner must provide a full description of how the invention is made, is used and functions.

In the PHAGEVO project, the invention PACE is the IP of David Liu and his team at Harvard and is patent protected since 2012 and until 2032 [Liu et al., 2012]. In the context of the iGEM competition, which is nonprofit research, the use of patented technologies is authorized and considered as fair use. As the owners of the technologies are recognized and mentioned, the share and/or publications of our results is authorized as well. However, PHAGEVO would need an Operating license in order to be used in a commercialized product, a license without which the product could expose the selling company to legal risks such as a lawsuit for patent infringement.

This situation highlights the essential role of collaboration in research. Whether between academic institutions and industry, or between larger research units and iGEM teams, collaboration fuels innovation and drives scientific progress. While our project is an original contribution developed by our team, it has benefited from the knowledge, guidance, and shared resources of the broader scientific community. This interconnectedness is what propels research forward, reminding us that every advancement is built upon collective efforts.

ARTIFICIAL INTELLIGENCE AND THE ROLE OF DATA

Artificial intelligence plays a crucial role in the success of PHAGEVO. By utilizing AI algorithms, we are able to optimize the directed evolution process, identifying ideal protein variants more efficiently and accelerating the path to discovery. This AI tool is not only a scientific asset but also a window into the future of how biotechnology can be advanced through machine learning and computational modeling.

However, the increasing reliance on AI in science introduces its own ethical challenges. Data privacy, algorithmic transparency, and potential biases in machine learning systems must be scrutinized. The use of AI in biology requires a careful approach to ensure that these tools are designed and employed in ways that enhance research without sacrificing ethical considerations. Our interview with Dr. Alaksh Choudhury, research scientist in deep mutational scanning at CEA Genoscope, was very helpful for better understanding these challenges. First, the lack of knowledge of most users of artificial intelligence tools in science is an ethical challenge on its own as it may lead to incorrect interpretation of the results or misleading information. As scientists, it is our role to correctly interpret and share results from experiments or from artificial intelligence to keep sharing high quality data and new knowledge to the community. The critical role of data in artificial intelligence, and especially the quality of the data provided as input for the training of the artificial intelligence models, is also a challenge. Along with the quality, another ethical concern is the concentration of data in a few hands, which can pose questions related to the control and access of these data to the whole community.

At PHAGEVO, we are committed to ensuring that the AI models we develop are transparent, interpretable, and open to scrutiny by the broader scientific community.

ENVIRONMENTAL RESPONSIBILITY

Our project's commitment to combating plastic pollution highlights the importance of addressing environmental responsibility. Plastic waste is one of the most pervasive pollutants on the planet, and its degradation leads to harmful microplastics and other byproducts that contaminate ecosystems and human health.

Fethi Boughmadi, member of the iGEM Evry-Paris-Saclay 2024 team, visited a plastic recycling industry in Tunisia to better understand the problems linked to plastic pollution in this country and exchanged with the working staff and managers. The main outcome of this exchange was that plastic pollution has become a major problem in Tunisia and the Mediterranean sea, and that an effective solution is lacking. The idea of using new efficient and sustainable plastic degradation technologies based on enzymes was welcomed by the employees. The limited resources allocated for recycling around the world are a major challenge and increasing the number of solutions, such as ones based on biotechnologies and synthetic biology, can be effective only if they are cheap enough to be available for all.

Workers using a plastic grinder at the plastic recycling industry of Fouchana, Tunisia.

Through PHAGEVO, we are developing a biosensor that can detect plastic degradation byproducts, which could be pivotal for monitoring pollution levels and aiding in the development of biodegradable plastics.

The long-term environmental impact of our work is central to our mission. By promoting the development of plastic-degrading enzymes, we can potentially contribute to a future where plastic waste is more effectively managed, helping reduce its harmful effects on both the environment and biodiversity. However, this raises additional questions: How do we ensure that the plastic-degrading enzymes do not cause ecological imbalances? What happens to the byproducts of degradation, and are they truly safe for ecosystems?

These questions guide our research, driving us to ensure that the solutions we create are both effective and ecologically responsible. The PHAGEVO project takes a proactive stance in examining potential ecological impacts and designing safety measures to mitigate any negative consequences.

COLLABORATIONS

Collaboration between teams is the heart of progress, where ideas interlace like DNA strand in a whole genome, resulting in something stronger and more beautiful than any could achieve alone. It is the uniting of minds, where each person’s unique abilities are knit together, forming a fabric rich in possibilities. In this collaborative dance, challenges become lighter, solutions brighter and innovation flourishes. We move forward together, powered by the energy of unity, proving that working in harmony, our collective force can make dreams come true.

The iGEM team of Toulouse-INSA-UPS organized a mini-jamboree to give the opportunity to French, Spanish, Italian and Dutch iGEM teams to meet up during 4th and 5th of July 2024 event featuring various activities. We had the opportunity to meet Dorothy Zhang, the Vice President of Global development, iGEM Foundation and Alonso Segura Valverde, iGEM Ambassador to Latin America, as a part of the iGEM community. The event provided a unique opportunity for everyone to experience a mini jamboree, serving as a rehearsal while gaining insights from various iGEM teams as well as iGEM representatives. We all showed a genuine interest in each other's projects, engaging in meaningful discussions and offering valuable suggestions that significantly contributed to improving our ideas. Additionally, Alonso Segura delivered an inspiring speech about the iGEM community, highlighting the numerous ways we can stay involved in iGEM beyond the jamboree, even after our time as students. His insights were both enlightening and motivating, offering a broader perspective on how to continue contributing to the field.

The mini-jamboree concluded on a high note, leaving us all with a renewed sense of purpose and excitement. The event was more than just a rehearsal for the main jamboree; it was an invaluable experience that allowed each team to refine their projects while learning from one another. Beyond the technical aspects of our projects, the event reinforced the importance of collaboration, open-mindedness, and the exchange of ideas. Overall, the mini-jamboree served as a crucial reminder that iGEM is about more than individual projects, it’s about being part of a global network of changemakers dedicated to solving real-world problems through synthetic biology. This experience empowered us to push our projects further and solidified our commitment to contributing to the iGEM mission well beyond our time as competitors.

The iGEM community article about this event can be found HERE.

All the participants of the Mini Jamboree held in the UPS-INSA Toulouse campus (4th and 5th of July 2024)

The distinction of the scientific community is its worldwide aspect; indeed, it has been shaped to connect people in various ways. Using one common language, which is English, facilitates the exchange of ideas, collaboration on research, and the spreading of findings across borders. This common language allows scientists from different backgrounds to communicate efficiently, helping to spark new ideas and drive progress. Moreover, it enables the global integration of knowledge within the community making it possible for discoveries in one part of the world to quickly impact and shape the world.

The University of Evry Paris-Saclay is sharing a partnership with HUST (Huazhong University of Sciences and Technologies) leading to the creation of a joint bachelor and a joint master degree programs. During the second edition of the Chinese Summer School, organized by the University of Evry Paris-Saclay for second-year bachelor students, a scientific colloquium was held on July 12th of this year. We had the opportunity of meeting two iGEM teams from HUST, which provided a fantastic opportunity to discuss our respective projects, exchange ideas, and offer each other advice. We found out that two of our projects focused on the same topic: microplastic. Even with nearly 9000 kilometers between Paris and Wuhan, our friendship remains unshakable. Distance doesn’t change a thing, we’re like two cells sticking together."

iGEM Evry Paris-Saclay team from France (right) and iGEM HUST-UEVE-UPSaclay team from China (middle and left).

COMMUNICATION AND PUBLIC ENGAGEMENT

One of the most significant challenges for technologies like directed evolution and synthetic biology is public understanding and acceptance. Scientific advancements often provoke fear or skepticism, especially when the public perceives the risks to outweigh the benefits. At PHAGEVO, we believe that clear, honest communication is key to overcoming these barriers. As researchers, it is our responsibility to engage with the public, sharing not only the potential benefits of our work but also its limitations and risks.

Transparency is central to building trust. By openly discussing the capabilities of directed evolution, the environmental applications of our biosensor, and the role of AI in our project, we aim to demystify these technologies. It is crucial that we do not overpromise what PHAGEVO can achieve, but instead foster a realistic and informed dialogue with the public.

To this end, PHAGEVO has actively engaged with a diverse range of audiences through public talks. Our goal is to make complex scientific concepts accessible to all, ensuring that our project can be understood and supported by people from different backgrounds. This approach not only strengthens public trust but also enriches our research by encouraging feedback and fostering collaboration across disciplines.

As part of our commitment to fostering public engagement and promoting the PHAGEVO project, we delivered a series of talks and presentations at the Lebanese University and the American University of Beirut (AUB). Although our promotion at these universities was curtailed due to the unstable situation in Lebanon, we still gained valuable insights that inspired us to broaden our project’s reach throughout the communities. These sessions were designed to not only highlight the objectives and methodologies of our research but also to promote awareness of the broader implications of synthetic biology and directed evolution in addressing real-world challenges. Engaging with students and faculty allowed us to share insights into our innovative approaches to combating issues like microplastic pollution while also gathering valuable feedback and perspectives from external audiences. By creating an open forum for discussion, we aimed to demystify the complexities of our work and stimulate interest in sustainable practices among students passionate about environmental science. This initiative helped bridge the gap between academia and the public, reinforcing our belief that collaboration and transparency are essential for advancing scientific understanding and acceptance.

Summer school held by the University of Evry Paris-Saclay for HUST bachelor students.

As part of our ongoing efforts to raise awareness about microplastic pollution, our iGEM team organized an educational event from 16th to 18th of October 2024, targeted the first-year bachelor students in Life science at University of Evry Paris-Saclay. The event aimed to inform attendees about the sources and impacts of microplastics on the environment and human health. This is a special request from one of our university teacher. Indeed, the students are working on a project around the plastic topic.

During the session, we presented our project’s objectives, methodologies, and innovative solutions to combat microplastic pollution. This initiative not only educated participants but also fostered collaboration and engagement among students passionate about sustainability and environmental science.

FUTURE PROSPECTS AND GLOBAL IMPACT

PHAGEVO has the potential to significantly impact the field of directed evolution, which is widely used in biology laboratories today. One of the major challenges researchers face in such experiments is the time-consuming and costly screening process. PHAGEVO aims to overcome these limitations by streamlining the process, reducing both the time and costs required to achieve new discoveries.

As young researchers, it is important to understand how and where PHAGEVO could be used. It is also important to know the limitations and possible issues of this technology to further improve it and eventually address these limitations in the future.

First, we need to precise what is the place of PHAGEVO in the world of directed evolution. Indeed, directed evolution is a broad subject that has several subcategories. The two main subcategories are in vitro and in vivo directed evolution. The first rely on molecular biology tools only, while the second rely on living organisms. But even in this second category, there are in fact two very different kinds of technologies. Adaptive evolution relies on the natural evolution process of a microorganism under a selected pressure that can be enhanced by several means such as mutagenic chemicals or UV-light irradiation. Directed adaptation encompasses synthetic biology techniques that create variants through an in vivo mutagenesis step. PHAGEVO falls within the later category.

To better understand the needs of the academic world and private companies, we discussed with several industrials and researchers. Our participation at Toulouse Mini-Jamboree was a first opportunity to present our project and discuss with members of different companies, invited by the Toulouse-INSA-UPS iGEM team who organized this event. This enabled us to realize that directed evolution is an essential step for multiple biotech companies in the R&D process. We discussed our project more in-depth with Dr. Clément Auriol, R&D manager and project director at ADISSEO. One of the main outcomes of this exchange was that, as a continuous in vivo directed evolution system with auto-enrichment of the best variants, PHAGEVO can greatly reduce the screening requirements.

“peoples have in mind that systems for random mutagenesis + screening exist […] but know less the in vivo directed evolution systems […] that enable to get rid of high-throughput screening” Clément AURIOL said.

With the opening era of artificial intelligence, we also questioned the future of directed evolution in science and R&D in front of computer-aided protein design. All our interlocutors agreed on one conclusion: the future will be a combination of artificial intelligence and directed evolution in order to fasten the process and reduce the costs. Artificial intelligence can help to get a first set of interesting sequences, followed by directed evolution steps to improve their properties. Going back and forth from one to another could greatly help in finding optimal protein variants. Our team took into account these considerations and our final goal is to not only compare AI and directed evolution, but using the FLINT model as a basis for future directed evolution experiments with the predicted clones showing improved properties compared to XylS wild type.

We hope that the PHAGEVO technology will be used in the future to address important issues such as health or environment. Enzymes, receptors, biosensors are some of the possible objectives for the evolution of proteins and the applications are as diverse within fundamental research, health, sustainable development, cosmetology or even industry.

REFERENCES

  • Arbejdstilsynet, the Danish Working Environment Authority (WEA). Risk assessment of genetic engineering research projects, etc.
  • David C, Caron V. (2012) Les risques biologiques liés aux techniques de génie génétique en laboratoire. INRS. ED 6131
  • Cortés-Avalos D, Martínez-Pérez N, Ortiz-Moncada MA, Juárez-González A, Baños-Vargas AA, Estrada-de los Santos P, Pérez-Rueda E, Ibarra JA. (2021) An update of the unceasingly growing and diverse AraC/XylS family of transcriptional activators, FEMS Microbiol Rev 45, fuab020.
  • Teper D, Pandey SS, Wang N. (2021) The HrpG/HrpX Regulon of Xanthomonads — An insight to the complexity of regulation of virulence traits in phytopathogenic bacteria. Microorganisms 9, 187.
  • French Senate (2012) Les enjeux de la biologie de synthèse French Senate Report.
  • French Senate (2017) The genome editing revolution: the economic, environmental, health and ethical challenges of biotechnologies in the light of new research avenues French Senate Report.
  • Dickinson BC, Packer MS, Badran AH, Liu DR. (2014) A system for the continuous directed evolution of proteases rapidly reveals drug-resistance mutations. Nat Commun 5, 5352.
  • Institute of Medicine (US) Committee on Assessing the System for Protecting Human Research Participants. (2003). Responsible research: a systems approach to protecting research participants. National Academies Press (US).
  • Liu DR, Esvelt KM, Carlson JC. (2012) Method and compositions for continuous directed evolution of proteins and nucleic acids. Patent WO2012088381A2.
  • UNEP, United Nations Environment Programme (2016) Guidance on risk assessment of living modified organisms and monitoring in the context of risk assessment. Eighth meeting of the Conference of the Parties to the Convention on Biological Diversity serving as the meeting of the Parties to the Cartagena Protocol on Biosafety UNEP/CBD/BS/COP-MOP/8/8/Add.1.