The Embassy of Switzerland in the United Kingdom invited the NCCR MSE Ethics Branch to organize a one-day symposium on "Engineering Life - State of the Art and Ethical Challenges" on Tuesday 20 June, 2023 at the Embassy in London. The aim of this extraordinary symposium was to “facilitate collaboration between the research communities in our countries in line with the Memorandum of Understanding on scientific collaboration that the British and Swiss governments signed recently.“ Leading researchers from the UK and Switzerland presented their work, encouraging a lively exchange and discourse. In addition, 8 PhD students and postdcos were invited to discuss the state of their research. An international ethics panel with experts from the Vatican, the University of Edinburgh and the NCCR MSE rounded off a symposium that facilitated personal networking and strengthened international collaboration.
Welcome to the Swiss Embassy for our evening on the ethics of Engineering Biology. Tonight’s discussion is part of a whole series of science and innovation-related events. As you may know, our governments signed an MoU on science collaboration last November and we are now involved in bringing British and Swiss stakeholders together to optimize the way in which our scientists and innovators work together.
For those of us who are not scientists, it may be difficult to understand exactly what “Engineering Biology” is, but if anyone had any doubt about what it can do for us, the development of new COVID vaccines served as a great example of its usefulness. It is therefore not surprising that the UK government lists this topic as one of their 5 priorities. In Switzerland’s bottom-up science system, we don’t really have government science priorities…. but if we did, Engineering Biology would surely be one of them as well.
About a month ago, the UK’s national “Council for Science and Technology” published a report on “Engineering Biology” with advice to the Prime Minister. The Council makes recommendation to strengthen the UK’s science and to exploit commercial opportunities. It also suggests a ‘Regulatory Observatory’, consisting of experts within existing regulators to share insights and advise both the sector and consumers.
And this brings us to tonight’s topic because as the technology develops, the questions of impact and regulation are becoming ever more important: What can be done? What should be done? What is safe and what is acceptable to citizens and consumers? This is often difficult to establish at national level, but even more so internationally - as the examples of genetically modified food or stem cell research have shown. The UK and Switzerland are both leading science nations with particular strengths in the area of Life Science Engineering. But it is also in our nature to reflect on the implications of our cutting edge research and to face the potential consequences by enacting legislation. And in Switzerland, the notion “acceptable by society” is quite literally important since issues like the regulation of research are voted on by the general public, for example in the referendum on stem cell research in 2004.
The Swiss Embassy in the UK therefore seems a fitting place to host a discussion about the state of the art and the ethics of Engineering Life Sciences. This afternoon, a scientific meeting already discussed the research going on in Switzerland and the UK. I am now looking forward to hearing more about the ethical implications from our illustrious panelist who are joining us from Switzerland, Scotland and the Holy See. I would like to thank the panelists and our partners from the Swiss competence centre “Molecular Systems Engineering” for making this event possible and thank you for taking the time to join us.
Markus Leitner
Ambassador
Embassy of Switzerland in the UK
Tuesday, 20 June 2023
13:30 - 13:35
Welcome
13:35 - 14:05
Engineering Life with Molecular Systems
Thomas Ward, NCCR MSE & Department of Chemistry, University of Basel, Basel
This presentation will summarize the efforts of the thirty groups involved in the National Center of Competence “Molecular Systems Engineering”. I will first outline the general concept of Engineering Life with Molecular Systems and go on to present recent applications of our approach to i) mimic life-like features in artificial systems, and ii) complement cellular systems with molecular or cellular prosthetics The presentation will end with the future perspectives that Molecular Systems Engineering offer to address unmet medical challenges.
14:05 - 14:35
Rapid Discovery of High-Affinity Antibodies by Deep Screening
Philipp Holliger, MRC Laboratory of Molecular Biology, Cambridge
Therapeutic antibodies have had a transformative clinical impact notably in inflammatory diseases and cancer, but their development remains time-consuming as well as costly. I will present deep screening, an ultra-high-throughput approach leveraging the Illumina HiSeq platform for massively parallel sequencing, display, and rapid antigen-binding affinity and kinetics screening at the level up to 109 individual antibody-antigen interactions. Deep screening enabled the rapid discovery of high-affinity antibodies such low-nanomolar nanobodies (VHH) from immunized-alpaca or yeast display-enriched VHH libraries and picomolar single-chain Fv (scFv) antibody leads directly from unselected, synthetic scFv repertoires in a three-day experiment. Deep screening generates large, internally-consistent genotype-phenotype (antibody-antigen binding / kinetics etc.) correlation datasets that can serve as training data for a language-model-enabled machine learning approach for the rapid in silico generation of novel scFv antibody sequences with even higher affinities. Deep screening promises to accelerate biomolecular discovery for a wide range of modalities and targets.
14:35 - 15:05
Showcase presentations
A Two-Enzyme Cascade for Precise Methylation of Small Molecules and Peptides
John Reed, Department of Chemistry, University of Basel
Artificial Vesicular Systems with Interdependent Modules
Stephan Hirschi, Department of Biochemistry, University of Oxford
From order to chaos: The act of a last resort antibiotic
Selen Manioglu, Novartis Institutes for BioMedical Research, Basel
Reprogramming the Genetic Code for Genetic Isolation
Jerome Zürcher, MRC Laboratory of Molecular Biology, Cambridge
15:05 - 15:35
Tea time
15:35 - 16:05
Principles of Synthetic Genomes Modules
Tom Ellis, Imperial College Centre for Synthetic Biology & Department of Bioengineering, Imperial College, London
The international project to construct a synthetic version of the yeast genome (Sc2.0) has been one of the highest visibility research projects in synthetic biology in the last decade. As this grand project draws to a close, Sc2.0 partners are now beginning to use the tools and knowledge of synthetic yeast genome assembly to ask new questions of yeast biology and genomics, and develop new biotechnologies. As a milestone towards custom, modular genome, we are now using synthetic genome workflows and multiplex CRISPR to examine and exploit Synthetic Genome Modules (SGMs), where sets of genes that encode a common function are relocated from their native genomic loci into new synthetic defragmented or refactored gene clusters in the chromosomes. We have used our SGM method to fine-tune pheromone sensing for biosensor systems, and are now employing it to the explore the minimal gene set for the cell cycle. In new work, we have written SGMs for aromatic amino acid biosynthesis pathways and are using these as a test bed for building new tools for inducible heterochromatin-silencing and other forms of master regulation.
16:05 - 16:35
Toward A World of ElectroGenetics
Martin Fussenegger, Department of Biosystems Science and Engineering, ETH Zurich, Zurich
With the advent of the internet of things, interconnected electronic devices are starting to dominate our daily lives and are reaching the control complexity of living systems, and yet work radically different: While human metabolism uses ion gradients across insulated membranes to simultaneously process slow analog chemical reactions and communicate information in multicellular systems via soluble or volatile molecular signals, electronic devices use multicore central processing units to control the flow of electrons through insulated metal wires with gigahertz frequency and communicate information across networks via wired or wireless connections. While analog biological systems and digital electronic devices efficiently work in their respective worlds there are no efficient interfaces between electronics and genetics. We will report our first attempts to design direct electro-genetic interfaces and our progress toward a world of ElectroGenetics and the internet of the body.
16:35 - 17:05
Showcase presentations
Engineering Chemically-Controlled Cytokine-Based Immunotherapies
Lucia Bonati, School of Engineering, EPFL, Lausanne
Engineering Synthetic Cells from Soft Matter to Life-Like Behaviours
Claudia Contini, Department of Chemistry, Imperial College, London
Regulation of Transgene Expression by the Natural Sweetener Xylose
Silvia Galvan, Department of Biosystems Science and Engineering, ETH Zurich
Noninvasive Assessment of Gut Function Using Transcriptional Recording Sentinel Cells
Florian Schmidt, Department of Biosystems Science and Engineering, ETH Zurich
17:05 - 18:00
Pub networking
18:00 - 19:00
Ethics Panel
Engineering Life sciences: do we need a paradigm change in bioethical reflection?
Renzo Pegoraro, Pontifical Academy for Life, Rome
Robert Smith, University of Edinburgh, Edinburgh
Martin Fussenegger, ETH Zurich, Zurich
Selen Manioglu, Novartis Institutes for BioMedical Research, Basel
Ralf Stutzki, NCCR MSE
Cutting-edge transdisciplinary research combining biology and engineering allows deep interventions in living organisms and will substantially impact human health and disease treatment. The lack of adequate science-communication strategies and a research pace that outruns traditional bioethical concepts warrant a new setting for moral discourse.
19:00 - 20:30
Networking + Apéro