Program

Rare Diseases Community

Simona Bellagambi, EURORDIS - Rare Diseases Europe, IT

EURORDIS - Rare Diseases Europe is a unique, non-profit alliance of over 1,000 rare disease patient organisations from 74 countries that work together to improve the lives of over 300 million people living with a rare disease globally.
Each rare disease affects a small number of patients in each country but, when considered all together, the over 6000 rare diseases are affecting a minimum of 4% of the population in each country, that means 300 million people worldwide and over 30 million people in Europe, as well as their families and caregivers.
72% of RD are of genetic origin
75 % affect children
70% have their onset during childhood
Close to 5 years is the average time to get a diagnosis
Since most rare diseases are chronic, progressive, degenerative, disabling and frequently life-threatening, they have a profound impact on the daily lives of people with a rare condition and their families. Many people affected live in the margins of society, often undiagnosed, unrecognized, and unable to access services available to common conditions. These factors impact family finances and mental health, and are detrimental to their active participation in society. As such, people living with a rare disease constitute a vulnerable and neglected population, mostly invisible to the system.
On the 16th of December, 2021, the United Nations General Assembly adopted the first-ever Resolution on ‘Addressing the challenges of persons living with a rare disease and their families”. This important milestone represents the recognition and a formal commitment of the 193 UN Member States to support rare disease policies to promote and protect the rights of everyone living with a rare disease and their families.
Despite the improvements achieved over the last years, the rare disease community still has vast unmet needs:
Accurate and timely diagnosis is critical to end the diagnostic odyssey experienced by PLWRD and ensure their access to appropriate health and social care but currently the average total diagnosis time is close to 5 years and 60% are misdiagnosed or not taken seriously, many remain undiagnosed.
Access to treatments and therapies was identified as the top priority for people living with a rare disease by 2030. Only 6% of all known rare diseases have an approved treatment option, and 69% of rare disease patients have received only symptomatic treatment for their rare condition, whilst unacceptable inequities between countries on time to accessibility of treatment still persist.
Rare conditions impact the mental health and wellbeing of not only the affected individual but also their support network (family and friends). As said, the majority of rare conditions present in childhood and the impact on the mental health of these children as well as their siblings and parents can be severe. The population of people living with a rare disease (PLWRD) in the EU are in a vulnerable situation due to the accumulated impact of multiple intersectional needs – such as living with a complex condition with multiple comorbidities, living with a visible or invisible disability, being a child or adolescent, facing financial hardship, or living with stigma and discrimination.
People living with rare diseases often also have specific care and independent living needs due to the very nature of their disease. They often must go through long, complex and fragmented care pathways and are at risk of reduced income or unemployment, social isolation and discrimination, as the coordination of care tasks falls mostly on the family, and primarily on women.
People with rare diseases and parents of children diagnosed with rare diseases are extremely brave and are committed to living and making others live to the best of their ability, life but they certainly would have wanted a life lived fully for a long time and without suffering.
New technologies, scientific progress, bring hope, as it has happened with advanced therapies capable of changing the course of the disease and therefore allowing a "cure" which however currently only concern very few diseases and also for cancer with CAR-T or CRISPR gene editing.
Significant efforts and improvements have also been made when it comes to diagnosing rare diseases earlier mostly thanks to the development and use of genomics technology. There is significant momentum worldwide to focus efforts on prevention, more specifically secondary prevention which focuses on the early detection and prompt treatment of diseases or conditions to prevent progression and complications. This technology that will enable us to rapidly and readily expand NBS by adding dozens or a couple of hundreds serious and treatable childhood conditions to the list of these national NBS programmes.
We need to increase scientific knowledge to avoid the risks associated with these new techniques as much as possible but we must also commit ourselves to creating a public debate that will allow not only the community of people with rare diseases, but the public at large, to raise awareness and form an informed opinion on this matter and therefore an informed decision, based on the available scientific knowledge.
In conclusion, the potential of bioengineering technologies to address the vast unmet needs of the millions of people living with a rare disease is highly appealing and raise hopes of an extremely vulnerable population. However, advancing in this area cannot happen without addressing the ethical, legal and social issues that these breakthrough technologies arise. Could it make a difference, from an ethical point of view, when these technologies are used? Before or after birth?
It is crucial that people living with rare diseases, their families, patient and citizens at large are engaged as partner in an open dialogue, based on transparent information on the technologies and their benefits and risks, to take on board perspective and concerns. This will favour informed choices, wider acceptance and broader take-up of the novel technologies, in the full respect of the human rights and dignity of the individual.
Surely the main ethical problem once we get to the safe development of these technologies, would be their equal access to all those who need them.

Ethical Foundations of Emerging Technologies

Monica Consolandi, Fondazione Bruno Kessler, IT

As new technologies rapidly integrate into various aspects of our lives, including sensitive areas like healthcare, it is essential to reflect on their ethical foundations. Do emerging technologies uphold core ethical principles? Do they keep humanity at their center, and do they genuinely enhance human flourishing? These are complex, evolving questions that warrant ongoing exploration, and we look forward to engaging in this crucial discussion.

New Genes and New Humans: Making People Better or Making Better People?

Charles Davis, St. John's Medical College, IN

Genetic engineering and germline interventions which result in genetic alterations are direct attacks on humanity, for the human genome is the heritage of humanity. Mixing human genes with animals to create chimeras is the worst form of biotechnology that leads to unpredictable and uncontrollable results endangering the human species itself. New genetic designs and all forms of human enhancements pose a challenge to the identity, integrity and dignity of existing individuals as well as of the entire humanity including future generations. Should we improve human nature, are we allowed to do what we can do and how are the potential consequences to be assessed? Whereas a therapy may be ethically justified even if it involves invasive interventions at human nature, enhancements are rejected by many religions because they imply a refusal to accept the natural qualities of the humankind and attempt to create new types of natures which could be established as non-humans. Genetic technologies may have positive elements to combat hereditary diseases and prolong life through transplantation of organs and protheses, but they should not degenerate humans and abandon the idea of humanity. Religions speak of inalienable natural human dignity, which makes humans equal and equals. Genetic modifications may harm the values of human dignity, justice, equality and solidarity. The nature-given human dignity should be made unavailable for any manipulation and humans should not be reduced to objects. The inviolable bioethical principle of human dignity plays a vital role in stopping manipulative human experiments. Humans should not play God but be humble stewards.

New Genes and New Humans: Making People Better or Making Better People?

Roberto Dell'Oro, Loyola Marymount University, USA

In my paper, I offer a philosophical critique of prevailing bioethical discourse on human genome editing. I speak about the limits of such an approach and the need for a broader integration of perspectives. Mine is a critique of the “principle-based” approach, as we all know, the dominant methodology framing not only the general features of bioethics, especially American bioethics, but also the many areas of public ethical engagement, including the area of human genome editing. To begin, public argumentation rests on specific limitations imposed on both complex conceptual premises and semantic sophistication. The result is a kind of imperial univocity dominating the field: it imposes a notion of ethical argumentation reduced to evidentiary plausibility, as such potentially intelligible without any deeper philosophical commitment, whether anthropological or metaphysical, let alone theological. This seems too little, not only with respect to the theoretical seriousness of public argumentation, including its requirements for a different conceptual “thickness.” Puzzling is also the inability to see the existential weight of what is at stake in the debate: not just the rightness of individual practices, judged in a piecemeal fashion, and with reference to statistical acceptability, but the good of our own lives in an integral sense.
In this light, the question is not only whether a society can feel comfortable with the introduction of practices hitherto considered unethical, or newly appearing on the moral radar thanks to new scientific and technological advances. The deeper question might be whether the practices at stake in the public debate do contribute to enhance the human quality of our deepest experiences, or compromise it forever. How do they affect our own understanding of the humanum broadly conceived, the authentic good of the human condition? For sure, one ought to distinguish between statements of public policy and broader expressions of philosophical rumination. Public policy statements, whether in the form of legally binding documents, regulatory reports, or more general recommendations, cannot fully convey the conceptual “thickness” of ethical discourse, nor should they. Public policy aims to convey the consensually defined position of specific social bodies. Its function is to offer a minimal basis for a conversation to begin, not to exhaust all the conceptual resources that might inform and define the complex matrix of philosophical premises, analytical arguments, and prudential conclusions on a specific action or practice.
Still, the tendency I see in bioethical discourse today is to collapse the potential richness of the latter into the relative “thinness” of the former. Human genome editing is a case in point. Reference to the principles of beneficence, non-maleficence (safety), autonomy, and justice, though differently orchestrated in their application, are ubiquitous in the statements of official bodies. They seem to have a prima facie validity not only in terms of their normative weight, but also with respect to a taken for granted linguistic shallowness. Thus, non-maleficence will be essentially reduced to safety, beneficence to social benefit, autonomy to “expressive individualism” (Robert Bellah), justice to fair distribution of resources, etc.
In my presentation, I point to the 2017 National Academies of Science, Engineering, and Medicine report (NASEM), which rests on such principle-based strategy. I submit that a discussion on human genome editing entails retrieving a broader horizon of meaning for our own reasoning. It might also call for a different attunement to what I refer to as the primal ethos of life. The first calls for an epistemological recharging. The second for renewed metaphysical sensibility.

Is AI Affecting User Autonomy?

Mauro Dragoni, Fondazione Bruno Kessler, IT

In human-computer interaction (HCI), understanding and encouraging user autonomy within dialogue systems is essential, especially for applications like health advisory chatbots where user control over information is critical (https://arxiv.org/html/2402.09716.pdf; https://blog.practicalethics.ox.ac.uk/2024/03/national-oxford-uehiro-prize-in-practical-ethics-undisclosed-conversational-ais-a-threat-to-users-autonomy/). Based on Webster dictionary autonomy refers to “the quality or state of being self-governing”. Savolainen&Ruckenstein (2024) divide the user autonomy of AI agents into various dimensions such as decision-making autonomy, control autonomy, transparency, responsibility, feedback mechanisms, and adaptability. In this study, we are focused on decision-making autonomy, which includes control over conversation flow, and freedom from unnecessary information.
To this end, the present study firstly tries to develop and validate a comprehensive framework to assess user autonomy within dialogue system interactions, and subsequently, it aims to create tools that help improve user control in these systems, allowing users to decide how much information they receive. A better design would answer users’ questions directly and then offer more information only if they require to. This will help build trust and satisfaction, especially when users need to make important decisions.

Soka Gakkai Buddhism and New Biotechnologies

Guido Giordano, Roma Tre University, IT

According to Buddhism Life is a continuum and birth and death are just functions of its true essence. The never-ending flow of Life is regulated by the Marvelous Law of Cause and Effect perceived as illumination by Shakyamuni (the historic Buddha, IV century b.C.) and transmitted in written form in the Lotus Sutra (I-II century a.C.). In the XIII century the Japanese monk Nichiren Daishonin, proclaimed that the invocation of the Marvelous Law of Cause and Effect by chanting Nam Myo Ho Renge Kyo (that is its translation in Chinese ideograms with a Japanese pronunciation, with the prefix Nam which means “I dedicate myself to”) is the cause able to transform any karma (or destiny) and the fundamental direction (jp. ichinen) of our heart-mind attaining illumination, because the ability to perceive the true essence of life exists in any individual life and only needs to emerge in response to that cause. The access to illumination is therefore for anyone at any time, laying the ethical foundation for the supreme respect of any individual life that Buddhism promotes.
Within this framework Buddhism welcomes any effort to protect and improve individual lives, to cure illness and diseases, including any effort to relieve unnecessary sufferance, so that scientific advancements in biomedical sciences, as in any other field of science, are supported and seen as a great manifestation of compassion.
Some of these scientific advancements, especially concerning some new biotechnologies, are today under scrutiny because they raise ethical issues and questions, for example regarding if and the extent to which the human genome could be modified. In this regard, Buddhism, while supporting and promoting the integrity of individual lives, focuses on the true and deep intentions (causes) that move science behind its realizations. To this aim, it is essential to openly and fully discuss in a multidisciplinary, multicultural, and multireligious framework to find a common, shared path along which new biotechnologies are developed as an expression of compassion, solely to protect individual lives, avoiding altering their integrity and that of future generations.
The Buddhist philosopher and peacebuilder Daisaku Ikeda (1928-2023) said “In my opinion, every available means must be used to try to mitigate the suffering. To this end, all possible efforts must be made. But [scientific advancements] must not be allowed to interfere with the intrinsic right of life to remain so.”

Life 2.0: Building a Synthetic Cell in the Lab

Kerstin Göpfrich, Max Planck Institute for Medical Research, DE

What is life? Can we synthesize it from inanimate building blocks? Long a philosophical question, the emerging field of bottom-up synthetic biology has made progress towards constructing a cell from molecular parts. Our vision is to create a simple model of a cell that consists of a lipid vesicle and operates based on our own custom-engineered and genetically encoded molecular hardware made from DNA and RNA nanotechnology. Recently, we realized mechanisms for vesicle division and build functional DNA and RNA-based mimics of cytoskeletons, capable of cargo transport and signal transduction. Ultimately, by coupling GUV division to their informational content and their function, we aim for a prototype of a synthetic cell capable of evolution. What would the synthesis of a cell mean for life as we know it? Could it revolutionize manufacturing or offer new approaches to treat disease?

Regulating Organoids Ethically

Søren Holm, University of Manchester, UK

This talk will briefly outline the current status of organoid research and then consider the ethical and regulatory issues that organoid research raises. It will initially distinguish between contentious and non-contentious organoids and then focus of three types of contentious organoids:
1.    Neural organoids
2.    Reproductive organoids
3.    Human embryo models
For each of these it will analyse the ethical and regulatory issues raised and discuss the underlying philosophical issues.

Cell and Gene Therapy, Ethics, and Society

Tim Hunt, Alliance for Regenerative Medicine, USA

This presentation will explore data related to US/EU approvals in 2024 as well as global data on the number of developers, clinical trials, and investment in the CGT field. In addition, it will explore some of the more salient ethical questions major stakeholders, including patients/patient organizations, policy leaders, regulators, payors, and bioethicists/religious leaders, ask about the field. Finally, it will speak to select efforts to globalize access of CGT and speak to the power of the patient.

The Physical Basis of Feelings

Nick Lane, University College London, UK

Recent work on general anaesthetics suggests a mechanism that involves electromagnetic (EM) fields generated by mitochondria, the powerpacks of complex cells. Mitochondria derive from free-living bacteria, and their acquisition enabled a major transition in evolution. EM fields give cells an integrated, real-time feedback on how far their metabolism (their ‘wetware’) has been perturbed from homeostasis. A feeling is an organism’s best guess (inference) as to its state in the world, given incomplete information. Some level of consciousness is a widespread if not universal property of life.

The Physical Basis of Feelings

Markus Maeurer, Champalimaud Foundation, PT

Adoptive cell therapy (ACT) is a treatment strategy in which engineered immune cells are re-infused after genetic ex vivo manipulation into a patient in order to achieve a clinically relevant, long-lasting anti-cancer directed immune response. ACT holds immense promise because it can treat cancers beyond the capacity of other therapeutic modalities (small molecules or biologics such as antibodies and anti- body-drug conjugates). The latter deploy a single or at most few target-specific functions, whereas therapeutic cells can affect complex systems within the tumor microenvironment (TME). With their ability to react dynamically and make decisions in context, cellular products go beyond the direct killing of cancer cells by producing pro-inflammatory cytokines to initiate a chain reaction that engages and coordinates the endogenous immune system. Despite the remarkable efficacy demonstrated in several hematological malignancies, current chimeric antigen receptor (CAR) T cell products have not exhibited adequate biologically and clinically relevant poly-functionality to eradicate most cancers effectively. Non-genetically modified immune cells directed against solid cancer include TIL which have been approved February 2024 for the treatment of patients with metastatic melanoma, who did not respond to checkpoint inhibitor therapy. Tumor Infiltrating Lymphocytes (TIL) therapy is a highly personalized active cell therapy (ACT), where tumor-infiltrating T-cells are removed from tumor-tissue, expanded and manipulated ex vivo to large numbers and subsequently re-infused into the patients, usually along with IL-2 delivery after lymphodepletion. Although the tumor-microenvironment is suppressive to mount an effective cellular anti-tumor directed immune responses, TIL exhibit a particularly epigenetic imprint imposed by the microenvironment which facilities to stay in the precursor T-cell compartment and effectively home into cancer lesions. The limitation of TIL therapy is certainly the overall low success rate – and complex inflammatory signatures imposed by systemic and local factors with a net-effect limiting clinically relevant anti-cancer directed immune responses. Possible solutions may include enrichment of a broad diversity of anti-cancer directed immune cells and tissue-context-dependent adaptability to guide immune effector functions of anti-cancer directed T-cells with precision, guiding them to specific temporal and spatial coordinates. This pivotal mechanism offers a potent avenue to increase cell fitness and modulate the tumor micro-environment (TME) in a secure manner. Presently, the incorporation of constitutively expressed transgenes serves as a rather rudimentary approach to reach this goal. Continuous transgenic expression of candidate genes may inadvertently lead to aberrant expression due to the absence of sophisticated regulatory domains found in corresponding endogenous genes. Consequently, transgenes may trigger unwieldy off-target effects or systemic toxicity and, in more extreme cases, even foster neoplastic transformations, particularly when involved in regulating cellular division. To surmount these challenges, the paradigm of contextual programming emerges, involving the introduction of carefully regulated exogenous transgenes or the modulation of the function of endogenous genes epigenetically. This approach holds the potential to effectively address concerns related to target specificity, TCR diversity (the anti-cancer ´reactome´) necessary to address tumor cell heterogeneity, T-cell fitness and shaping a TME allowing for biologically and clinically relevant T-cell responses. A bottleneck is certainly access to cell therapies associated with i) limited production capacity, ii) current reimbursement models and iii) strategic partnerships to move cell – based therapies into more comprehensive clinical trial settings.

The Quantum Underpinnings of Life

Johnjoe McFadden, University of Surrey, UK

Quantum mechanics is the weirdest of sciences that allows particles to inhabit multiple locations in space and time at once, travel through classically-impenetrable barriers and possess spooky connections across vast regions of space. Yet the science is usually considered to be limited to the tiniest components of matter, such as protons or atoms. As systems get bigger, classical behaviours in which particles tend to be in one place or another, cannot penetrate impenetrable barriers and are not spookily connected, tends to dominate. However, in the last several decades experimental evidence for the weird aspects of quantum mechanics has been found in a range of biological phenomena such as avian navigation, enzyme action, photosynthesis, the sense of smell and mutation. In this talk I will review recent advances in quantum biology, including from my own laboratory, as well as discuss their relevance to our understanding of the nature of life and the possible creation of synthetic life.

The Role that Research Ethics Committees Play in the Governance of Emerging Technologies

Laura Palazzani, LUMSA, IT

The role that research committees could and should play in these areas is a matter of debate. While several initiatives have proposed ethical review/evaluation models for other research areas, and some institutions have created research ethics committees for emerging technologies or expanded the scope of existing ethics committees to include emerging technologies, efforts to adapt ethical review to new and emerging technological research remain heterogeneous and problematic. There are challenges to be discussed, in order to identify the specific role of ethics committees for research in the area of emerging technologies.

Harnessing the CRISPR Toolbox to Engineering Biology

Randall Platt, ETH Zurich, CH

Molecular technologies enabling the high throughput interrogation of genetic elements fuels our capacity to understand and control complex biological systems. With current methodologies used in the field of biomedicine the rate at which genes are being associated with biological and disease processes has drastically outstripped the pace at which their causality can be tested and understood. There is also a treasure trove of biological information that is lost or hidden from us when using conventional snapshot experiments. In this lecture you will hear about how we are harnessing the CRISPR toolbox to engineer biology and overcome these challenges, specifically through developing tools and methods for in vivo CRISPR screens and engineered cells that record their own gene expression.

New Technologies: Revolutionizing Health, Challenging Governance

Andreas Reis, World Health Organization, CH

Clinical care, public health, and health research are being revolutionized by new technologies such as Artificial Intelligence (AI) and genome editing, and neurotechnologies. With the support of AI techniques, patterns in complex genomic datasets can be identified, facilitating the discovery of gene functions, regulatory elements, and variations linked to diseases. AI-driven approaches are also pivotal in personalized medicine, where they aid in the development of tailored therapies based on individual genetic makeup. Additionally, AI-driven tools are instrumental in accelerating drug discovery by identifying potential therapeutic targets and streamlining clinical trials.
While these advances can lead to enormous benefits for human health, ethical challenges and human rights concerns remain, including equitable access to these technologies, data privacy concerns, and the need for explainability of AI models. For oversight and governance at an institutional level, clinical and research ethics committees could play an important role. At international and national levels, various initiatives for promoting governance are underway, e.g. by the United Nations, the European Union, or by national bioethics committees. But these efforts are complicated by the unprecedented speed of development, the power of technology companies, and the current international context.

Social Responsibility of Medical Information and Its Perception

Luigi Ripamonti, Corriere della Sera, IT

Today, medical-scientific information holds an increasingly important social role. One reason for this is the constantly growing expectations fueled by the asymptotic progress of science, particularly in the medical field. These expectations, in turn, drive the production of news aimed at satisfying them, often resorting to hyperbole that can, at best, create false hopes and, at worst, promote genuinely dangerous recommendations, as witnessed during the Covid-19 pandemic. In this context, developing a strong sense of responsibility among those who produce and disseminate information on these topics becomes even more crucial than in the past.

The Places of Governance in Synthetic Biology

Robert Smith, University of Edinburgh, UK

What is a place for governance? In the life sciences, we might think of the ethics committee as the obvious one. If you working with genetically modified organisms, perhaps it's the biosafety committee. In synthetic biology, which I have been studying for nearly a decade, perhaps the most infamous place is the 1975 Asilomar Meeting, in which scientists assembled to discuss how to move beyond a self-imposed moratoria on recombinant DNA research. In this talk, I want to introduce you to several sites of governance that seem to replay memories of this meeting and point out how they are limited in their own particular ways -- the people in the room, the conversations that are had and, for the most part, their tenuous connections to decision making. In so doing, I want to ask whether thinking with ideas of 'place-making' might help us to create new spaces that allow people to gather to discuss developments in the life sciences in ways that do not merely replay the memories of the past.

A New Skin: Self-Synthesizing Artificial Cells via Enzymatic Polymerization

Andrea Belluati, TU Darmstadt, DE

Artificial cells, serving as biomimetic microstructures, emulate the functionalities of natural cells, becoming building blocks in molecular systems engineering and serving as vessels for synthetic biology. We unveil the creation of polymer-based artificial cells, synthesized enzymatically, with a capability for protein expression. The construction of artificial cells was accomplished utilizing biocatalytic atom transfer radical polymerization-induced self-assembly (bioPISA). To this end, myoglobin facilitates the synthesis of amphiphilic block copolymers, which self-organize into various structures including micelles, worm-like micelles, polymersomes, and giant unilamellar vesicles (GUVs). Throughout the polymerization process, the GUVs encapsulate diverse cargo, such as enzymes, nanoparticles, microparticles, plasmids, and even cell lysate. Consequently, the formulated artificial cells function as microreactors, facilitating enzymatic reactions and osteoblast-inspired biomineralization. In addition, when supplied with amino acids, they are able to express proteins, thus emulating prokaryotes, as they constitute a microscopic reaction compartment that holds genetic information, and allows gene expression. Finally, artificial cells can be further equipped with internal compartments in sequential reactions, imitating the eukaryotic cell subdivisions.

Empowering Ethical LLMs Interaction for End Users: Scoping Review of Available Models and Tools Adaptation

Gianmarco Di Palma, Italian Society of Artificial Intelligence in Medicine, IT

The rapid advancement of artificial intelligence (AI) technologies, especially large language models (LLMs), necessitates the development of robust ethical frameworks to mitigate potential risks to public health and safety. While tools like ALTAI exist to support the ethical development of AI systems by integrating ethical principles into the development lifecycle, a critical gap remains in empowering end users to engage with AI technologies responsibly. This study addresses aims to address this gap by conducting a comprehensive, multi-phase investigation to retrieve tools for ethical use of AI and LLMs by end-users and to adapt validated tools or scales if none are present. A comprehensive search of major scientific literature databases such as PubMed, Scopus, Google Scholar, along with grey literature, will be performed. An evidence synthesis of the findings will be performed. An iterative consensus-building process such as the Delphi method will be used by a multidisciplinary team of experts to evaluate the retrieved tools and determine how to better adapt them for end-users. A pilot testing phase will be carried out to ensure methodological appropriateness of modified tools. Copyright and intellectual property rights will be fully addressed. By integrating ethical considerations throughout the development process using tools, the study aims to reduce bias and enhance transparency in AI decision-making. The retrieved or adapted tools will empower end users to identify and address ethical concerns during their interactions with AI. This will contribute to increased public awareness and understanding of AI ethics.

Prioritizing Healthcare AI-driven Innovations: Key Insights and Strategic Interventions Focusing on Ethical Challenges

Diana Ferro, Bambino Gesù Children Hospital, IT

Introduction: The integration of artificial intelligence (AI) in biomedicine presents significant ethical challenges that require interdisciplinary collaboration to address. The Biomedical Data Science Innovation Lab (BDSIL) workshop focused on the ethical challenges of AI in biomedicine convened experts from diverse fields to identify and prioritize these challenges through a "Wouldn't It Be Great If" (WIBGI) activity.
Methods: Experts from diverse fields, including mathematics, statistics, basic science, clinical biomedicine, and ethics were divided in multidisciplinary mixed group and asked to brainstorm ideas based on their experience with Real World clinical implementation of AI driven medical interventions and tools. 78 WIBGIs were collected and analyzed using Large Language Models to identify key themes requiring immediate attention.
Results: The analysis revealed four major themes:
1. AI/ML Methods: Challenges and opportunities in the application and enhancement of AI and machine learning in biomedicine.
2. Patient Perception of AI: The need to develop strategies to enhance patient understanding, acceptance, and engagement with AI in healthcare.
3. Model Evaluation Strategies: The ongoing challenge of assessing and improving the performance and reliability of AI models in healthcare settings.
4. Data-Related Issues: The fundamental importance of data quality, management, and integration to support advancements in AI and model evaluation.
To address the ethical challenges of AI in biomedicine, participants recommended a multi-faceted approach:
1. Enhance AI/ML literacy: Conduct workshops and training programs to improve understanding of AI/ML technologies and their limitations among researchers, clinicians, and policymakers.
2. Empower patients: Develop patient-centric programs that foster trust, encourage active participation in decision-making, and address concerns related to privacy and data sharing.
3. Prioritize model evaluation: Establish rigorous processes for evaluating and validating AI models, ensuring transparency and reproducibility.
4. Invest in infrastructure: Allocate resources to build robust data infrastructure, ensuring data quality, interoperability, and accessibility while safeguarding patient privacy.
Conclusion: This finding provides a roadmap for prioritizing critical areas of focus in the ethical implementation of AI in biomedicine. By implementing these strategic actions, stakeholders can work together to maximize the benefits of AI in biomedicine while mitigating potential risks and ensuring ethical, equitable, and patient-centred care.

Role of Surface Phase Transitions in Biology

Samuel Santhosh Gomez, University of Augsburg, DE

'Engineering Life' and research that surrounds this topic, sits at a unique position in the field of natural sciences, where an inter-disciplinary approach is needed not only to understand and develop the science for engineering life (or understanding "What is life?" more generally) but also to understand the ethical implications of such a research question.
As a theoretical physicist, our role in this research question comes with proposing models that have the predictive power to answer the potential implications that experimentalists will need to face as they get closer to engineering a life like system.
Our group works with researching physical phenomena that we believe will help provide useful insight in understanding the theory of like-like systems, at different scales. The project I will present is a project that describes a macro-scale process of epithelial cellular organisation, through the formation of the tight-junction complex. However, to properly understand cellular organisation at this scale, there are processes at the micro-scale that include intra-extra cellular communication through cellular receptors. We are hoping to shed some light on this process of how cells can communicate from the interior to the exterior of cells, and the role that phase separation on membranes (and surfaces) have on this process. As theoretical physicists working on this topic our aim in the conference is to share ways in which we study and approach the topic but would like to exchange knowledge and information for valuable feedback with other experts that look at the consequences of this research topic from different points of view.

Theory of RNA Replication and Evolution in Phase-Separated Systems

Gaetano Granatelli, University of Augsburg, DE

The engineering of living systems or specific life-like processes, and the ethical issues that stem from it, require unified approaches which transcend the boundaries of individual disciplines, entailing insights from diverse fields to understand their full implications and devise effective solutions. Ethical questions always lie upstream experimental realisations, and the predictive scheme of theoretical biophysics embodies the potential to trigger ethic discussions in its ability to extract general principles that are relevant in the context of De Novo Life development.
We aim to develop a theoretical framework that can account for RNA replication and evolution in phase-separated systems. It is known that evolution is due to the error-prone replication processes of genetic material performed by replication machinery translated from the same genetic material. Even if the understanding of how the complexity of primitive self-replication molecules develops through Darwinian evolution still remains a mystery with regards to the origin of life, the ability to evolve is thought to be a key feature which distinguishes living things from non-living molecules. Specifically, in our project we want to investigate how liquid droplet-like compartments could play a role in providing spatially confined micro-environments which allow for the coevolution of RNA replicators together parasitic RNAs. This coexistence could create a robust RNA replication network which might have the chance to evolve into the complex replication machinery of cells. As theoretical physicists, our role in this research question would provide quantitative tools which could possibly guide experimentalists in the design of self-replicating, life-like systems.

The Ethics of Engineering Life: Individualist vs Collectivist Approaches

Tess Johnson, University of Oxford, UK

The question of whether we should engineer life is often framed as one that parents can make, in isolation. Should prospective parents in a more technologically advanced future scenario pursue, say, germline genome editing to genetically enhance a future child? I argue against this approach, by focusing on decisions surrounding whether we should engineer life as a community, collective endeavour. We ought not consider only the interests and concerns of parents and the future child, but rather the whole society in which future genetically enhanced people would live. However, existing collectivist arguments in the genetic engineering literature tend to take an approach that already assumes the negative normative valence of genetic enhancement of future people, often leading to a prohibitive stance without adequate ethical analysis. I argue this is due to two common problems with collectivist arguments: first, inappropriate acceptance of individualist assumptions, and second, failure to appropriately weigh individual vs collective ethical considerations. I conclude by indicating that to further develop a collectivist ethical analysis of whether we should genetically engineer future lives, I suggest we may look to collectivism in public health ethics for guidance.

Building Biomimetic Hardware for Synthetic Cells

Erik Poppleton, Max Planck Institute for Medical Research, DE

Biology is made up of a wonderful and diverse set of molecular interactions which give rise to higher-order structure and function. One of the fundamental capabilities of living systems is homeostasis, maintaining the internal chemical environment permissive to cellular function. Core to this capability are compartmentalization with membranes and chemistry-selective permiabilization of the membranes with pores. Here, we present the development of membrane nanopores composed entirely of RNA. By working with functional RNA components, we 'short circuit the Central Dogma', allowing direct coupling between genotype and phenotype, and expand the toolbox available for engineering life. With these unprecedented opportunities to engineer biomimetic hardware, the immediate question arises how far engineering life can and should be taken, and how we should structure our research to take externalities into account.

Using Animal Models to Enhance the Welfare of Future Animal Models

Mattia Pozzebon, University of Trieste, IT

When discussing animal models, we refer to non-human species employed in biomedical research as they can replicate certain aspects of a biological process or disease observed in humans (Ostrander, 2023). The use of animals in biomedical research has undoubtedly led to significant advances in understanding human disease. However, it is important to acknowledge that the use of animals in research has raised concerns about their potential exploitation and suffering. The bioethics debate has focused on the potential use of gene-editing techniques, such as CRISPR-Cas9, to promote animal welfare. One widely debated approach involves creating disenhanced animals with diminished susceptibility to suffering (Thompson, 2008; Shriver, 2009; Shriver & McConnachie, 2019; Devolder & Eggel, 2019). Obtaining animals that have been disenhanced is currently genetically impractical, and further research is required. Animal models play a crucial role in gaining a better understanding of the biological processes involved in disenhancement. We are presented with a paradoxical scenario where potentially suffering animals are used to obtain animals with reduced suffering capabilities for future use as animal models. Hence, it is important to carefully evaluate the ethical implications of subjecting animal models to suffering for the sole purpose of enhancing the welfare of future generations of models. This issue is closely related to the debate on intergenerational ethics, which examines whether present generations bear moral responsibilities towards future generations (Narveson, 1967; Hubin, 1976; Gosseries, 2001; Gosseries & Meyer, 2009; Brandstedt, 2015).

Playing God or Playing Good? Moving from an Engineering Paradigm to a Designer's Posture Toward Life

Tommaso Ropelato, University of Turin, CH

In the ethical debate over repro-genetic and synthetic biology the formula 'playing God' is widely used to attack this new branch of biotechnologies. The argument hints at a will to create ex-nihilo, a Promethean aspiration for the creation of man by man. For this reason, 'playing God' is often taken to indicate how certain applications of these technologies to life would lead the latter to artificial and no longer 'natural' forms.
My contribution aims to shift the narrative away from this critique by proposing a move from an engineering paradigm — which, as Bruno Latour notes, focuses on 'creating from scratch' — to a designer paradigm. This posture emphasizes modesty, care, precaution, skill, meaning, attention to detail, and careful preservation. These principles guide us to reframe the question (and, why not, the title of the conference itself!): can we strive not to play the role of God, but rather that of good life designers?
Specifically, in the wake of the 'design turn in applied ethics', my work explores whether the 'Value Sensitive Design' (VSD) framework can be applied to gene editing and synthetic biology, and if so, how. Such a perspective would suggest an approach that could help us responsibly navigate the societal and ethical challenges posed by these emerging and disruptive 'life technologies'.

Record-seq

Florian Schmidt, ETH Zurich, CH

Step into the mesmerizing world of your gut's secret diaries—picture tiny bacteria penning their own autobiographies of life inside you! We will delve into a groundbreaking technology called Record-seq. Think of it as giving your gut microbiome the ability to jot down their experiences, creating a unique record of how they react to your diet and well-being. This captivating method, powered by CRISPR spacer acquisition, unveils the tales of these microbial 'authors,' chronicling their interactions and responses within your gut. Experience the wonder of how this 'microbial storytelling' can potentially transform our understanding of health and vitality. It's an adventure into the unseen, offering new insights into the fascinating link between synthetic biology and your gut!

The Quest to AI Fairness: Ethical, Legal and Technical Solutions

Yasaman Yousefi, University of Bologna, IT

In our rapidly evolving technological landscape, ethical and legal concerns have surged to prominence due to the pervasive presence of automation. The fundamental question of the fairness and reliability of automated decisions across diverse contexts has become paramount. This dissertation delves deep into the intricate interplay between fairness, non-discrimination, and the utilization of algorithms in critical decision-making processes.
My doctoral research investigates the function of algorithms and the risks associated with algorithmic differentiation and discrimination. It discusses the concepts of bias, inequality, data, historical disadvantages, equality, and non-discrimination. It also explores the role of human decisions on algorithmic discrimination and the legal and ethical significance of these decisions.
It further navigates through the legal landscape of fairness and algorithmic egalitarian harm. It dissects the models of equality, distinguishing between formal and substantive approaches. It also covers the concepts of equality and non-discrimination in the European Convention of Human Rights and the European Union, providing a comprehensive overview of the legal protections in place.
The research aims to achieve two key outcomes. Firstly, it will provide interpretative guidance for the forthcoming EU regulation on Artificial Intelligence (AI Act), expected in early 2024, from a legal and ethical standpoint. Secondly, it will develop a bias assessment tool from a technical standpoint, enabling the identification and mitigation of biases in AI systems. For that, the dissertation transitions from theoretical concepts to practical applications. It discusses the hypothesis of fairness by design, reviews the literature on existing fairness tools and checklists, and introduces a novel checklist designed to ensure fairness in algorithmic decisions.
Overall, this interdisciplinary approach seeks to harmonize diverse perspectives on fairness in AI systems, resulting in actionable solutions that seamlessly integrate legal fairness principles with cutting-edge technology and ethical considerations.
The dissertation aims at providing a comprehensive study that intertwines the technical, ethical, and legal aspects of algorithmic decisions.
In ICEEL, I will present a relevant case-study that raises questions regarding algorithmic fairness in healthcare AI. I will delve into the European regulatory landscape, as well as bioethical principles that should be considered throughout the life-cycle of and AI system.

09:00 - 09:30	OpeningRenzo Pegoraro, Pontifical Academy for Life, VA Welcome Vincenzo Paglia, Pontifical Academy for Life, VA Welcome Note Ralf Stutzki, NCCR MSE, CH Ethics and Engineering Life, Introduction and Overview
09:30 - 10:15	KeynoteRandall Platt, ETH Zurich, CH Abstract Harnessing the CRISPR Toolbox to Engineering Biology
10:15 - 10:45	Coffee break
10:45 - 12:00	Panel 1: Life moderator: Kevin FitzGerald Nick Lane, University College London, UK Abstract Sigrid Müller, University of Vienna, AT Johnjoe McFadden, University of Surrey, UK Abstract
12:00 - 12:20	Flash Talks moderator: Maurizio Muraca Gaetano Granatelli, University of Augsburg, DE Abstract Theory of RNA Replication and Evolution in Phase-Separated Systems Erik Poppleton, Max Planck Institute for Medical Research, DE Abstract Building Biomimetic Hardware for Synthetic Cells
12:20 - 13:30	Lunch
13:30 - 14:45	Panel 2: Responsibility moderator: Sigrid MüllerRoberto Dell'Oro, Loyola Marymount University, USA Abstract Mylene Botbol-Baum, UCLouvain, BE Markus Maeurer, Champalimaud Foundation, PT Abstract
14:45 - 15:15	Flash Talks moderator: Maurizio Muraca Andrea Belluati, TU Darmstadt, DE Abstract A New Skin: Self-Synthesizing Artificial Cells via Enzymatic Polymerization Samuel Santhosh Gomez, University of Augsburg, DE Abstract Role of Surface Phase Transitions in Biology Florian Schmidt, ETH Zurich, CH Abstract Record-seq
15:15 - 15:45	Coffee break
15:45 - 17:00	Panel 3: Governance moderator: Federico de MontalvoRobert Smith, University of Edinburgh, UK Abstract Laura Palazzani, LUMSA, IT Abstract Andreas Reis, World Health Organization, CH Abstract

09:15 - 10:00	KeynoteSøren Holm, University of Manchester, UK Abstract Regulating Organoids Ethically
10:00 - 10:30	Coffee break
10:30 - 12:00	Panel 4: Religions moderator: Renzo PegoraroCharles Davis, St. John's Medical College, IN Abstract Andrea Genazzani, University of Pisa, IT Guido Giordano, Roma Tre University, IT Abstract Mustafa Rashed Qaddourah, Pediatrician, Rome, IT
12:00 - 12:30	Flash Talks moderator: Carlo Casalone Tess Johnson, University of Oxford, UK Abstract The Ethics of Engineering Life: Individualist vs Collectivist Approaches Mattia Pozzebon, University of Trieste, IT Abstract Using Animal Models to Enhance the Welfare of Future Animal Models Tommaso Ropelato, University of Turin, CH Abstract Playing God or Playing Good? Moving from an Engineering Paradigm to a Designer's Posture Toward Life
12:30 - 13:45	Lunch
13:45 - 15:15	Panel 5: Medicine & Society moderator: Alberto TozziSai Reddy, ETH Zurich, CH Simona Bellagambi, EURORDIS - Rare Diseases Europe, IT Abstract Luigi Ripamonti, Corriere della Sera, IT Abstract Tim Hunt, Alliance for Regenerative Medicine, USA Abstract
15:15 - 15:45	Flash Talks moderator: Diego Puricelli Gianmarco Di Palma, Italian Society of Artificial Intelligence in Medicine, IT Abstract Empowering Ethical LLMs Interaction for End Users: Scoping Review of Available Models and Tools Adaptation Diana Ferro, Bambino Gesù Children Hospital, IT Abstract Prioritizing Healthcare AI-Driven Innovations: Key Insights and Strategic Interventions Focusing on Ethical Challenges Yasaman Yousefi, University of Bologna, IT Abstract The Quest to AI Fairness: Ethical, Legal and Technical Solutions
15:45 - 16:15	Coffee break
16:15 - 17:30	Panel 6: Artificial Intelligence / Artificial Life moderator: Ralf StutzkiMonica Consolandi, Fondazione Bruno Kessler, IT Abstract Kerstin Göpfrich, Max Planck Institute for Medical Research, DE Abstract Mauro Dragoni, Fondazione Bruno Kessler, IT Abstract

Submitting

ICEEL

Mon, 18 November 2024 (all times are CET)

Tue, 19 November 2024 (all times are CET)