The Dahlem Centre for Genome Research and Medical Systems Biology

  • Health

  • Australia | Germany | India | Japan | United States | Global Programs

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  • Non-governmental organization

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Executive Summary

The goal pursued in this proposal is to unlock the hidden resources of complex biology and discover better ways for curing cancer by developing AN INTEGRATIVE THEORY OF HEALTH, EcoHealth, badly needed in medicine today. The international community on Integral Biomathics comprises over 100 distinguished scientists from multiple disciplines. We collaborate on the development of novel theories underpinning biomedical research. Our focus is the investigation and application of new kinds of biology driven mathematics and computation to create innovative models and tools. These latter not only make possible the integration of information flows, they also enable us to understand the local contexts of living systems over multiple scales from cells to societies to fight diverse eco systemic ailments. Chronic (non communicable) diseases (e.g. cancer) and social diseases all share an eco systemic character and thus it is our main proposal that the methods developed in our research can be used to cure them effectively.

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The Problem

The prevailing metaphor in biology and medicine is the body as a classical machine. This approach works well for some illnesses. One sees many smiles in the recovery rooms of Cardiac centers. The situation is less upbeat in oncological wards, however. Cancer is a systemic, chronic disease - and that system does not behave mechanically. For instance, patient's reactions to immunotherapies, which have recently shown much promise, still remain poorly understood. Previous efforts to address this issue were made by Rashevsky, Rosen, Conrad, Waddington and his prominent guests of the Villa Serbelloni seminars in theoretical biology in the late 1960s. Two of them and three of their scholars are on our scientific advisory board. We believe that the most fundamental obstacle to progress has been the inadequacy of the prevailing scientific mentality, and corresponding methodology, to effectively utilize our growing knowledge. It is time to discover the living worlds with their phenomenologies, cycles, iterations, recursions, reflections, redundancies, unfoldings, vaguenesses and umwelts that could not be captured by conventional scientific models so far. Therefore we need to devise the mathematics and computation capable to describe these fundamental aspects of living systems in order to understand them. The current resources available to address the problem are constituted by the members of the INBIOSA community hosted at DCGMS, who are mainly experienced researchers in their fields. To enforce the development, integration and implementation of their ideas we need to recruit younger scientists who will complete a specialized curriculum as part of the proposal.

Proposed Solution

Our solution starts from recognizing that all the scientific knowledge that we have, however powerful, is a slim description of facts connected by theories that have the potential for immense development. In creating a context for breakthrough research it is necessary to understand how little we know and yet to give full respect to what we know so that this can be used to feel our way to new points of view and new knowledge. For this we are working on mathematical backgrounds and new grounds that provide a maximum flexibility in reworking our points of view about specific knowledge and indeed about the nature of the world as a whole. We propose, therefore, to depict the immune system and the disease or pathogen as mutually dependent hierarchical networks of {observer included} physiological processes. We further aim to develop and apply appropriate metrics that enable an investigator to pinpoint the most active and the most vulnerable pathways that may inform and improve therapies. Approaches to medicine utilizing this method already achieve notable successes in curing cases of chronic disease. To leverage and enforce these effects, groundbreaking new biomathematical and biocomputational theories supported by appropriate modeling and visualization techniques are being developed by the project partners. Deficiencies of eco systems at the organismal level manifest as diseases, but very similar types of deficiencies can be found at social or even global collective levels. Here the issues of the involvement of the participant observers is even more acute. Curing cancer may help curing social ailments.

Evidence of Effectiveness

Theoretical biology and efforts to develop mathematics and computing adequate to it have been underway since at least the 1930s and were forcefully defended at the conferences organized by C.H. Waddington (1965 1968). Progress has continued since then on a number of fronts. There is a broad consensus on the need to move from an ontology of objects and laws of motion to an ontology of relational processes characterized by partial autonomy and self organization. The validation comes from recognizing some aspects of life that previously were unintelligible and therefore ignored, e.g. epigenesis, semiosis and sentience, all of which can be seen as self regulation. The implications for health were spelt out in ecology where such thinking has proved essential for managing ecosystems without destroying them. These ideas are now being taken up in ecological economics and human ecology. The problem that we are addressing is that because interventionist forms of medicine proved so effective, the value of work in theoretical biology has not been utilized in medicine, evident in reliance on antibiotics and limited strategies of research in dealing with cancer and autoimmune diseases. Our work will make good this gap in building upon, integrating and further developing what are now well established ideas in theoretical biology (including theoretical ecology), biophysics and biomathematics, all encompassed by the INBIOSA project and our own published work in integral biomathics since 2010, and in the process, providing the means to further advance work in ecology, ecological economics and human ecology necessary for achieving ecological sustainability.

Previous Performance

The forerunner EU funded project INBIOSA began in 2011 as a follow up action of an extended survey paper (500+ references; 3 years of study) about a new biological mathematics and computation in 2010. The idea of the project was to create a community of experts from the relevant fields of research to elaborate a marching plan for developing the foundations of a biology driven mathematics and computation. Two workshops (in Paris, France and San Jose, USA) and a conference (Stirling, UK) in the course of the project helped to consolidate the diverse concepts of over 40 participants into a strategic vision defining the necessary steps required to develop an integrative model of life that overcomes the mechanistic paradigm in biology and medicine. In 2012 a White Paper authored by 17 distinguished researchers was presented to the EC along with a Springer book with 31 articles. In 2013, a special focus journal issue with Elsevier's JPBMB (5 Year Impact Factor: 3.167) presented an updated survey of the suggested direction for work and 18 original extended articles of promising research. In 2015, a second special journal issue featured 43 extended original research papers, reaching out to the fields of biosemiotics and phenomenological philosophy. A third special issue for 2017 is on the way now. Although we were initially focusing on promoting European research, our ambition to become a worldwide scientific forum has become a reality within 6 years thanks to voluntary collaboration. Therefore, we are applying for funding now to unfold the accumulated momentum.

The Team

Team Purpose

Our modern world is sick as an eco system, provoking the most apparent crisis in science now. The INBIOSA initiative began as EU funded project, a kind of 'distributed Santa Fe Institute' for theoretical studies at the edge of biology, mathematics and computation. It has developed as an international community pursuing novel approaches to scientific thinking. We try to counterbalance mainstream sciences' prevailing reductionist paradigm, which, despite its success in the 20th century, may have already passed its climax. We have the potential to overcome the problems at the root of conventional scientific thought and 'mother of all crises' - human inertness. Supported by the Dahlem Centre for Genome Research and Medical Systems Biology the novel paradigm we are developing will be crucial in defeating diseases, ranging between those that inflict the body and those that inflict society, thereby enabling global ecological health, EcoHealth, combatting the senescent condition of dissipative structures.

Team Structure

The team is organized as a hierarchical but vivid construct in terms of complementary research topics elaborated within independent, yet cooperating, working groups globally as a virtual institute progressing upon one focused subject. These groups are going to execute locally their tasks in the individual work packages identified within the overall proposal and interface globally with each other on a day to day base, while operating within relational workflows characterized by partial autonomy and self organization just as the defined topic of our research. Working groups will be led by local directors informing each other about their advancement weekly and attending face to face jour fixe meetings quarterly to coordinate their research according to the plan. The goal of this type of organization is the consolidation of research themes and projects after successful implementation and validation of their results by the local administration using quantifiable measures within larger research units to ensure the stepwise progress of the solution during the first three years of the project to form the departments of four transnational research institutes within six years. The collaboration of the individual local working groups with both local and governing control is performed on a yearly base via the research institutions they are part of.