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Contemporary work on the origin of life
Proceedings from Montebello Round Table Discussion airways; and consciousness. Finally, I will briefly discuss the relation of network failure and death. doi:10.1016/j.jcrc.2011.02.016
Contemporary work on the origin of life Stuart Kauffman College of Medicine, University of Vermont School of Medicine, VT, USA
In this short talk, I will review about 50 years' history of work on the origin of life, experimental and theoretical. I will discuss the famous Miller Urey experiments that fostered prebiotic chemistry; debates about the extraterrestrial and terrestrial origins of organic compounds; Leslie Orgel's heroic efforts, unsuccessful, to obtain a single-stranded RNA that template replicated with free nucleotides but no enzymes; the onset of the RNA world view, perhaps now fading; work on self-reproducing liposomes; chemical network catalysis; and my own and now others' works on collectively autocatalytic sets, realized experimentally and theoretically as a “complexity” phase transition in complex reaction networks. In addition, I will point out that real cells link exergonic and endergonic reactions and do work cycles briefly. It may be that cells and life maximizes power efficiency per unit fuel and is dynamically critical. doi:10.1016/j.jcrc.2011.02.017
Session III. Clinical Insights from Complexity Science Iatrogenesis in the intensive care unit: The interface between complex patients and simple technologies John C. Marshall St Michael's Hospital, Toronto, Ontario, Canada M5B 1W8
Critical illness is an inherently iatrogenic state. It only arises in patients who, in the absence of medical intervention, would have died to an otherwise lethal insult. Before the past century, simple interventions such as fluid resuscitation, blood transfusion, antibiotics, and surgical repair of major injuries were unavailable, and the response to infection or injury was either death or a relatively rapid recovery. The emergence of intensive care unit (ICU) technologies over the past half century added a further layer of possibility to the process of resuscitation, by sustaining life during a time of otherwise lethal vital organ insufficiency. But ICU technologies also challenged fundamental concepts regarding clinical biology and spawned an unprecedented group of new disorders. There can be no adaptive benefit to processes occurring after ICU admission because there is no evolutionary precedent, and assumptions regarding the value of trying to attain physiologic normalcy in the critically ill patient are frequently found to be flawed. Critical illness is an iatrogenic process not only because it occurs in individuals who, after the natural course of human biology, would have died but also because the interventions required to sustain life inevitably bring harm as well as benefit, and this harm becomes the fundamental phenotype of the disease state. Positive
e17 pressure ventilation delivers oxygen into the blood but at the cost of injury to the alveolar membrane, which in turn evokes a local inflammatory response and subsequent repair; in aggregate, the process is recognized as acute respiratory distress syndrome. Systemic antibiotics kill both the pathogen and elements of the host microbiota and so alter the complex homeostatic relationships that exist between the host and the endogenous microflora, alterations that result in enhanced susceptibility to nosocomial infection and other less well-characterized sequelae. Transfusion restores oxygen-carrying capacity but at the cost of a low-grade immune response to transfusion antigens and the rheologic sequelae of stored blood. Fluids sustain intravascular volume but at the cost of interstitial edema and impaired oxygen delivery at the cellular level. Yet a further, and essentially uncharacterized, level of iatrogenesis likely occurs in the critically ill. Biology is dynamic, responsive, and subject to complex variation over time. Intensive care unit technology is fixed, static, and constant. The rhythm of the mechanical ventilator remains unchanged for hours or days, states of arousal are constantly maintained using sedation scales and pharmacologic agents, and even metabolism is supported by continuous infusions of nutrients and fluids, a model that is at odds with the normal practice of mammalian feeding and drinking. One of the great challenges for complexity theorists is to aid in transforming concepts and therapeutic approaches regarding the highly unnatural state of critical illness. Normal states of health reflect the dynamic interactions of an organism with its environment. Critical illness, on the other hand, reflects the highly controlled interface of lethally deranged physiology with a panoply of functionally simple supportive interventions in a context where neither can effectively respond to the biologic nuances of the ongoing interaction. doi:10.1016/j.jcrc.2011.02.018
The patient as a complex system Andriy I. Batchinsky US Army Institute of Surgical Research, Fort Sam Houston, TX 78234, USA
Complexity science is storming into all aspects of life, and medicine is about to witness a paradigm shift in the way human physiology is understood, studied, and how illness and recovery are monitored. I will argue that the human is the quintessential complex system with all of the features and forms of complexity from the smallest composing elements to organs and organ systems manifesting self-organization and emergent properties along multiple scales. We will discuss a definition of a complex system and how it applies and translates to the human. doi:10.1016/j.jcrc.2011.02.019
Bounds in the variability of brain-coordinated activity in health and disease Jose Luis Perez-Velazquez Department of Paediatrics and Division of Critical Care Medicine, Toronto Hospital for Sick Kids, Toronto, Ontario, Canada
Contemporary work on the origin of life Stuart Kauffman College of Medicine, University of Vermont School of Medicine, VT, USA
In this short talk, I will review about 50 years' history of work on the origin of life, experimental and theoretical. I will discuss the famous Miller Urey experiments that fostered prebiotic chemistry; debates about the extraterrestrial and terrestrial origins of organic compounds; Leslie Orgel's heroic efforts, unsuccessful, to obtain a single-stranded RNA that template replicated with free nucleotides but no enzymes; the onset of the RNA world view, perhaps now fading; work on self-reproducing liposomes; chemical network catalysis; and my own and now others' works on collectively autocatalytic sets, realized experimentally and theoretically as a “complexity” phase transition in complex reaction networks. In addition, I will point out that real cells link exergonic and endergonic reactions and do work cycles briefly. It may be that cells and life maximizes power efficiency per unit fuel and is dynamically critical. doi:10.1016/j.jcrc.2011.02.017
Session III. Clinical Insights from Complexity Science Iatrogenesis in the intensive care unit: The interface between complex patients and simple technologies John C. Marshall St Michael's Hospital, Toronto, Ontario, Canada M5B 1W8
Critical illness is an inherently iatrogenic state. It only arises in patients who, in the absence of medical intervention, would have died to an otherwise lethal insult. Before the past century, simple interventions such as fluid resuscitation, blood transfusion, antibiotics, and surgical repair of major injuries were unavailable, and the response to infection or injury was either death or a relatively rapid recovery. The emergence of intensive care unit (ICU) technologies over the past half century added a further layer of possibility to the process of resuscitation, by sustaining life during a time of otherwise lethal vital organ insufficiency. But ICU technologies also challenged fundamental concepts regarding clinical biology and spawned an unprecedented group of new disorders. There can be no adaptive benefit to processes occurring after ICU admission because there is no evolutionary precedent, and assumptions regarding the value of trying to attain physiologic normalcy in the critically ill patient are frequently found to be flawed. Critical illness is an iatrogenic process not only because it occurs in individuals who, after the natural course of human biology, would have died but also because the interventions required to sustain life inevitably bring harm as well as benefit, and this harm becomes the fundamental phenotype of the disease state. Positive
e17 pressure ventilation delivers oxygen into the blood but at the cost of injury to the alveolar membrane, which in turn evokes a local inflammatory response and subsequent repair; in aggregate, the process is recognized as acute respiratory distress syndrome. Systemic antibiotics kill both the pathogen and elements of the host microbiota and so alter the complex homeostatic relationships that exist between the host and the endogenous microflora, alterations that result in enhanced susceptibility to nosocomial infection and other less well-characterized sequelae. Transfusion restores oxygen-carrying capacity but at the cost of a low-grade immune response to transfusion antigens and the rheologic sequelae of stored blood. Fluids sustain intravascular volume but at the cost of interstitial edema and impaired oxygen delivery at the cellular level. Yet a further, and essentially uncharacterized, level of iatrogenesis likely occurs in the critically ill. Biology is dynamic, responsive, and subject to complex variation over time. Intensive care unit technology is fixed, static, and constant. The rhythm of the mechanical ventilator remains unchanged for hours or days, states of arousal are constantly maintained using sedation scales and pharmacologic agents, and even metabolism is supported by continuous infusions of nutrients and fluids, a model that is at odds with the normal practice of mammalian feeding and drinking. One of the great challenges for complexity theorists is to aid in transforming concepts and therapeutic approaches regarding the highly unnatural state of critical illness. Normal states of health reflect the dynamic interactions of an organism with its environment. Critical illness, on the other hand, reflects the highly controlled interface of lethally deranged physiology with a panoply of functionally simple supportive interventions in a context where neither can effectively respond to the biologic nuances of the ongoing interaction. doi:10.1016/j.jcrc.2011.02.018
The patient as a complex system Andriy I. Batchinsky US Army Institute of Surgical Research, Fort Sam Houston, TX 78234, USA
Complexity science is storming into all aspects of life, and medicine is about to witness a paradigm shift in the way human physiology is understood, studied, and how illness and recovery are monitored. I will argue that the human is the quintessential complex system with all of the features and forms of complexity from the smallest composing elements to organs and organ systems manifesting self-organization and emergent properties along multiple scales. We will discuss a definition of a complex system and how it applies and translates to the human. doi:10.1016/j.jcrc.2011.02.019
Bounds in the variability of brain-coordinated activity in health and disease Jose Luis Perez-Velazquez Department of Paediatrics and Division of Critical Care Medicine, Toronto Hospital for Sick Kids, Toronto, Ontario, Canada