Background information concerning the topics of the Fifth Symposium of the IIfTC"Myocardial Optimisation and Efficiency and its Evolutionary Aspects"The proceedings of this meeting were published as: "Myocardial Optimization and Efficiency, Evolutionary Aspects and Philosophy of Science Considerations", edited by D. Burkhoff, J. Schaefer, K. Schaffner, D.T. Yue, Darmstadt, 1994. In the following you will find the preface. Preface This book is the result of a collaboration between scientists and philosophers. Naturally, the first question is therefore whether there is a need for philosophy of science in the daily work of scientists at all? Scientists want to know the practical use of such a discourse and to what extent philosophy of science can assist in scientific inquiries. The claim by most scientists is that animal-based physiology and research at a molecular level are necessary for practical problem solving in medicine. The origin of this conviction, which determines the direction of research today, is found in answers which stem from the 17th century, for instance, those formulated by René Descartes in his Discours de la Méthode (1637) where he writes "because if I examine these functions, which … could take place in this body, I found that these are exactly the same, which occur in ourselves, without being conscious of them … and in which, as one can see, the animals, who do not have reason, resemble us."1 If the body functions without impinging upon consciousness and resembles a machine, as Descartes writes in his "Traité de l'homme" (written 1632, published 1664), then there could not be fundamental philosophical, epistemological or moral objections against performing animal experiments.2 Since then physics and in particular mechanics have been the leading paradigm for the investigation of biological phenomena. Because this paradigm was, to a considerable degree, influenced and formulated by philosophers, one can say: "Indeed, philosophy of science has played and still is playing a definite role in the daily work of the scientist, especially in the exact sciences like physics and chemistry." Most scientists, however, many of whom are working in biology, do not realize that in doing their research they are within the philosophical paradigm of a physicalistic and mechanistic-deterministic world view. The question one may then ask is whether this physicalistic-mechanistic conception of the world is the only one which can be useful for elucidating biological and medical problems? This again is an important philosophical question, which has direct influence
on the way research is performed in the biological and medical sciences.
Because the mechanistic and deterministic view of the world has asserted
itself to a great extent in the biomedical sciences over the last century,
it might be fruitful to question this concept. The biologist Ernst Mayr
(7) does this when he asks: "Is it possible to reduce the phenomena,
laws and notions of biology successfully to those of physics?" Or
do we need another approach? Is it possible to save the unity of science
by reducing all sciences to physics? Or, perhaps, we should, as Mayr suggests,
develop a broader concept of science, which not only incorporates the
exact sciences, but also the life sciences. Ernst Mayr quotes some material
from Simpson's book (8), and adds his own similar view: "… Simpson
has clearly indicated the direction in which we have to move. I believe
that a unification of science is indeed possible if we are willing to
expand the concept of science to include the basic principles and concepts
of not only the physical but also the biological sciences. Such a new
philosophy of science will need to adopt a greatly enlarged vocabulary
- one that includes such words as biopopulation, teleonomy, and program.
It will have to abandon its loyalty to a rigid essentialism and determinism
in favor of a broader recognition of stochastic processes, a pluralism
of causes and effects, the hierarchical organization of much of nature,
the emergence of unanticipated properties at higher hierarchical levels,
and internal coherence of complex systems, and many other concepts absent
from - or at least neglected by - the classical philosophy of science."
(Mayr 1988, p. 21). We should also question the role that philosophers of science can play today to facilitate exchange with basic scientists working in biomedicine. We propose that philosophers should study and acquaint themselves with the basic and underlying concepts, notions and methods of the science with which they wish to achieve an exchange of ideas and fruitful collaboration. To do this it is necessary for philosophers of science a) to frankly communicate the foundations of their own discipline and its unsolved problems b) to "conquer" the steepness of the learning curve which allows access to the particular area of research in question, and finally c) to recognize the difficulties of understanding that the other participants in such a dialogue may have. There is yet another more general phenomenon of intellectual activity one should mention here, and that is what we might term the factor of "irritation": Only by posing new and sometimes annoying, indeed even irritating questions, can scientists become motivated to think in new ways. The same holds true for philosophers when they are forced to occupy themselves in a new way with apparently "old" questions. It would be peculiar if scientists could not deal with irritation caused by the claim of philosophers and historians of science that they should reflect on the foundations of medicine and biomedicine. If scientists accept the challenge of answering irritating questions, the way in which scientists work within their own realm is refreshed, and an additional dimension of analysis is brought to the theory of science.
The intended purpose of this meeting was to bring together philosophers of science and medicine with scientists working in the field of cardiovascular physiology to discuss the questions of optimization and efficiency in the cardiovascular system. In organizing the program, however, it became apparent that it was not easy to decide how this could best be achieved. There were differences in opinion about whether the program should be structured in a way that controversial points of view which could be anticipated should be put one against the other in order to allow for a direct confrontational approach. The alternative was to highlight the gaps in knowledge and the epistemological problems connected with them by presenting a more hierarchical outline from the so-called lower to higher levels of myocardial function and its integration into the cardiovascular system. A compromise was reached in that the program was finally structured for allowing the discussion of two main aspects: a) the concepts of optimization, maximization and economy, and b) the fundamental aspects of the controversy between assessing the energy consumed by the heart in performing work versus that consumed in producing tension. The articles are closely related to the presentations given at the conference. In the case of Hiroyuki Suga and Wolfgang Deppert, more detailed versions of the views presented were submitted incorporating and responding to aspects of the discussion that followed the talks. In addition, to attain a more complete treatment of the complex issues dealt with, experts who could not attend the meeting were invited to still express their views on various levels of optimization and efficiency in the cardiovascular system. The added contributions of H. Kammermeier (University of Aachen) and G. Heusch and J. Schipke (University of Essen and Düsseldorf) represent very valuable extensions to these proceedings. For the convenience of the readers a brief summary of the contents of this anthology is provided below: In his welcome address Thomas Kenner reminded the participants of the inspiring role of the late Kiichi Sagawa in advancing understanding of integrated cardiovascular physiology and promoting the idea of viewing such research within the broader framework of biologic phenomena. Further historical perspective is provided by noting key contributions of other cardiovascular physiologists and famous scientists in Graz. Daniel Burkhoff in his introduction gave an overview of the hierarchy of cardiac function, metabolism, and structure from the microscopic to the macroscopic level and its pertinence for understanding energy balance in the cardiovascular system. Kenneth Schaffner presented an overview of a philosophy of science approach to defining efficiency for biological systems. His contribution on philosophical aspects developed six themes which might be thought of as helpful in approaching the notion of efficiency for biological systems. He dealt with a) the importance of definitions in trying to analyze the processes of complex systems, b) stressed the advantages of a more flexible form of theory structure, and c) pointed to the looseness of the relationship between theory and experiment. In addition, d) he suggested that we may have to have many different ways in which we try to pin down our theories and that certain concepts will involve reduction and other co-evolution. He outlined e) the possibility of a fruitful way of bringing together and advancing scientific discoveries by interrelating various levels. Finally, f) Dr. Schaffner spoke of his uneasiness with conceiving evolutionary theory in terms of optimization and applying it under this conception to contemporary cardiology. Helmut Kammermeier, who was not ably to attend, contributed a chapter on the efficiency of energy conversion from metabolic substrates and oxygen to ATP. Peter Backx surveyed some aspects of myocardial efficiency as viewed from thermodynamics and statistical mechanics. In general, thermodynamic definitions of efficiency, while providing absolute measures of efficiency, do not themselves lend any insight into the underlying mechanisms of contraction. In fact, as noted by Suga (for details see contribution by H. Suga), the work done by the cardiac muscle does not correlate as well with O2 consumption (energy cost) as it does the pressure-volume-area. The understanding of the mechanism of this experimental fact represents a major challenge to various theories of contraction such as the cross-bridge theory. In general, molecular theories, such as the cross-bridge theory, must be constructed in a manner consistent with the laws of thermodynamics. This can be achieved by using the laws of statistical mechanics which also provide easily understood expressions for the efficiency of the contractile system. Norman Alpert and colleagues addressed the question of how the heart adapts to the varying demands imposed on it in daily life and under stressed conditions. The mechanics and energetics of skeletal muscle contraction were examined in muscles among different species specialized for specific tasks and in muscles within a given species that are specialized for different tasks. They suggest that the different strategies which evolved in nature to allow skeletal muscles to adapt optimally to their specific tasks are used in heart muscle as it adapts to certain stresses. The arguments presented revolve around the notion of "economy" of muscle contraction, which indicates the relation between the isometric tension-time integral and the tension-dependent heat production during a twitch. They also show how economy varies with inotropic stimulation and the type of myosin isoform present. Hiroyuki Suga spoke on the ventricular perspective of efficiency. He outlined in his lecture that there are many definitions of efficiency. Mechanical work efficiency (i.e., stroke work divided by O2 consumption) is the most popular and conventional. However, he reviewed the concept of how to quantify the total mechanical energy generated by ventricular contraction using an index called "systolic-pressure-volume area" (PVA) derived from the ventricular pressure-volume diagram. He found a linear relation between PVA and oxygen consumption under various loading conditions in a stable contractile state. The slope of the VO2-PVA relation represents the "oxygen cost of mechanical energy" and its reciprocal indicates the "contractile efficiency," i.e. the energy conversion efficiency from oxygen to PVA. This efficiency was 40% of the average and independent of various inotropic interventions. Dr. Suga also addresses the question of why one arrives at seemingly disparate physiologic conclusions when energetics are viewed in terms of "economy" and when they are viewed in terms of efficiency. Samuel Sideman in his lecture on the integrated heart: "From Micro to Macro and Back," showed that anatomical findings as well as theoretical considerations indicate that the myocardial fibers lie among minimal length geodesics of the left ventricular wall. Based upon this knowledge, he showed that the energy spent by the actively contracting fibers during systole as well as the passive fiber stress developed during diastole are minimized in comparison with any other possible fiber configuration. Subsequently, it is concluded that for a given succession of left ventricular states, fiber-shortening course and hence amount of mechanical work are uniquely determined. Kenji Sunagawa devoted his talk to the question of optimal coupling of the left ventricle with the arterial system. He suggests that in normal dogs, external work of the left ventricle is nearly maximal regardless of the level of physical activity. At the same time, metabolic energy required to generate cardiac output to meet peripheral demand was minimal. This suggests that under normal conditions not only is external work maximized but so too is efficiency. On the other hand, once the heart is unable to respond normally to the regulatory system, the optimality of ventriculo-arterial coupling would not be maintained. These unique features of ventriculo-arterial coupling are teleologically sound. However, it is still not certain whether these optimizations are "intended," in an evolutionary sense, by the cardiovascular regulatory system or a simple coincidence. Gerd Hasenfuss and colleagues devoted their contribution to the question of myocardial adaptation to stress from the viewpoint of evolution and development. They emphasized that myocardial adaptation includes reorganization of subcellular systems. As in the earlier presentation by Dr. Norman Alpert, contractile protein properties were assessed via the force-time integral of the individual cross-bridge cycle, calculated from heat and force data. Changes in the contractile protein system were demonstrated across the species and as a consequence of hemodynamic and hormonal stresses in isometrically contracting muscle strips. A close relationship was revealed between cross-bridge force-time integral and myocardial function within and across species. They suggest that this correlation implies that alterations of cross-bridge force-time integral reflect an important mechanism of subcellular adpatation to stress from a mechanical point of view. Moreover, they argue that alteration of the cross-bridge force-time integral has pronounced effects on energy consumption in the different types of myocardium. Gerd Heusch and Jochen Schipke discussed the matching between blood flow and function of a regional level under various states of perfusion. It is suggested that while the notion of a balance between global myocardial perfusion and global function is generally applicable under normal conditions, it remains unknown whether there is a precise matching of energy supply and demand on a macroscopic level. Furthermore, they point out that the traditional views pertaining to the adverse effects of ischemia are being modified by recognition of the "hibernating" state. Mark Noble and Angela Drake-Holland devoted their contribution to the question: Do the cardiac nerves optimize efficiency? They concluded that at some time in evolution, a role of the nerves in increasing myocardial metabolic efficiency is compatible with the results of experiments on chronic denervation of the dog heart. There is no information on which to base a hypothesis concerning the point in evolution at which this phenomenon developed, or which evolutionary pressures were involved. Drs. Noble and Drake-Holland assumed, from logical considerations, that if the same phenomenon is confirmed in man, it would not be due to evolutionary pressure on the human species. Rather, one might prefer to postulate that it is a phenomenon inherited from primeval ancestors. Edward Lakatta concerned himself with the question of whether myocardial adaptations may be seen as a normal consequence of aging, such that efficiency is optimized to the needs of each stage of life. All of the contributions briefly mentioned above dealt with myocardial efficiency and optimization from the viewpoint of scientists. Wolfgang Deppert in his talk and Hans Poser in his discussion remarks concentrated on notions of efficiency and energetics from the viewpoint of philosophy of science and theoretical physics and the inherent terminological and conceptual difficulties. Wolfgang Deppert especially asked the question: Is the deduction of natural laws from extremum principles compatible with the idea of evolutionary optimization? Extremum principles are criteria to uniquely determine the natural law-like behavior out of a continuum of possible sequences of events. Deppert concludes that evolutionary developments are declared as being optimal by means of an arbitrary goal-setting. Karl Acham dealt with the relationships and concepts of maximizing, satisficing and optimizing in the social sciences, outlining that it has proved useful to distinguish between the terms "effectivity" and "efficiency". This distinction is not only applicable in social sciences but is a general feature of matters regarding the rationality of means with respect to certain ends. Therefore, the distinction between the functional and the goal-oriented aspect of any activity or physiological process may be of some importance also for considerations concerning the investigation of the cardiovascular system.
Optimality models have been quite popular in the literature of evolutionary biology, but have not been extensively used in discussions of human physiology or in the other medical sciences. There does seem to be, however, a growing interest in such models in cardiovascular research. For example, a search in Medline using the terms "optimization" and "efficiency" shows that these have appeared with increasing frequency during recent years. This symposium also attests to that fact. An optimality model in evolutionary biology will identify two components: The first component is a characteristic which maximizes fitness. This may for example be prey-size and the argument is that a larger prey increases fitness because it is more energy efficient. This component identifies the design problem: How should the organism be designed in order to maximize fitness? The second component is a set of feasible solutions to the design problem. An optimality model shows that the solution realized by the organism is the one which maximizes fitness, or is optimal given the constraints of the physically feasible values (1). It is still controversial whether such optimality models should be regarded as valid scientific theories. Ken Schaffner in this volume discusses some of the reasons for this. Recent developments in cardiovascular physiology, such as the phenomena of down-regulation and hibernating myocardium, may, however, indicate that it is fruitful to pay more attention to how physiological processes contribute to optimal performance under a variety of conditions. This volume does not represent a thorough philosophical discussion of optimality models in the medical sciences. We have simply made available material which may form the basis for future discussions in the philosophy of medicine. Many of the contributions do point out a number of optimality models which could be studied by philosophers of science. Sunagawa, for example, showed that the heart is coupled to the circulatory system in such a way that the external work of the left ventricle is nearly maximum, and Sideman showed that the myocardial fiber configuration is such that the energy spent during contraction is minimized. We hope that this volume will stimulate further explorations of the role of optimality models in cardiovascular medicine.3
1 "Car examinent les fonctions … être on ce corps, j'y trouvais exactement toutes celles qui peuvent être en nous sans que nous y pensions … et qui toutes les mêmes en quoi peut dire que les animaux sans raison nous ressemblent …" (Descartes, Discours de la Méthode, 5. part., 1902, p. 46). 2 "Je suppose que le corps n'est autre chose qu'une statue ou machine de terre" (Descartes, Traité de l'homme, 1909, p. 120). But here arises a matter of interpretation. H. Poser suggests, contrary to the intrepretation by Wolfgang Deppert and Brigitte Lohff given above, that one cannot infer from Descartes' text a general permission for animal experimentation. The argumentation is more subtle because in Descartes' opinion animals do not own a soul, which is in accordance with the ecclesiastical dogma. 3 In a related approach, Elzinga and Westerhof, 1991, discuss "… the property through which the heart tends to meet the demands of the body with a minimum size during its evolution, as assumed here, appears to be inherent to the myocytes. It would be of great interest to see its genetic basis identified." (G. Elzinga, N. Westerhof 1991, p. 1499).
The preface was edited, written, compiled and corrected with the help and support of Daniel Burkhoff, New York; Wolfgang Deppert, Kiel/Hamburg; Edward Lakatta, Baltimore; Reidar K. Lie, Oslo; Brigitte Lohff, Kiel; M.I.M Noble, London; Hans Poser, Berlin; Jochen Schaefer, Bad Orb; Kenneth Schaffner, Washington; Jochen Schipke, Düsseldorf; W.A. Seed, London; Rein Vos, Groningen; David T. Yue, Baltimore, and has before going to press been subjected to the critical comments of the participants of the symposium. Acknowledgements: We thank Brigitte Schaefer who helped prepare the manuscripts for publication and Tim Schaefer for using his expert computer-technical know-how to get the manuscripts ready for print. Mr. A.C.M. Renirie, Dieren, The Netherlands, Ulrich and Raimund Freund, Reha-Kliniken Küppelsmühle Bad Orb and, especially Dr. med. Hans-Oskar Schäfer, Berlin, provided essential financial support without which it would not have been possible to organize the symposium and to finance the publication. All of them deserve special thanks. |
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