I Mol Cell Cardiol 23, 403-408 (1991)
EDITORIAL What is a Paradigm
RESPONSE and When Does it Shift?
From the Cardiology Division, Department of Medicine, University of Connecticut. Farmington, CT, 06032, USA
hltroduction Drs Deppert, Lohff, and Schaefer [I] in comBiology in menting on the article “Molecular Cardiology. A Paradigmatic Shift”, [2] challenge our view that understanding of circulatory control has evolved through three paradigms, each of which was built on foundations set in place by earlier paradigms. Dr Deppert and his colleagues point out that our analysis is at variance with the views of T. S. Kuhn; [3] who stated that science advances through paradigmatic shifts in which each succeeding paradigm replaces those that had come before; according to Kuhn, science progresses through a series off revolutions, and not by the linear accumulation of knowledge. Kuhn states: “scientific revolutions are inaugurated by a growing sense, again often retricted to a narrow subdivision of the scientific community, that an existing paradigm has ceased to function adequately in the exploration of an aspect of nature to which that paradigm itself had previously led the way” [3].
What are paradigms, and how do they shift? In their thoughtful comments, Dr Deppert and his colleagues appear not to be in disagreement with our view that analyses of cardiac regulation have involved studies of the heart as an organ, of the function of individual myocardial cells, and of the variability of gene expression in the heart’s response to long-term and regional stimuli [2, q. Thus, the dispute centers on whether the systems: organ, cell, gene represent different paradigms, or whether, instead, they “belong to one and the same normal science of physiology which is dependent on the one paradigm of physics” [I]. 0022-2828/91/040403
+ 06 $03.00/O
As we emphasize later, our definition of three paradigms in cardiovascular science (organ, cell, gene) not only describes the history of scientific discovery in Cardiology during this century; in addition, our paradigms describe major shifts that took place during the evolution of cardiovascular regulation, but in the reverse order: gene, cell, organ. However, in contrast to Kuhn and his supporters, who assert that the growth of science is dismissive, our definition of a paradigm recognizes the cumulative nature of the advance of knowledge in the biological sciences [2]. This dispute could easily be resolved if the term paradigm had a clear and universally accepted meaning; it would certainly simplify this discussion if we could all agree on what we mean when we refer to paradigms and how they shift. As noted by Dr Deppert and his colleagues, however, Kuhn himself realized that this is an ambiguous term. Nor does the dictionary meaning provide much help: paradigm, which is derived from the Greek rtap& and 6Gypa (deigma (para = alongside), = sample, pattern), is most readily translated as a model, or example. How broad a model, and how inclusive an example is not implicit in this definition, so that for a given context the user is free to define the limits of this term. In seeking to resolve our dispute, therefore, we will allow Kuhn and his supporters to supply the definition; however, we do require that their definition facilitate a meaningful discussion of the history and philosophy of science. The Editorial by Dr Deppert and his colleagues discusses the meaning of Kuhn’s term, and provides a definition of a paradigm that they assert allows Kuhn’s concept of “paradigmatic shifts” to clarify the process by which knowledge of the circulation has advanced. However, as we point out in this Editorial :F 1991 Academic
Prrss Limited
A. M. Katz and L. A. Katz
404
Reply, the Kuhn/Deppert concept of paradigms, and how they shift, creates an epistemology that is of little use in describing either the development of knowledge of the cardiovascular system or the patterns by which biological regulation evolved through the sequential appearance of three distinct systems of biological control: gene, cell, orgak A definition
of a paradigm
As already noted, the dictionary definition and etymology of the term paradigm is so general as to leave us no choice but to accept the meaning provided by Kuhn’s advocates in the accompanying Editorial [I]. It was, after all, Kuhn who provided the term that we used in our earlier Editorial [Z], and Dr Deppert and his colleagues are speaking on Kuhn’s behalf. However, their definition: a “framework of the questions that are formulated within normal science, and the possible concepts that can lead to their solution”, like the dictionary meaning, is rather bland. Without further elaboration, even this redefined term cannot tell us whether our original article described “paradigmatic shifts” [Z], or simply different aspects of “one and the same normal science of physiology which is dependent on the one paradigm of physics” [I]. In the context of the present dispute, the test of their definition, and certainly its ability to help us to understand cardiovascular regulation, must be sought by examining the implications of the assertion that our three systems of regulation (organ, cell, gene) fit into a single paradigm [I]. In fact, as shown below, their definition of a paradigm so expands its meaning as to destroy its usefulness in analyzing the growth of knowledge of the heart and circulation.
Does the Kuhn/Deppert definition of a paradigm help us to understand the historical developmtnt of knowledge of biological regulation?
Dr Deppert and his colleagues assert that all in cardiovascular progress physiology described in our Editorial [Z], depending as it does on the “mother” sciences of physics and chemistry, falls within a single paradigm. Indeed, it appears that they would even include Harvey’s contribution as simply an
advance within a single paradigm, based on the principles of physics, that might even include the theories of Galen, who imagined the blood to ebb and flow, sometimes through invisible “pores” in the interventricular septum. The remarkable, indeed overreaching, inclusiveness of this definition obviates the usefulness of the concept of paradigmatic shifts in systematizing either the history or philosophy of this science. For, according to this definition, there has probably been only a single paradigm since the presocratic philosphers first postulated that natural laws, rather than whims of the gods, controlled the world around us. If, as suggested by Dr Deppert and his colleagues, all three systems of cardiovascular regulation (organ, cell, gene) are elements of a single paradigm, based on the “mother” science of physics and chemistry, then it follows that all progress in our understanding of circulatory regulation has taken place with a single normal science. One might reduce the argument of Dr Deppert and his colleagues [I] to a simple assertion: that the transition from mythical to rational explanations of nature represented the only paradigm shift in the history of science, or at least in biology. At one level, we agree with this assertion. The beginnings of Western science can be traced back over 2500 years, when Thales, Anaximander and Anaximenes in the Milesian School replaced mythological cosmogonies, such as had been described two centuries earlier by Hesiod, with a search for natural laws. As noted by Kirk and raven [7j, it was in Miletus that “the first completely rationalistic attempts to describe the world took place.“. The importance of these events, which occurred at the beginning of Classical Greek civilization, was described by Cornford: The Ionian Cities of Asia Minor were then at the height of Western civilization. There were men in them who had outgrown the magical practices that were never to die out among the peasantry. They had also outgrown the Olympian religion of Homer. Thanks to the poets, the anthropomorphic tendency of myth had overreached itself. The Greek imagination was, perhaps, unique in visual clarity, far surpassing the Roman in this respect. The supernatural powers had taken shapes so concrete and well defined that a Greek could recognize any god by sight . . . It was inevitable that, when
Editorial the gods had become completely human persons, some skeptical mind should refuse to believe that a thunderstorm in Asia Minor was really due to the anger of a deity seated on the summit of Olympus. [A hundred years later] Xenophanes attacked anthropomorphic polytheism with devastating finality: “If horses or oxen had hands and could draw or make statues, horses would represent the forms of the gods like horses, oxen like oxen” [s]. In summarizing the accomplishments Milesian philosphers, Cornford wrote:
of the
The significance of [their] cosmogony lies not so much in what it contains as in what it leaves out. Cosmogony has been detached from Theogony. There is not a word about the gods or any supernatural agency. This new form of thought brings into the field of everyday experience what had previously lain outside that field . . It was an extraordinary fact of rational thinking, to dissipate this haze of myth from the origins of the world and of life. Anaximander’s system pushes back to the very beginning the operation of forces such as we see at work in Nature every day [S]. We agree, therefore, with Dr Deppert and his colleagues, that vitalistic and physicalistic interpretations (myth and science), both of which attempt to satisfy our curiosity regarding the creation of the world, the causes of natural phenomena, and the origin of mankind, represent different paradigms. One could hardly disagree that religious and scientific approaches to these questions represent vastly different ways to explain natural phenomena. Adherents of the Darwinian explanation of the evolution of mankind base their theories on empirical observation, while those who find the answer to this question in the Book of Genesis rely on what they view as the divine word. Hesiod, who like today’s creationists, personified the forces governing the surrounding world, described an elaborate, often violent mythology that was based on traditional stories of conflicts among the gods. Two centuries later the Milesian philosophers depersonalized these forces, which they sought instead to understand in terms of conflicting principles, or elements, that reflected the operation of natural laws. This transition clearly marked a fundamental change in mankind’s attempt to understand our world and ourselves. As stated by Frankfort and Frankfort: This change of viewpoint is breath-taking. It transfers the problem of man in nature from the
Response
405
realm of faith and poetic intuition to the intellectual sphere. A critical appraisal of each theory, and hence a continuous inquiry into the nature of reality, became possible. [9]. What followed is familiar: The Atomism of Democritus, the great philosophic school of Athens-Socrates, Plato and Aristotle-and the flowering of rational medicine in Cos under Hippocrates. Science continued to evolve, with periodic interruptions and often long periods of inactivity, as an inquiry into the laws of nature that govern our world. In the more than 2500 years since the presocratic philosophers first enunciated the idea that the world was governed by natural laws, it can be argued that all scientific efforts have only added details as to what these natural laws are, and how they operate. This is, in fact, what Dr. Deppert and his colleagues have asserted. While the transition from mythical to rational explanations of nature might be viewed as the only true discovery in the history of science, and so the only paradigmatic shift, we maintain that this view contributes little to our understanding ofsubsequent developments in knowledge of the heart and circulation. In seeking to systematize the growth of knowledge of cardiovascular regulation, of what value is an analysis based in the view that there have been, in fact, onIy two paradigms (divine manipulation and natural lawsj in all of recorded human history? If these are the only valid paradigms, then the second is too large, and contains too much in a potpourri that obscures many dramatic advances in knowledge of the circulation. Do Dr Deppert and his colleagues deny that this science has changed its focus since the transition from mythology to the “mother” sciences of physics and chemistry in ancient Greece? Is it useful to include in a single paradigm all that has been learned about how the heart works-and perhaps all progress in biology-since the 6th Century B.C.? How does this help us as we seek to understand how science advances? Of what value is the assertion that all progress since Thales can be reduced to a single “physicalistic-reductionalistic” paradigm? Is it not more useful to consider our three paradigms that, while cumulative rather than dismissive, not only outline important shifts in the approach to biological regulation, but as
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A. M. Katz and L. A. Katz
shown below, help us to understand the evolution of three distinct systems that control biological function?
Does the KuhmfDeppert paradigm provide insights into the evolution biological regulation?
of
The reader who has toiled through these Editorials to reach this point will, we are sure, understand that the dispute centers on the meaning of the term paradigm. As Kuhn’s analysis of scientific revolutions and paradigmatic shifts are at the root of this dispute, we have no grounds to argue against the usage of this term advocated by Dr Deppert and his colleagues [I]. However, in yielding to Kuhn’s supporters, we must emphasize that their definition of a paradigmatic shift has stripped this concept of any useful meaning. In seeking to understand the growth of ideas in cardiovastheir broad definition cular regulation, requires not only that all progress since Harvey’s De Motu Cordis be considered as part of a single paradigm, but taken to its logical conclusion, that all progress since the transition from mythical to rational cosmogonies also be included in their huge “megaparadigm”. As we now show, subdivision of this body of knowledge into three systems of regulation (organ, cell, gene), which we have called paradigms, not only systematizes the developing knowledge of cardiovascular function, but also helps us to understand the manner by which these systems appeared during evolution. The conceptual sterility of the broadly defined paradigm proposed by Dr Deppert and his colleagues is heightened if we recall that their paradigm contains all known systems of biological regulation. In contrast, our paradigms describe three types of biological regulation (organ, cell, gene) that represent systems which almost certainly appeared at different times during the evolution of life on this planet [m. Regulation at the organ level (Starling’s Law of the Heart) could only have appeared after multicellular organisms had evolved a heart and circulatory system; this mechanism, therefore, could not have appeared much before 800 million years ago. Regulation by changing cellular biochemistry (myocardial contractility) is likely to be much
older, having probably appeared earlier in 1.8 billion years evolution, approximately ago, when eukaryotic cells, surrounded by semipermeable membranes containing pumps and channels, became able to control their internal environment. An even more primitive control mechanism would have been available to the earliest prokaryocytes, which lacking a highly developed cell membranes and the ability to regulate their internal environment, not only survived, but continued to reproduce, in a changing environment. The most primitive of these regulatory mechanisms, which almost certainly appeared at the dawn of life about 3.5 billion years ago, must therefore have been the ability to respond to changes in the physical and chemical state of the Archaeozoic seas by synthesizing altered gene products. We believe that a single paradigm that econompasses all regulatory mechanisms that operated since the dawn of life adds little to our understanding of the evolution of cardiovascular regulation. To accept the definition proposed by Dr Deppert and his colleagues, and include all systems of biological regulation (organ, cell, gene) that evolved over the past 3.5 billion years in a single paradigm, creates a universal paradigm so enormous, so all encompasing, as to have lost not only its usefulness, but probably any meaning at all. Yet when we view the regulatory mechanisms that appeared sequentially during evolution as reflecting a cumulative growth of biological control systems [2,.5,6], our three paradigms help us to understand not only how each operates, but also how they interact in the animals that inhabit today’s world.
What does the Kuhn/Deppert definition of a paradigmatic shift tell us about the progress of scientifk knowledge
According to Kuhn [3], a paradigmatic shift occurs when “an existing paradigm has ceased to function adequately in the exploration of an aspect of nature . . .“. According to this definition, a paradigmatic shift is dismissive in that a new paradigm is viewed as negating all previous knowledge. As already noted, however, this is not in accord with the laws of evolution, where such major advances as the development of multicellular animals
Editorial adapted, but did not eliminate, more primitive forms of regulation. Furthermore, Newton’s discoveries of the laws of Physics did not negate the work that had come before; nor did Einstein’s theory of relativity negate Newton’s work. In the case of the transition from mythological to rational explanations of nature described earlier, it would be certainly almost presumptuous-and incorrect-to state that there is nothing to be learned about evolution from a study of religion, or that mythology adds nothing to our understanding of science. Insofar as the development of knowledge, like evolution, is cumulative rather than dismissive, our examples of paradigmatic shifts provide a more useful depiction of progress in science than those of Dr Deppert and his colleagues. The value of our definition of paradigmatic shifts is, perhaps, seen most clearly when we consider its application to the diagnosis and therapy of human disease. In fact, we could not understand disturbances of the cellular systems in the myocardium if we were unable to describe the heart as an organ; nor would abnormalities in gene expression make any sense if were knew nothing of the properties of the individual myocardial cell. It is only by understanding all of these systems, using a model the additive nature of biological regulation, that we are becoming aware of the interplay between the diverse mechanisms involved in the pathophysiology and treatment of such clinical conditions as congestive heart failure [!&II]. Conclusions Dr Deppert and his colleagues conclude that: “the three theories of cardiac regulation listed by Dr Katz belong to one and the same paradigm” [I]. We have, in this Editorial Reply, avoided a direct challenge to this assertion; after all, it was Kuhn who selected the term paradigm to describe scientific progress, and Drs Deppert, Lohff and Schaeffer are lucid spokespersons for Kuhn. Yet, if we accept their definition, the Kuhn/Deppert paradigm becomes so inclusive that it would seem to contain all knowledge of the heart and circulation since Harvey, and probably Galen, or even Aristotle. Furthermore, their “megaparadigm” would include all regulatory
Response
407
mechanisms that have evolved since the life appeared on this planet. Finally, their definition paints an unrealistic picture of scientific progress as a dismissive process, rather than a cumulative growth of knowledge. Their analytic approach, therefore, does little to help us to comprehend the flow and development of the ideas that have led to our current understanding of cardiovascular regulation. Nor does such a paradigm offer much promise of future insights unless, of course, we move to a new scientific revolution as far-reaching as the Milesian shift from mythical to rational explanations of natural phenomena! We maintain, instead, that it is far more useful to divide this field into three natural paradigms (organ, cell gene) that describe not only the disciplines of physiology, biochemistv, and molecular biology, but also distinct systems of biological regulation that have appeared sequentially (although in reverse order: gene, cell, organ) during evolution! For this reason, we stand by the central concept in our previous Editorial [Z]: that the regulation of the work of the heart [2], the actions of angiotensin [.5j, and heart failure [q can be described by three distinct models of scientific activity (organ, cell, gene), each of which was s&iciently unprecedented to attract an enduring group of adherents away from competing models. Furthermore, as studies of the cell built on those of the heart as an organ; and later, when studies of the gene began to supplement those of the cell, each new approach was su#Eciently openended to leave all sorts of problems for the redefined group of practioners to resolve. Except that our models are cumulative, and not dismissive of one another, they conform closely to the definition of a paradigm provided by Kuhn himselc in fact, the clauses are taken from p. 10 of ref. 3! In closing, we should state most emphatically that the disputes in these Editorials must not obscure a very large area of agreement between ourselves and Drs Deppert, Lohff and Schaefer. It is important to understand the history and philosophy of science; indeed, the more we learn, and the faster that science progresses, the more important are clear landmarks. It was possible to fly an airplane without instruments in the early days of aviation, by “the seat of the pants”; but without a
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sophisticated set of instruments, it would be suicide to fly a supersonic jet in today’s crowded skies. The situation is no different in science: history and philosophy provide the essential beacons without which we may stray from the course of progress.
Acknowledgement The authors many forms article. Amold
thank Dr Phyllis B. Katz for of assistance in preparing this
M. Katz
and Laura
A. Kate
References DEPPERT W., LOHFF B., SCHAEFER J. The interdependence of paradigmatic shifts in the field of cardiovascular science. J Mol Cell Cardiol; Accompanying Editorial (1991). KATZ A. M. Molecular biology in cardiology, a paradigmatic shift. J Mol Cell Cardiol20, 355-366 (1988). Kuhn T. S. The Stmrture of.S&nf@ Revolution. 2nd Ed. Univ Chicago Press, Chicago (1970). KATZ A. M., KATZ P. B. Homogeneity out of heterogeneity. Circulation 79, 7 12-717 (1989). KATZ A. M. Angiotensin II: Hemodynamic regulator or growth factor? J Mol Cell Cardiol 22, 739-747 (1990). KATZ A. M. Is heart failure an abnormality of myocardial cell growth. Cardiology 77, 346356 (1990). KIRK G. S., RAVEN J. E. The Prcsocratic Philosphers. Cambridge, University Press (1960). CORNFORD F. M. Before and A&r Socrates.Cambridge, University Press (1932). FRANKFORT, H., FRANKFORT H. A., WILSON J. A., JACOBSEN T. Before Philosphy. The Intellectual Adventure of Ancient Man. Penguin Books, Baltimore MD (1946). 10 KATZ A. M. Cardiomyopathy of overload. A major determinant of prognosis in congestive heart failure. NEJM 322, lO&llO, (1990). II KATZ A. M. Changing strategies in the management of congestive heart failure. JACC 13, 512-523, (1989).
EDITORIAL What is a Paradigm
RESPONSE and When Does it Shift?
From the Cardiology Division, Department of Medicine, University of Connecticut. Farmington, CT, 06032, USA
hltroduction Drs Deppert, Lohff, and Schaefer [I] in comBiology in menting on the article “Molecular Cardiology. A Paradigmatic Shift”, [2] challenge our view that understanding of circulatory control has evolved through three paradigms, each of which was built on foundations set in place by earlier paradigms. Dr Deppert and his colleagues point out that our analysis is at variance with the views of T. S. Kuhn; [3] who stated that science advances through paradigmatic shifts in which each succeeding paradigm replaces those that had come before; according to Kuhn, science progresses through a series off revolutions, and not by the linear accumulation of knowledge. Kuhn states: “scientific revolutions are inaugurated by a growing sense, again often retricted to a narrow subdivision of the scientific community, that an existing paradigm has ceased to function adequately in the exploration of an aspect of nature to which that paradigm itself had previously led the way” [3].
What are paradigms, and how do they shift? In their thoughtful comments, Dr Deppert and his colleagues appear not to be in disagreement with our view that analyses of cardiac regulation have involved studies of the heart as an organ, of the function of individual myocardial cells, and of the variability of gene expression in the heart’s response to long-term and regional stimuli [2, q. Thus, the dispute centers on whether the systems: organ, cell, gene represent different paradigms, or whether, instead, they “belong to one and the same normal science of physiology which is dependent on the one paradigm of physics” [I]. 0022-2828/91/040403
+ 06 $03.00/O
As we emphasize later, our definition of three paradigms in cardiovascular science (organ, cell, gene) not only describes the history of scientific discovery in Cardiology during this century; in addition, our paradigms describe major shifts that took place during the evolution of cardiovascular regulation, but in the reverse order: gene, cell, organ. However, in contrast to Kuhn and his supporters, who assert that the growth of science is dismissive, our definition of a paradigm recognizes the cumulative nature of the advance of knowledge in the biological sciences [2]. This dispute could easily be resolved if the term paradigm had a clear and universally accepted meaning; it would certainly simplify this discussion if we could all agree on what we mean when we refer to paradigms and how they shift. As noted by Dr Deppert and his colleagues, however, Kuhn himself realized that this is an ambiguous term. Nor does the dictionary meaning provide much help: paradigm, which is derived from the Greek rtap& and 6Gypa (deigma (para = alongside), = sample, pattern), is most readily translated as a model, or example. How broad a model, and how inclusive an example is not implicit in this definition, so that for a given context the user is free to define the limits of this term. In seeking to resolve our dispute, therefore, we will allow Kuhn and his supporters to supply the definition; however, we do require that their definition facilitate a meaningful discussion of the history and philosophy of science. The Editorial by Dr Deppert and his colleagues discusses the meaning of Kuhn’s term, and provides a definition of a paradigm that they assert allows Kuhn’s concept of “paradigmatic shifts” to clarify the process by which knowledge of the circulation has advanced. However, as we point out in this Editorial :F 1991 Academic
Prrss Limited
A. M. Katz and L. A. Katz
404
Reply, the Kuhn/Deppert concept of paradigms, and how they shift, creates an epistemology that is of little use in describing either the development of knowledge of the cardiovascular system or the patterns by which biological regulation evolved through the sequential appearance of three distinct systems of biological control: gene, cell, orgak A definition
of a paradigm
As already noted, the dictionary definition and etymology of the term paradigm is so general as to leave us no choice but to accept the meaning provided by Kuhn’s advocates in the accompanying Editorial [I]. It was, after all, Kuhn who provided the term that we used in our earlier Editorial [Z], and Dr Deppert and his colleagues are speaking on Kuhn’s behalf. However, their definition: a “framework of the questions that are formulated within normal science, and the possible concepts that can lead to their solution”, like the dictionary meaning, is rather bland. Without further elaboration, even this redefined term cannot tell us whether our original article described “paradigmatic shifts” [Z], or simply different aspects of “one and the same normal science of physiology which is dependent on the one paradigm of physics” [I]. In the context of the present dispute, the test of their definition, and certainly its ability to help us to understand cardiovascular regulation, must be sought by examining the implications of the assertion that our three systems of regulation (organ, cell, gene) fit into a single paradigm [I]. In fact, as shown below, their definition of a paradigm so expands its meaning as to destroy its usefulness in analyzing the growth of knowledge of the heart and circulation.
Does the Kuhn/Deppert definition of a paradigm help us to understand the historical developmtnt of knowledge of biological regulation?
Dr Deppert and his colleagues assert that all in cardiovascular progress physiology described in our Editorial [Z], depending as it does on the “mother” sciences of physics and chemistry, falls within a single paradigm. Indeed, it appears that they would even include Harvey’s contribution as simply an
advance within a single paradigm, based on the principles of physics, that might even include the theories of Galen, who imagined the blood to ebb and flow, sometimes through invisible “pores” in the interventricular septum. The remarkable, indeed overreaching, inclusiveness of this definition obviates the usefulness of the concept of paradigmatic shifts in systematizing either the history or philosophy of this science. For, according to this definition, there has probably been only a single paradigm since the presocratic philosphers first postulated that natural laws, rather than whims of the gods, controlled the world around us. If, as suggested by Dr Deppert and his colleagues, all three systems of cardiovascular regulation (organ, cell, gene) are elements of a single paradigm, based on the “mother” science of physics and chemistry, then it follows that all progress in our understanding of circulatory regulation has taken place with a single normal science. One might reduce the argument of Dr Deppert and his colleagues [I] to a simple assertion: that the transition from mythical to rational explanations of nature represented the only paradigm shift in the history of science, or at least in biology. At one level, we agree with this assertion. The beginnings of Western science can be traced back over 2500 years, when Thales, Anaximander and Anaximenes in the Milesian School replaced mythological cosmogonies, such as had been described two centuries earlier by Hesiod, with a search for natural laws. As noted by Kirk and raven [7j, it was in Miletus that “the first completely rationalistic attempts to describe the world took place.“. The importance of these events, which occurred at the beginning of Classical Greek civilization, was described by Cornford: The Ionian Cities of Asia Minor were then at the height of Western civilization. There were men in them who had outgrown the magical practices that were never to die out among the peasantry. They had also outgrown the Olympian religion of Homer. Thanks to the poets, the anthropomorphic tendency of myth had overreached itself. The Greek imagination was, perhaps, unique in visual clarity, far surpassing the Roman in this respect. The supernatural powers had taken shapes so concrete and well defined that a Greek could recognize any god by sight . . . It was inevitable that, when
Editorial the gods had become completely human persons, some skeptical mind should refuse to believe that a thunderstorm in Asia Minor was really due to the anger of a deity seated on the summit of Olympus. [A hundred years later] Xenophanes attacked anthropomorphic polytheism with devastating finality: “If horses or oxen had hands and could draw or make statues, horses would represent the forms of the gods like horses, oxen like oxen” [s]. In summarizing the accomplishments Milesian philosphers, Cornford wrote:
of the
The significance of [their] cosmogony lies not so much in what it contains as in what it leaves out. Cosmogony has been detached from Theogony. There is not a word about the gods or any supernatural agency. This new form of thought brings into the field of everyday experience what had previously lain outside that field . . It was an extraordinary fact of rational thinking, to dissipate this haze of myth from the origins of the world and of life. Anaximander’s system pushes back to the very beginning the operation of forces such as we see at work in Nature every day [S]. We agree, therefore, with Dr Deppert and his colleagues, that vitalistic and physicalistic interpretations (myth and science), both of which attempt to satisfy our curiosity regarding the creation of the world, the causes of natural phenomena, and the origin of mankind, represent different paradigms. One could hardly disagree that religious and scientific approaches to these questions represent vastly different ways to explain natural phenomena. Adherents of the Darwinian explanation of the evolution of mankind base their theories on empirical observation, while those who find the answer to this question in the Book of Genesis rely on what they view as the divine word. Hesiod, who like today’s creationists, personified the forces governing the surrounding world, described an elaborate, often violent mythology that was based on traditional stories of conflicts among the gods. Two centuries later the Milesian philosophers depersonalized these forces, which they sought instead to understand in terms of conflicting principles, or elements, that reflected the operation of natural laws. This transition clearly marked a fundamental change in mankind’s attempt to understand our world and ourselves. As stated by Frankfort and Frankfort: This change of viewpoint is breath-taking. It transfers the problem of man in nature from the
Response
405
realm of faith and poetic intuition to the intellectual sphere. A critical appraisal of each theory, and hence a continuous inquiry into the nature of reality, became possible. [9]. What followed is familiar: The Atomism of Democritus, the great philosophic school of Athens-Socrates, Plato and Aristotle-and the flowering of rational medicine in Cos under Hippocrates. Science continued to evolve, with periodic interruptions and often long periods of inactivity, as an inquiry into the laws of nature that govern our world. In the more than 2500 years since the presocratic philosophers first enunciated the idea that the world was governed by natural laws, it can be argued that all scientific efforts have only added details as to what these natural laws are, and how they operate. This is, in fact, what Dr. Deppert and his colleagues have asserted. While the transition from mythical to rational explanations of nature might be viewed as the only true discovery in the history of science, and so the only paradigmatic shift, we maintain that this view contributes little to our understanding ofsubsequent developments in knowledge of the heart and circulation. In seeking to systematize the growth of knowledge of cardiovascular regulation, of what value is an analysis based in the view that there have been, in fact, onIy two paradigms (divine manipulation and natural lawsj in all of recorded human history? If these are the only valid paradigms, then the second is too large, and contains too much in a potpourri that obscures many dramatic advances in knowledge of the circulation. Do Dr Deppert and his colleagues deny that this science has changed its focus since the transition from mythology to the “mother” sciences of physics and chemistry in ancient Greece? Is it useful to include in a single paradigm all that has been learned about how the heart works-and perhaps all progress in biology-since the 6th Century B.C.? How does this help us as we seek to understand how science advances? Of what value is the assertion that all progress since Thales can be reduced to a single “physicalistic-reductionalistic” paradigm? Is it not more useful to consider our three paradigms that, while cumulative rather than dismissive, not only outline important shifts in the approach to biological regulation, but as
406
A. M. Katz and L. A. Katz
shown below, help us to understand the evolution of three distinct systems that control biological function?
Does the KuhmfDeppert paradigm provide insights into the evolution biological regulation?
of
The reader who has toiled through these Editorials to reach this point will, we are sure, understand that the dispute centers on the meaning of the term paradigm. As Kuhn’s analysis of scientific revolutions and paradigmatic shifts are at the root of this dispute, we have no grounds to argue against the usage of this term advocated by Dr Deppert and his colleagues [I]. However, in yielding to Kuhn’s supporters, we must emphasize that their definition of a paradigmatic shift has stripped this concept of any useful meaning. In seeking to understand the growth of ideas in cardiovastheir broad definition cular regulation, requires not only that all progress since Harvey’s De Motu Cordis be considered as part of a single paradigm, but taken to its logical conclusion, that all progress since the transition from mythical to rational cosmogonies also be included in their huge “megaparadigm”. As we now show, subdivision of this body of knowledge into three systems of regulation (organ, cell, gene), which we have called paradigms, not only systematizes the developing knowledge of cardiovascular function, but also helps us to understand the manner by which these systems appeared during evolution. The conceptual sterility of the broadly defined paradigm proposed by Dr Deppert and his colleagues is heightened if we recall that their paradigm contains all known systems of biological regulation. In contrast, our paradigms describe three types of biological regulation (organ, cell, gene) that represent systems which almost certainly appeared at different times during the evolution of life on this planet [m. Regulation at the organ level (Starling’s Law of the Heart) could only have appeared after multicellular organisms had evolved a heart and circulatory system; this mechanism, therefore, could not have appeared much before 800 million years ago. Regulation by changing cellular biochemistry (myocardial contractility) is likely to be much
older, having probably appeared earlier in 1.8 billion years evolution, approximately ago, when eukaryotic cells, surrounded by semipermeable membranes containing pumps and channels, became able to control their internal environment. An even more primitive control mechanism would have been available to the earliest prokaryocytes, which lacking a highly developed cell membranes and the ability to regulate their internal environment, not only survived, but continued to reproduce, in a changing environment. The most primitive of these regulatory mechanisms, which almost certainly appeared at the dawn of life about 3.5 billion years ago, must therefore have been the ability to respond to changes in the physical and chemical state of the Archaeozoic seas by synthesizing altered gene products. We believe that a single paradigm that econompasses all regulatory mechanisms that operated since the dawn of life adds little to our understanding of the evolution of cardiovascular regulation. To accept the definition proposed by Dr Deppert and his colleagues, and include all systems of biological regulation (organ, cell, gene) that evolved over the past 3.5 billion years in a single paradigm, creates a universal paradigm so enormous, so all encompasing, as to have lost not only its usefulness, but probably any meaning at all. Yet when we view the regulatory mechanisms that appeared sequentially during evolution as reflecting a cumulative growth of biological control systems [2,.5,6], our three paradigms help us to understand not only how each operates, but also how they interact in the animals that inhabit today’s world.
What does the Kuhn/Deppert definition of a paradigmatic shift tell us about the progress of scientifk knowledge
According to Kuhn [3], a paradigmatic shift occurs when “an existing paradigm has ceased to function adequately in the exploration of an aspect of nature . . .“. According to this definition, a paradigmatic shift is dismissive in that a new paradigm is viewed as negating all previous knowledge. As already noted, however, this is not in accord with the laws of evolution, where such major advances as the development of multicellular animals
Editorial adapted, but did not eliminate, more primitive forms of regulation. Furthermore, Newton’s discoveries of the laws of Physics did not negate the work that had come before; nor did Einstein’s theory of relativity negate Newton’s work. In the case of the transition from mythological to rational explanations of nature described earlier, it would be certainly almost presumptuous-and incorrect-to state that there is nothing to be learned about evolution from a study of religion, or that mythology adds nothing to our understanding of science. Insofar as the development of knowledge, like evolution, is cumulative rather than dismissive, our examples of paradigmatic shifts provide a more useful depiction of progress in science than those of Dr Deppert and his colleagues. The value of our definition of paradigmatic shifts is, perhaps, seen most clearly when we consider its application to the diagnosis and therapy of human disease. In fact, we could not understand disturbances of the cellular systems in the myocardium if we were unable to describe the heart as an organ; nor would abnormalities in gene expression make any sense if were knew nothing of the properties of the individual myocardial cell. It is only by understanding all of these systems, using a model the additive nature of biological regulation, that we are becoming aware of the interplay between the diverse mechanisms involved in the pathophysiology and treatment of such clinical conditions as congestive heart failure [!&II]. Conclusions Dr Deppert and his colleagues conclude that: “the three theories of cardiac regulation listed by Dr Katz belong to one and the same paradigm” [I]. We have, in this Editorial Reply, avoided a direct challenge to this assertion; after all, it was Kuhn who selected the term paradigm to describe scientific progress, and Drs Deppert, Lohff and Schaeffer are lucid spokespersons for Kuhn. Yet, if we accept their definition, the Kuhn/Deppert paradigm becomes so inclusive that it would seem to contain all knowledge of the heart and circulation since Harvey, and probably Galen, or even Aristotle. Furthermore, their “megaparadigm” would include all regulatory
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mechanisms that have evolved since the life appeared on this planet. Finally, their definition paints an unrealistic picture of scientific progress as a dismissive process, rather than a cumulative growth of knowledge. Their analytic approach, therefore, does little to help us to comprehend the flow and development of the ideas that have led to our current understanding of cardiovascular regulation. Nor does such a paradigm offer much promise of future insights unless, of course, we move to a new scientific revolution as far-reaching as the Milesian shift from mythical to rational explanations of natural phenomena! We maintain, instead, that it is far more useful to divide this field into three natural paradigms (organ, cell gene) that describe not only the disciplines of physiology, biochemistv, and molecular biology, but also distinct systems of biological regulation that have appeared sequentially (although in reverse order: gene, cell, organ) during evolution! For this reason, we stand by the central concept in our previous Editorial [Z]: that the regulation of the work of the heart [2], the actions of angiotensin [.5j, and heart failure [q can be described by three distinct models of scientific activity (organ, cell, gene), each of which was s&iciently unprecedented to attract an enduring group of adherents away from competing models. Furthermore, as studies of the cell built on those of the heart as an organ; and later, when studies of the gene began to supplement those of the cell, each new approach was su#Eciently openended to leave all sorts of problems for the redefined group of practioners to resolve. Except that our models are cumulative, and not dismissive of one another, they conform closely to the definition of a paradigm provided by Kuhn himselc in fact, the clauses are taken from p. 10 of ref. 3! In closing, we should state most emphatically that the disputes in these Editorials must not obscure a very large area of agreement between ourselves and Drs Deppert, Lohff and Schaefer. It is important to understand the history and philosophy of science; indeed, the more we learn, and the faster that science progresses, the more important are clear landmarks. It was possible to fly an airplane without instruments in the early days of aviation, by “the seat of the pants”; but without a
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sophisticated set of instruments, it would be suicide to fly a supersonic jet in today’s crowded skies. The situation is no different in science: history and philosophy provide the essential beacons without which we may stray from the course of progress.
Acknowledgement The authors many forms article. Amold
thank Dr Phyllis B. Katz for of assistance in preparing this
M. Katz
and Laura
A. Kate
References DEPPERT W., LOHFF B., SCHAEFER J. The interdependence of paradigmatic shifts in the field of cardiovascular science. J Mol Cell Cardiol; Accompanying Editorial (1991). KATZ A. M. Molecular biology in cardiology, a paradigmatic shift. J Mol Cell Cardiol20, 355-366 (1988). Kuhn T. S. The Stmrture of.S&nf@ Revolution. 2nd Ed. Univ Chicago Press, Chicago (1970). KATZ A. M., KATZ P. B. Homogeneity out of heterogeneity. Circulation 79, 7 12-717 (1989). KATZ A. M. Angiotensin II: Hemodynamic regulator or growth factor? J Mol Cell Cardiol 22, 739-747 (1990). KATZ A. M. Is heart failure an abnormality of myocardial cell growth. Cardiology 77, 346356 (1990). KIRK G. S., RAVEN J. E. The Prcsocratic Philosphers. Cambridge, University Press (1960). CORNFORD F. M. Before and A&r Socrates.Cambridge, University Press (1932). FRANKFORT, H., FRANKFORT H. A., WILSON J. A., JACOBSEN T. Before Philosphy. The Intellectual Adventure of Ancient Man. Penguin Books, Baltimore MD (1946). 10 KATZ A. M. Cardiomyopathy of overload. A major determinant of prognosis in congestive heart failure. NEJM 322, lO&llO, (1990). II KATZ A. M. Changing strategies in the management of congestive heart failure. JACC 13, 512-523, (1989).
