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INTEGRATIVE STUDY IN PHYSIOLOGY AND MEDICINE:

OBSTACLES ON THE ROAD TO INTEGRATION


By Joseph Engelberg

ABSTRACT

A recent report of the Long-Range Planning Committee of the American Physiological Society identifies physiology with “integrative biology” and urges that physiologists make their field “a unique branch of biology that deals with synthesis and integration.” However, certain institutional, procedural, and psychological obstacles lie in the way of those who would embark upon this task. The hurdles to be overcome include the following: the erroneous belief that biomedical scientists are already integrative; the inapplicability of the powerful methods of areas of specialization to integrative study; the fear of failure; the identification of integrative biology with the study of function; the disregard of hierarchy; the undervaluation of the abstract; the loss of a sense of mystery. These obstacles, though insidious, pervasive, and powerful, can be surmounted.

Keywords: Integration, Integrative biology, Integrative physiology, Integrative study,


Artists, by virtue of their sensitivity, are often the first to perceive portents: already in 1920 the poet Yeats (1921) surmised that “the center cannot hold.” The web of culture and civilization seemed to be tearing apart. Now, more than a half-century later, Yeat's concerns have become widespread. There is anxiety about the many forms of fragmentation – the fragmentation of knowledge, fields of study, cultures, institutions, societies. Accordingly, there have been urgent calls from scholars and others for a greater emphasis upon the integrative. What is called for is a greater nurturance of the cohesive and synthetic, and the development of integrative systems of thought (Folkow 1994, Schultz 1994). These systems are to supplement, not replace, the analytic and reductive.

These concerns were brought home to physiologists recently when the “Long-Range Planning Committee” of the American Physiological Society issued a “White Paper” on the future of physiology. The report called for a greater emphasis on the integrative dimension of the science (Giebisch 1990). The committee suggested, among other things, that the next revolution in biology would be in the integrative or organismic domain. If so, physiology “needed to become identified as a unique branch of biology which deals with synthesis and integration, and ultimately seeks to understand the functioning of whole organisms … .

Physiology may have missed out on the last revolution in biology, but it should not miss out on the next.” These remarks should not be construed too narrowly as applying only to the group of scientists which officially identifies itself by the name “physiologist.” They are applicable to all scholars (among them medical internists and other physicians of holistic perspective, physiologists, molecular biologists, biophysicists, theoretical biologists, systems analysts, etc.) who are concerned with the integrative dimensions of biological systems, whether these systems are cells or multicellular organisms. In what follows, the word “integrative biologist” refers to any and all of them.

Surprisingly, neither individually, nor at the level of their professional organizations, have integrative biologists been able to generate the energy and enthusiasm needed to act upon their integrative yearnings. What lies behind this lethargy? What are the factors – forces – which make it difficult for scholars to enter upon the integrative? This article is an attempt to identify some of the obstacles which may lie in the path of those who would pursue integrative concerns.

Integration The words “integration” and “integrative” appear in many contexts. They often refer to bringing two or more ideas which normally reside in realms distant from one another into relation with one another. One might relate, for example, a molecule which is found in a particular cell to some systemic effect in a multicellular organism; or one might attempt to bring two normally disparate scientific disciplines to bear upon a particular problem; or one might speculate how certain organismal subsystems are interconnected in some regulatory fashion as in a case of a feedback cycles which acts between a number of tissues or cell types; etc.

However, here the words “integration” and “integrative” will be used in a somewhat different, special sense. They will allude, as suggested above, to two types of systems (1) cells, and (2) multicellular organisms. They will also be relevant to social systems, whether human or animal, since in these the connections among the parts are also mediated by flows of information.

These systems are unique in the universe because their parts are integrated by streams of information which flow between them. When these streams are interrupted, the systems dis-integrate. Thus, the words “integration” and “integrative” will not be used in reference to a variety of stable systems whose parts are fundamentally kept together by physical forces (not by streams of information): atomic nuclei, atoms, molecules, viruses, heavenly bodies, galaxies, etc. They will likewise not be used to denote the process by which two or more scientific disciplines are brought together; interdisciplinarity is a different issue.

Integrative biology Science advances by rigorously adhering to the adage “divide and conquer.” In the pursuit of greater understanding, situations are analyzed mathematically, organisms are dissected, tissues sliced, cells isolated, homogenates fractionated, atoms “smashed.” Since the specific methods and concepts which underlie each of these fractionations are complex and difficult to master, specialization becomes unavoidable. Accordingly the culture of science itself fragments as new narrowly defined areas of specialization are continually born. And this is as it should be. However, it would be a mistake consider integrative biology to be just another area of specialization amidst or beside the other areas of scientific specialization. Being integrative, integrative biology lies at a different hierarchial level above, not alongside, the myriad areas of scientific specialization.

However, though intending to be integrative, contemporary integrative biologists, like other scientists and academics, tend to be pinned down to well-defined areas of specialization, and delimited areas of scientific thought – and find it inordinately difficult to break away. Why do integrative biologists, and specialists in general, find it so difficult to undertake integrative tasks? Why, in our time, is the realm of integration so very fragile and unstable? What makes the realm of specialization is so very stable?

The imperatives of specialization There are many social, economic, and psychological influences supportive of specialization. * Much security and satisfaction is to be derived from knowing more about something than almost anyone else. (The seeming security of the specialist may be somewhat of an illusion. It has been pointed out that most scholars/teachers are all only two or three questions away from ignorance and impotence. That is to say, as an authority on a subject they be able to answer quite well the first question posed by a listener to their lecture; a second, more searching, question already often tends to present difficulties to the speaker; a third, more searching question may not elicit an answer.)

  • Centers of higher learning are basically ensembles of areas of specialization. Specialists, therefore, have an easier time obtaining jobs, grants, promotions, tenure, and financial rewards.
  • Professional societies, special interest groups, professional meetings, journals, etc. are modes of communication via which the scholarly findings of specialists are distributed to their peers; integrators have more limited access to this system since their contributions tend not to fit any of the numerous categories of specialization.
  • The arcane knowledge and language of areas of specialization cause specialists to be esteemed by their colleagues, and by the laity – we admire most what we do not fully understand. Integrators, however, conduct their business using the language of everyday life, and therefore, do not seem particularly bright to those who specialize. So it comes about that integrators of all kinds – parents, administrators, politicians – have to put up with some disdain for the sake of their mission.

The sense of security provided by specialization is so comforting as to make scientists reluctant to venture beyond the bounds of isolated, well-demarcated problems and areas of concern. With such powerful forces propelling integrative biologists into specialized niches, is it a wonder that, for example, physiologists – a community of scholars historically identified with integrative science – find it difficult to generate the enthusiasm and energy needed for its basic mission?

An attempt to assail the forces just enumerated head-on would be futile; they have to be outflanked. Obstacles, however, stand in the way of such a flanking movement. Among them are the following: the illusion that biomedical scientists are already integrative; the belief that integrative study can be done on the side, at odd moments, requiring little time or effort; the perception that the scholarly tools of integration are those employed by the areas of specialization; the belief that integrative biology is merely the study of function; the fear of failure; and the loss of a sense of mystery. I will consider these in turn.

The illusion that we already are integrative One of the great obstacles which holds us back from getting started is the belief that as biomedical scientists we already are integrative. It is an illusion easy to come by.

Those of us who teach, say, entire physiology courses single-handedly find it easy to believe that we already are integrators: “I consider all organ systems; my lectures range over the molecular, cellular, and organismal levels. Clearly, I am integrative.” We forget that these courses are taught subsystem by subsystem. We rarely get down to the integrative, but are tempted to believe that if time were to become available for this purpose, we would do so. Yet, when on rare occasions time does become available, we find ourselves strangely incapable of coming up with a synthesis of significant import and power.

Similarly, as researchers we are tempted to believe that if only we were not constrained by the demands of time we would readily reveal the integrative to our students and to the world. Alas, we are forced by the nature of our investigations to focus on relatively narrow regions of thought; and as long as we devote most of our busy days to various specialized aspects of scientific research, how can we find the time to pursue studies of an integrative nature? And when as researchers we take occasional stabs at the integrative, are the results edifying?

While the assumption that we already are integrators debilitates us, humility and self-understanding can help lead us onto paths of integration. We would need to admit that when it comes to integration – we are ignoramuses; then, we would need to commit ourselves to working alongside (not ahead) of our colleagues, being willing to be among them, students among students.

Investment of time and energy The most limited research effort consumes enormous amounts of time and energy. Yet, when it comes to integration we are tempted to believe that it is something which can be done almost instantly, perhaps, on an occasional evening, weekend, vacation – or, even, in a motel room on the eve of a presentation. If integrative biology is to develop, it will require on the part of the individual investigator the same quantity and quality of thought, time, and energy now being expended on specialized research projects.

Hierarchy It is probably fair to say that all living systems are organized along hierarchial lines. Consider the human organism which is constituted of some 100,000 billion cells. These cells have to organize so that they can pursue common goals – interact in unified, orderly ways. What is the nature of this organization? By analogy we might ask what enables the many members of a human army to pursue their common goals? Can a single commander tell each member of the army what to do? Surely not; one commander cannot personally direct each of the 100,000 members. The problem is solved, of course, by creating a hierarchy: The army is divided into small groups – squads, platoons; platoons group to form companies, companies to form battalions, battalions to form regiments, regiments to form divisions, divisions to form corps, corps to form armies.

The purpose of the hierarchy is to structure and process the information which flows through the system. Unquestionably every cell of the human body (as well as every molecule in every cell) is also embedded in a hierarchy, a hierarchy far more complex and subtle than that of any army.

Strangely, the nature of this hierarchy is not the subject of significant discussion and investigation among integrative biologists, and conceptions held as to what constitutes hierarchy tend to the primitive Thus, the organizational hierarchy of the multicellular organism is conventionally portrayed as molecules forming cells, cells forming tissues, tissues forming organs, etc.; this anatomic notion is of little help when it comes to investigations of an integrative nature. Deficiencies in our understanding of hierarchy make it difficult, fo example, to clarify physiology's role in contemporary science. These deficiencies lead to confusion, among other things, as to where molecules fit into physiologic investigations, giving rise to the belief in some quarters that “physiology is chemistry.” This conceptual lack also deprives the word “integration” of much of its meaning, and makes it difficult to generate interest in integrative investigation. Clearly the study of hierarchy will be fundamental to the development of integrative thought.

A sense of mystery A science can become so matter-of-fact and practical that the great sense of mystery which gave it birth is lost. The mysterious is that region which lies at the true frontier of every science. However, as a science matures, an openness to, and a sense of awe before mystery tends to be replaced by a concern for the finite and practical, and a preoccupation with objects. The latter are things which can be held in the palm of one's hand: molecules, tissues, organs. Practical thinkers might have chided Isaac Newton: “Why bother about apples falling to the ground? Of course, everything falls to the ground! What is there to think about?”

Yet, much of what is of greatest significance to any science lacks this concreteness, and is often counterintuitive (Forrester 1969). Quantum mechanical wave functions, forces, electric fields, mathematical coordinate systems, phylogenesis, feedback cycles, information, hierarchy, etc. are not things which can be held in the palm of one's hand. These concepts were all born of a sense of wonder by thinkers who trusted abstraction and conceptualization. It will take this kind of thinking to discover, for example, the integrative matrix by means of which 1014 molecules become integrated into a cell, or 1014 cells become integrated to form a human organism. What theoretical physics is to physics, integrative biology is likely to be to areas of specialization in biology.

The exclusion of integrative concerns As has been said, almost every existing center of higher learning is but a collection of specialty groups. Such centers tend to nurture specialists, and tend to be inhospitable to those who would pursue integrative goals. Can these centers make room for the integrative, or will it turn out that integration and specialization are unable to coexist in the same institution? I do not know the answer to this question; possibly, new institutions may have to be developed. In my experience, however, the higher a person in an organizational hierarchy, the greater their understanding and appreciation of the integrative tends to be: governors, mayors, legislators, executives, university presidents, and other higher-level administrators (these are all integrators) seem to have no trouble understanding and supporting integrative initiatives; it is at the lower levels of organizational hierarchies that integration tends to be neglected, misunderstood, or held in scorn.

There is the problem of communication alluded to above. There are hundreds of thousands of specialized journals, and thousands of specialized professional meetings. Clearly, integration cannot be attained by scattering one's findings among these. New forms of intercommunication are needed. The kind of scholarly papers to which we are presently accustomed, consisting of narratives in which one or another topic is examined, may not play a major role in the realm of integration. As is discussed elsewhere (Engelberg 1994), in the integrative realm texts are more likely to take the form of case histories and sets of aphorisms to which commentaries are appended.

Is the development of an integrative science really needed? It can be argued that it is not needed. For it is true that science demands of investigators that they not only make discoveries, but that they make these discoveries (via reviews of the literature and the discussions of results) a part of the total fabric of science. If we think of science as a single patchwork quilt, then the integrations of science (just alluded to) involve the sewing of each new patch onto adjoining patches in the quilt. However, the persistent study of the constitution of matter at the level of quarks cannot inexorably lead, say, to an understanding of the political processes by which millions of diverse individuals form a single nation. Thus, the integration referred to in this article has nothing to do with sewing together patches of information; it has to do, rather, with the discovery and elucidation of principles of organization which make the existence of all living systems, from the cell upward, possible – and with the modes of discourse and education which can make this come about. This kind of integration is unlikely arise spontaneously from existing specialized, scientific undertakings.

The bottom line. As is the case with climbing, where it may be virtually impossible to scale a peak from one side of a mountain but quite possible to do so starting from the foothills on the other side, a prudent choice of approach is everything. Confidence can be taken from the fact that what is needed for the development of an integrative biology does not have to be constructed out of thin air; there is no need to “reinvent the wheel.” Over 3.7 billion years of biologic evolution – slowly and systematically – nature learned how to integrate molecules to form cells, how to integrate cells to form multicellular organisms, how to integrate organisms to form societies. This integrative wisdom which we now seek is embedded in numerous forms of life. Human society itself is permeated by the integrative. All around us are the integrators and integrative systems which make human existence possible: homemakers, administrators, politicians, statesmen, religionists, institutions, etc. The principles of integration we seek, the clues as to how to proceed, are to be found in many places.

In conclusion I have listed here a number of obstacles which would need to be overcome if the integrative dimensions of biology are to be developed. It is, of course, easier to list obstacles than to find ways in which they can be overcome, that is, implementation. As to implementation, I have spent some 25 years on experiments in integrative study; some of my findings have been published (Engelberg 198*, 1994) 198* is the medical case history paper **

ACKNOWLEDGEMENT

I would like to thank Dr. Donald T. Frazier, Dr. Diane Karius, Dr. David Randall, Dr. Dexter Speck for assisting in the development of this manuscript; Betty Smith for editing early drafts; and Carlene Hodges for her secretarial assistance.

REFERENCES

1. Yeats, W. B. Michael Robartes and the dancer. London: Macmillan, 1921.

2. Folkow, B. Increasing importance of integrative physiology in the era of molecular biology. NIPS 9:93-95, 1994.

3. Schultz, S. G. What's in a name? The Physiologist, 37:163-166, 1994.

4. Giebisch, G. H., et al. What's past is prologue. A “White Paper” on the future of physiology and the role of the

American Physiology Society. The Physiologist 33: 161-180, 1990.

5. Engelberg, J. The Nature of Integrative Study. Stillwater, OK: New Forums Press, 1994.

6. Forrester, J. W. Urban Dynamics. Cambridge, MA: MIT Press, 1969, p. 9-10, 109-110.

PHYSIOL\PAVOBS4?.MS 06/15/95


Joseph Engelberg

Department of Physiology University of Kentucky College of Medicine Lexington, Kentucky 40536-0084 TEL: 606-323-5563 FAX: 606-323-1070 E-MAIL: engelbej@uklans.uky.edu

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