In Reply:

I thank Drs. Sette, Dorizzi, and Azzini for their foray into the history of the On the Shoulders of the Giants (OTSOG) aphorism and I appreciate their persistence in disseminating these fragments of insight to various audiences (compare their reference no. 5). Unfortunately, I find myself unable to follow them all the way back to Priscian, as the quote they provide (“grammatica ars … perspicaciores”) seems to bear little rapport to the OTSOG aphorism. More importantly, as the semantics of aphorisms are determined by the setting, I prefer to strictly separate the use of this aphorism in the scientific from its (mis)-use in the religious–spiritual and especially political context. In science, as opposed to religion, the view provided by the shoulders of giants permits the observer to see beyond the horizon of ones’ forebears. In religion, the authority of the giants may thwart skeptical examination of the canonical view and enforces conformity. Therefore, compiling the use of the OTSOG aphorism in these largely mutually exclusive endeavors of mankind is somewhat misleading. I cannot comment on its use in politics by the luminaries referred to by Drs. Sette and Dorizzi as neither this letter nor their reference no. 5 provide the necessary context.

Within the scientific framework, the exchange between Newton and Hooke remains, therefore, the relevant yardstick for the OTSOG aphorism. Importantly, however, one of the provocative novelties in Kuhn’s understanding of scientific progress is exactly the opposite of what the OTSOG aphorism commonly implies. Only “normal” science is cumulative and the tribute of “standing on your predecessors shoulders” makes literal sense. Revolutions and their associated paradigm shifts, however, are not. This paradoxical insight is what made Kuhn’s work brilliantly iconoclastic. I admit that the use of the OTSOG aphorism is problematic in the context of my review, including my own use of it, as OTSOG also paved the way into dead-ends as noticed by Thomas Butler more than half a century ago.¹  In fact, I intended its use only as an expression of my profound respect for all those scientists (including Claude Bernard) who, even when erring, contributed to the advancement of mankind’s quest for knowledge.

I appreciate Dr. Forman’s thoughts on my article. His mining-metaphor contains multiple appropriate analogies, whether or not it captures the essence of a specific historian’s interpretation of the history of science. Dr. Forman recognizes my vagueness with respect to identifying a paradigm shift within anesthetic research. Indeed, I am skeptical of the commonplace notion that the move to proteins as anesthetic targets represented a new paradigm. Prior to the “accidental” and short-lived hegemony of lipoid theories, a multitude of opinions about the nature of the anesthetic target (including proteins) coexisted under the umbrella of the “unified” paradigm. Only the temporary dominance of lipids and imperfect memory made the ascendance of proteins appear to be a paradigm-changing event. It is tempting to speculate that, had Nick Franks and the late Bill Lieb been able to publish their 1984 paper in the early 60s, it would have had a profound influence on the direction of research (possibly precluding the lipoid era altogether) but it would not have been seen as a paradigm shift. At least not in the meaning commonly attributed to Kuhn and embraced by me. A key characteristic of paradigm shift in its rigorous interpretation is “incommensurability” between paradigms. Incommensurability implies that workers in different paradigms will not be able to fully communicate with each other because of the fundamentality of the differences in their frames of reference. In my opinion, the acceptance of the protein hypothesis did not generate such a disruption in the flow of anesthetic mechanisms research, certainly not an alternative to Bernard’s unified theory. I do acknowledge, however, that one may take license in attributing a specific meaning to the term paradigm, as an analysis of Thomas Kuhn’s own usage of “paradigm” famously yielded more than 20 different meanings within his own highly acclaimed book.² 

Anyhow, the “paradigmatic” categorization of research itself is neither uniformly applicable nor universally accepted. Imre Lakatos³  uses the notion of research program, whereas Larry Laudan⁴  introduced the concept of research traditions. As opposed to a paradigm, more than one program or tradition are expected to coexist simultaneously in a given field of research. In my opinion, if a paradigm shift-like change occurred in our lifetime, it happened in the wake of the work of Ira Rampil⁵  and Joe Antognini⁶  on the importance of the spinal cord as locus of anesthetic-induced immobility: suddenly the unitary anesthetic state, with its continuous “depth” as indexed by immobility was fragmented into multiple components each with its own anatomic locus and mechanism. The unitary anesthetic state became an anesthetic syndrome and the notion of one universal anesthetic mechanism became obsolete. However, I do not want to belabor the analogy too much—biological sciences do not fit as neatly into Kuhnian paradigms as physics and chemistry do.⁷ 

I agree with Dr. Forman that unitary theories are not dead, although recently their focus has been narrowed to the most publicity-gathering component of general anesthesia: hypnosis disguised in its more attractive package of (un)consciousness. In this field, phantasies-disguised-as-theories are being fruitfully cultivated. Superficial simplicity and holistic elegance (e.g., a single elementary basis of consciousness for slime mold and Homo sapiens) couched in awe-inspiring quantum terminology, drawing support from eclectic collections of arbitrarily selected random observations from all spheres of science, render unitary theories popular among revelation-seeking consumers of popular science. The disconnectedness of such theories from contemporary neurobiology in general and anesthetic mechanisms research, in particular, remains largely overlooked by their aficionados. In complete disregard of Carl Popper’s thoughts, formulation of testable hypotheses (not to speak of actual experiments aimed at falsifying these theories) has never been a notable strength of unitary approaches. But are (sub)molecular unitary theories irrevocably dead? Are there levels of integration in complex nervous systems where a common network mechanism might be identifiable? My personal answer is a “probably yes” to both questions.

Let us also keep in mind that lack of recognition among contemporaneous peers, per se, does not invalidate a theory. The history of science provides many well-known examples of initial ridicule followed by delayed vindication. However, it is frequently forgotten that the unglamorous trash heap of science is overfilled with theories that were both dismissed by peers and did turn out to be abysmally wrong (anesthetic action by lipid elution being a handy example).⁸  In summary, however, the passage of time and the application of the scientific method⁹  will relegate barren ideas to the footnotes of history—be they unitary or multifactorial.