Methodology and the emergence of physiological chemistry

Methodology and the emergence of physiological chemistry

E. GLAS METHODOLOGY AND THE EMERGENCE OF PHYSIOLOGICAL CHEMISTRY* Introduction AN ISSUE central to modern history and philosophy of science concerns ...

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E. GLAS METHODOLOGY AND THE EMERGENCE OF PHYSIOLOGICAL CHEMISTRY* Introduction

AN ISSUE central to modern history and philosophy of science concerns the bases for the appraisal of theories and lines of research 1. Since Popper 2 has denounced inductivism by showing the context-dependence of observation, alternative ways of conducting the scientific enterprise had to be looked for. According to P o p p e r 3 science contains no ' h a r d ' facts, well-founded on induction f r o m observation, but only conjectures that cannot definitively be verified, at best they can definitively be falsified. But, owing to the context-dependence of the definition of observational evidence, it seems often possible to immunise a theory against falsification instead of accepting its refutation. Methodology is concerned with, a m o n g other things, finding means to evaluate theories and lines of research while taking into account the contextdependence of observation. In this article I intend to analyse a stage in the early development of physiological chemistry, viz. the period of about 1 8 4 0 - 1860. I have chosen this period because only during the 1830's sufficiently accurate knowledge of the elementary composition of a sufficient number of physiologically relevant substances became available to serve as a relatively solid basis for the erection of physiological-chemical theories. Two theories and lines of research prevailed during this period: those of Gerrit Mulder and of Justus Liebig. I have discussed these theories in previous articles4; in the present essay I want to focus on the methodological aspects: how were these systems arrived at, how did they define their observational evidence, what role did metaphysical arguments play, what impact did they have on contemporary physiology and how are they to be evaluated? In order to demarcate further the context for this article some preliminary methodological considerations may be useful. P o p p e r 5 claims that a theory has empirical content only if, and exactly in so *Department of General Sciences, University of Technology, Julianataan 132, Delft, The Netherlands. 'For review, see W. Stegmtlller, 'Theorie und Erfahrung' in Probleme und Resultate der Wissenschaftstheorie und analytischen Philosophie, Bd. II/2 (Berlin, Heidelberg, New York, 1973). 2K. Popper, Logic of Discovery (London, 1959) originally published in German in 1934. Cf. also: N. R. Hanson, Patterns of Discovery (Cambridge, 1958). 3K. Popper, Conjectures and Refutations (London, 1963). 'E. Glas, Janus LXlI (1975), 289; LXIII (1976), 27, 275. sOn the Popper - Kuhn - Lakatos debate, cf. the contributions of these authors in Criticism and the Growth of Knowledge I. Lakatos and A. Musgrave (eds.) (Cambridge, 1970). Stud. Hist. Phil. Sci., Vol. 9 (1978), No. 4. pp. 291 - 312. © Pergamon Press Ltd. Printed in Great Britain.

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far as, it exposes itself to falsification. Immunising a theory against falsification implies, then, impoverishing its empirical content. Theory-appraisal and rational preference are founded on degrees of corroboration, which Popper defines as the measures according to which theories expose themselves to falsification and have stood up to it. Popper takes it for granted that it is always possible to judge a theory on the face of the empirical evidence acquired in the context of that theory. Kuhn 6 on the other hand, thinks that science is not primarily guided by falsification as a means of increasing empirical content, but by the puzzlesolving faculty of some frame or matrix of reference which, during some period, is taken for granted in a scientific community (the ' p a r a d i g m ' ) . The paradigm implies a metaphysical position, a value concept and a number of exemplary instances of how puzzles are to be solved. A scientific revolution may occur when the paradigm ceases to provide the means for solving the puzzles that are considered as relevant in the changed historical situation. A new paradigm may then come to supersede the old one, owing to its better puzzle-solving ability in the changed context. Paradigms are, according to Kuhn, incommensurable with respect to the observational evidence. They lack logical contact, as their adherents do not use terms in the same sense. It is thus not accumulation of knowledge, but shifts of 'Gestalt', that the history of science teaches us. Fairly obviously, P o p p e r ' s view is based on logic and the apriori identification of empirical and falsifiable content, implying a normative criterion for 'genuine' science. We want now to examine how the developments to be surveyed are to be accounted for in the light of falsificationism. I shall demonstrate that Liebig's as well as Mulder's theories had lost virtually all their falisifiable contents by about 1860; yet this immunisation did not prevent them f r o m providing the basis for fruitful developments during the 1860's. Liebig's and Mulder's systems exhibit paradigm-like features in several respects: the two authors defined their observational evidence in quite different ways and exhibited altogether different fundamental attitudes with regard to the metaphysical basis and the values of science. In what follows, 'metaphysical' will refer to the general and mostly implicit or covert ideas scientists may have as to the sort of things reality is composed of and the mode of argumentation most adequate to grasping reality conceptually. We must examine whether metaphysical positions were really incommensurable, or whether they reflected methodological problems thrown up by science at a certain stage and in principle decidable by science itself. A considerable part of what follows will be devoted to answering this ques-

ST. Kuho, The Structure o f Scientific Revolutions (Chicago, 1962); and note 5.

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tion. Inevitably, every biochemical method or theory reflects some metaphysical attitude, either explicitly or implicitly, with regard to the question of the applicability of the methods and theories of (inorganic) science to certain aspects of life. Mostly the metaphysical implications o f methods and theories are far more finely shaded and richer than is stated explicitly by their authors. I have ventured to reconstruct those of Liebig and Mulder on the basis of both their more explicit utterances and their scientific practice. Although conjectural, such a reconstruction may elucidate some traits of their thought that would otherwise remain concealed. It has been stated, for example, by a number of historians r, that Liebig's explicit statements about and usage of the notion of vital force do not allow of extracting a coherent and unified view. Yet, as I shall demonstrate, reconstruction of his position on the basis of both his scientific practice (not merely his usage of the notion of vital force) and his more explicit utterances, reveals a coherent and unified view after all. German physiological chemistry during the 1860's owed its success to a combination of Liebig's and Mulder's methodologies, elaborated in particular by C. G. Lehmann early in the 1850's. As I shall demonstrate, such 'syntheses' of opposing methodologies were possible by relativising their metaphysical presuppositions in the face of the development of science. A number of Liebig's guiding metaphysical principles were, for instance, replaced by scientific principles derived from thermochemistry and thermodynamics. For such syntheses to be possible, the competing systems have to be somehow commensurable. Yet the degree of corroboration of the two theories as such cannot be the standard by which they enter into logical contact. It might perhaps be thought that Lakatos's methodology of research programmes 8 is here applicable. Lakatos focuses on larger complexes of theories, called 'research programmes', which share some common hard core as a frame o f reference for theory appraisal. Appraisal is not based on the falsifiability of individual theories, but on the positive or negative heuristics of research programmes. These heuristics are still interpreted, however, as tendencies toward increase or decrease of falisifiable contents. I do not think that it is easy to assign to Liebig's and Mulder's systems a common frame of reference, unless one considers physiological chemistry merely an appendix to 'established' science and, accordingly, 'established science' the common hard core of the two new-emerging systems. Such an interpretation would undercut the internal logic of the development of this

'Most explicitlyby T. O. Lipman, Isis LXIII (1967), 167. al. Lakatos, Proc. Aristot. Soc. LXIX (1968), 149; History of Science and its Rational Reconstructions; in Method and Appraisal in the Physical Sciences C. Howson (ed.) (Cambridge, 1976); and note 5.

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discipline. There is, I think, another basis for logical contact: the degree of abstraction employed in a theory. Liebig's context was that of classical particle mechanics; he tried to look abstractly upon vital p h e n o m e n a at this level with the aid of a number o f metaphysical arguments. Mulder, on the other hand, looked upon those p h e n o m e n a at the far less abstract level of qualitative chemistry and energetics. Now, it belongs to the very essence of physiological chemistry to abstract vital processes in such a way as to make them interpretable in terms of a branch of (inorganic) science. It is only natural that scientists initially appealed to metaphysical arguments in order to effect such an abstraction. Owing to Liebig's and Mulder's different metaphysical outlooks, the falsifiable contents of their systems were not commensurable. But their degrees of abstraction - mechanics being ' m o r e abstract' than qualitative chemistry - - provided a standard for logical contact. It is not feasible to decide in advance whether it is wiser to assume a more abstract standpoint (e.g. that of particle mechanics) and next to try to reduce some aspects of life to statements in mechanics, or to assume the far less abstract standpoint of qualitative chemistry and to try to interpret aspects of vitality in that context. The latter approach seems less risky but also far less universal than the former. I think that, given a certain stage in the development of physiological chemistry, this difference in levels of abstraction is more important for appraising the potentialities of methods and theories than the t e m p o r a r y heuristic of either of the lines of research. A successful reduction of aspects of vital p h e n o m e n a to statements of chemistry provides also a guideline for the more abstract line of research. Irreconcilable metaphysical attitudes may be partially reconciled once it has been realised that some statements of the one theory might be reducible to statements of the other, at another level of abstraction. Liebig, for example, partly for metaphysical reasons, denied the molecular nature of proteins. This metaphysical position was irreconcilable with Mulder's view, who considered vital processes primarily as manifestations of molecular-chemical actions. Initially there was no possibility o f reconciling the two viewpoints, but once some aspects of vital p h e n o m e n a (such as dietetics) proved interpretable in terms of molecular protein chemistry, Liebig's adherents had to account for this fact in their attempts at interpreting vital p h e n o m e n a in terms of mechanics. Every successful reduction thus furnishes scientific guidelines for the ways in which phenomena have to be abstracted to reach various levels of science. Incommensurable dogmatic metaphysical positions are increasingly transformed into approaches at levels of abstraction measurable by the same standard. Dogmatic controversies increasingly are replaced by scientific discussions about possible reductions, on the basis of the increasing number of successful partial reductions. By 'reduction' I shall

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understand the violation of the immunity of conceptual contexts by correlating in a testable way their constituent notions, statements, etc. with those of other contexts. Within physiological chemistry (not in philosophy) vitalism-mechanism debates have fallen more and more silent during the present century, not because these metaphysical controversies have been solved, but because the need for assuming any metaphysical attitude while studying vital phenomena becomes superfluous once a sufficient number of partial reductions have been undertaken to serve as a basis for appraising the possibilities of various abstract approaches. In what follows I shall trace the growth of the two physiological-chemical methodologies and examine the more explicit philosophical statements of their authors in order to single out the metaphysical principles they applied in abstracting vital processes. Thereafter I shall examine the impact of the two systems on the further development of physiological chemistry during the 1860's and the ways in which they were modified to face the changed problem situation of this discipline.

The Initial Stages and the Role of Organic Chemistry For the purpose of this article I shall start my account at the moment when the problem of demarcating vitality and inanimate phenomena came to be stated scientifically, i.e. when it ceased to be regarded one-sidedly either as non-existing (dogmatic materialism) or as insuperable (dogmatic vitalism). In the first decades of the nineteenth century vitalism prevailed on the basis of a romantic Naturphilosophie. Even opponents to this philosophy ( e . g . J . J . Berzelius) silently assumed, at this time, that in vital processes (among them the synthesis of organic substances) an irreducible force or property was operative, the "vis vitalis" or "nisus formativus'. (Berzelius's later position is discussed further on.) This situation gradually changed, once the results of elementary analysis (since the late eighteenth century) were applied as a means of visualising physiological transformations (Hall~, Prout, Berzelius, Tiedemann, Gmelin, etc.)L Yet, the laws underlying such rearrangements were not considered fully reducible to statements of chemistry; they mostly continued to be regarded as guided by some vital principle. Berzelius, e.g., initially treated of organic chemistry as a branch of physiology. Wt~hler's synthesis of urea (1828) did not seriously shake the general vitalistic opinion at that time. '° Only in the course of the fourth decade a physiological-chemical

9F. L. Holmes, Isis LIV (1963), 50. ~0j. H. Brooke, Ambix XV (1968), 84.

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methodology was set up (by G. J. Mulder) which did away with the dogmatic antagonism between materialism and vitalism and assumed, ultimately, a positivist character. I shall now trace the growth of Mulder's position and the philosophical implications of his methods and theories.

Mulder's 'positivism' For a proper understanding of Mulder's position it is of some importance to note that he initially was a medical man. When cholera swept Europe in 1 8 3 2 - 3 3 , he started a series of investigations into the chemical status of this disease." He found that it could be conceived of as a reversal of digestion: instead of food uptake by the blood from the digestive tract, blood serum appeared to be released into the tract. This discovery enabled him to explain a number of symptoms, but Mulder thought it wise to attribute these to a nervous disorder instead. Fear of being accused of 'iatrochemistry' by his colleagues must be held responsible for this obvious inconsistency. In medical circles Naturphilosophie was still influential; chemical 'handicraft' was considered unworthy of a medical man. A doctor was supposed to philosophise about organic 'forms' and abstract analogies. As plants have no nerves, Mulder felt less frustrated while investigating plant physiology. After previously having undertaken various analyses of plant pigments, '2 he arrived at a physiological-chemical theory of photosynthesis by 1834. '3 Mulder started from the working hypothesis that chlorophyll and the autumnal pigments are the same basic substance under varying degrees of oxidation. This hypothesis was suggested to him by the apparent analogy between the series of autumnal colours and the solar spectrum (both being g r e e n - y e l l o w - o r a n g e - r e d ) . Since in the case of the solar spectrum this series takes root in the continuous variation of a single parameter (the wavelength of light), the autumnal colours might similarly be attributable to a single parameter. And, in the post-Lavoisier era, it was only natural for him to think of the oxygen content. The hypothesis was supported by a series of experiments on oxidation and reduction of plant pigments in extracts. Mulder held chlorophyll to be the primary product of photo-reduction (an obvious confusion with the starch present in chloroplasts), and the precursor of all vegetable substances with low levels of oxidation. He thought that during summer reductive synthesis and oxidative modification were in dynamic equilibrium, whereas in autumn ox" G . J. Mulder, Nat. Scheik. Arch. 1 (1833), 1. " G . J. Mulder, Bijdr. Nat. Wet. VII (1832), 82. '~G. J. Mulder, Nat. Scheik. Arch. ii (1834), 1.

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idation was supposed to overcome photoreduction. Hence chlorophyll then passed through the various autumnal modifications to be ultimately completely oxidised. It struck Mulder that both the reductive and the oxidative processes involve the action of light; moreover, both processes result in colour formation, whereas in inanimate nature light tends to destroy all colours. Obviously the one-way passage of 'inanimate' processes is abandoned in the domain of life and made subservient to essentially reversible processes, exhibiting a state of dynamic equilibrium. Subsequently Mulder was to conceive of the action of light as 'catalytic'. In surveying this earliest physiological-chemical investigation we note that Mulder was far from seeking to reduce the whole of vital phenomena to chemical processes. But insofar as life involves material transformations, it may be studied, through the means of chemistry. Mulder's presupposition was that the pure chemical substances extracted from living things may be held to correspond to the substances constituting those living things, so that chemical experience with the former is translatable into traits of the latter. This validation of 'proximate analysis' (as opposed to 'ultimate' or elementary analysis) was fundamental to Mulder's line of research. It contrasted strongly with Liebig's views (to be discussed presently), but was fully in line with such important achievements as Chevreul's studies on fats. 14 With his analyses of silk fibres Mulder opened a series of researches into the proximate principles of animal substances. 15 Here he started from the working hypothesis that the formation of these threads is analogous to the clotting of blood. When leaving the animal, the thread is in a semi-liquid state. Upon coming into contact with the open air it clots while extruding the water and its solutes. Mulder could indeed demonstrate that the exterior of the silk fibre is water-extractable, whereas the interior consists of insoluble 'fibroin.' Just as in his investigations on photo-synthesis, Mulder did not aim at a chemical reduction of the process, but arrived at his theory by reasoning on analogy and subsequent testing. Obviously inspired by his successes so far, Mulder next tried to devise methods for the 'proximate' and 'ultimate' (elementary) analysis of the preeminently 'living' substances, the proteins. He felt that only knowledge of the constitution and chemical properties of these substances could eventually furnish a sound basis for the erection of physiological-chemical theories. In 1838 he published his famous 'proteine theory' (discussed in some detail by me in another article16); during the years 1838- 48 it was developed further i'M. E. Chevreul, Considdrations sur l'Analyse Organique et sur ses Applications (Paris, 1824). 'SG. J. Mulder, Nat. Scheik. Arch. III (1835), 93; Ibid. IV (1836), 268. 'eE. Glas, Janus LXII (1975), 289.

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and applied to physiological questions. This resulted in a voluminous textbook, 17 entitled 'Proeve eener algemeene physiologische scheikunde' (also published in English under the title 'The Chemistry of Vegetable and Animal Chemistry' and in German as 'Versuch einer allgemeinen physiologischen Chemie'). By 1843 his methodology had been fully developed; its philosophical purport was stated more explicitly in an academic lecture of the year 1849.18 In his earlier, medical, work Mulder had used the notion of a vital force, but after having developed his own methodology this conception was abandoned. In Mulder's view vital actions are the result of chemical actions working at a high level of organisation under (practically) irreducibly complex circumstances. It is these boundary conditions that we lose sight of; by themselves the vital actions are no more mysterious than the processes in inanimate nature. Accordingly, the objective of physiological chemistry is defined by Mulder as 'the elucidation of the import of complex material conditions in the manifestation of chemical actions ''9. To undertake this, the chemical substances of living matter must be isolated, purified and analysed; their chemical properties must be investigated and their localisation and function in the fine structures of the tissues must be unravelled. In all this we should stick as closely as possible to chemical experience; in the circumstances of that time Mulder considered it highly premature to think already of theorising. It is obvious that this statement of a physiological-chemical methodology was not elucidated abstractly, but as the outcome of his previous work involving chemical experimentation on 'living' substances. It was a declaration of a physician's respect for the complexity and autonomy of life. Mulder's previous researches had strongly suggested that it is essentially material processes that give rise to life; yet the results of these processes are determined by the complex circumstances in which they take place. If it is not the forces at work but the boundary conditions for their action which are unique, we cannot investigate these forces other than by studying their effects. In Mulder's view, the greatest heresy in science is the arbitrary definition of a force, subsequently attributing to it properties as the phenomena require for their explanation 2°. His 'philosophy' amounts to saying that the distinction between 'cause' and 'effect', as well as between 'force' and 'resultant action', is a feature of our way of abstractly looking upon phenomena. In the above-mentioned lecture Mulder interpreted the notion of 'force' as 'basis for action', and then went on (my translation): "Rotterdam, 1843 - 1850; G e r m a n ed., translated by Moleschott (Braunschweig, 1 8 4 4 - 1852); English ed., translated by Fromberg (Edinburgh, 1845 - 1849). 'SG. J. Mulder, De weg der Wetenschap, zijnen leerlingen opnieuw aanbevolen (Rotterdam, 1849). '~G. J. Mulder, Proeve etc., note 17, pp. v - i x . 2°Ibid. pp. 1 - 3 , 75.

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Science implies aiming at reduction of the number of forces, i.e. at deriving as many things as possible from one or a few bases of action. But this should not be called searching for the connection between cause and effect, for we imagine these causes no different from what the effects have made us imagine. Knowledge of the cause is merely a representation of the universal that has arisen from the particular. So, if this representation is construed on the [basis of the] particular, it is absurd now to reconnect the cause with the particular, al Accordingly, Mulder adhered to an inductivist positivism. In his view deduction is only possible after the establishment o f inductive laws allowing of the mathematical deduction of novel expressions. When these novel expressions are compared with nature, they serve both for the verification of the original inductive laws and the extension of their field of application.

Liebig's 'rationalism' From about 1840 onward Justus Liebig published on protein chemistry, obviously under the influence of Mulder's achievements. 22 However, his line of research was altogether different from Mulder's. He regarded all proteins as isomers and claimed that, in order to formulate physiological theories, it suffices to take into account only the relative elementary compositions. 23 Liebig considered Mulder's physiological-chemical method a welcome alternative to the 'quarrel about numbers' into which theoretical organic chemistry tended to degenerate. From the outset he conceived of his own approach to physiology as an alternative to 'crude empiricism', as stated in a letter to Pelouze (1841): II se fait une grande reforme dans la physiologie, et cette reforme se base sur la chimie organique. C'est bien un triomphe sur l'empirisme et sur les th6ories creuses qu'ils se sont imagin~. 2' Rather than this poor empiricism, the 'analytic-compository' method of classical mechanics (Galileo, Newton) should be elaborated in physiology: es kann nut geschehen wenn wir das anscheinend Ver~inderliche dutch Zahl, Mass und Gewicht festzuhalten suchen, dutch die Methode yon Galilei und Bacon von Verulam, deren Sch~lrfe, Bestimmtheit und Ni~tzen sich in der Chemie so gl~inzend beth~itigt hat. 25 The name of Bacon was not very appropriate here, as Liebig later (1863) 2e preferred to attack empiricism by denouncing its British forerunner.

2'G. J. Mulder, De weg etc., note 18, p. 40. 22j. Liebig, Ann. Chem. Pharm. XXX¥11I (1841) 203. 23Cf. E. Glas, Janus LXIII (1976), 27. 2'Reprinted in F. L. Holmes, Claude Bernard and Animal Chemistry (Cambridge, 1974), pp. 461 - 462. 2sj. Liebig, "Bemerkungen tiber das Verhillmiss der Thierchemie zur Thierphysiologie, 1844,' in Reden und Abhandlungen, 2nd ed., (Wiesbaden, 1965), p. 70. 26J. Liebig in Reden und Abhandlungen, note 25, pp. 220, 255,280.

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According to Liebig, science inevitably has to start from induction via observation. Yet inductive inferences are 'unbestimmt' (indeterminate) and 'maasslos' (not quantitative). Science is concerned with magnitudes, however; the intellect strives for quantitative notions allowing of deduction (compare the rationalist dictum that clarity and distinctness are the marks of scientific knowledge): die Deduction unter der Leitung des Verstands analysiert und begrenzt, und ist bestimmt und maassvoll?' In emphasising the pre-eminence of the intellect in the scientific enterprise Liebig went so far as to claim that the sole difference between ancient and modern science consists in the degree of adequacy o f the conceptual apparatus. Aristotle's observations were alright, even his logic was correct, but the concepts of modern science are clearer and far more distinct. Thus, the progress of science does not depend on improving observation; observation is only useful for science if put in a rational context by the intellect? 8 In physiology the only quantitative items available were the percentages by weight of the elements in physiologically relevant substances, not only the pure 'proximate principles', but the 'organised principles' (tissues or even whole organs) as well. In order to deduce physiological theories on this basis, Liebig was constrained to appeal to a number of 'metaphysical' guidelines or 'beliefs '29. One such belief was the alleged 'economy' of vital transformations:Liebig thought that material rearrangements in organisms take place in such a way as to require a minimum of exchange of elements. A related argument was used when he claimed that only fats and carbohydrates are subject to physiological combustion, whereas the proteins are taken up as 'plastic' elements of the tissues. This belief, basic to his metabolic theories, had been founded exclusively on the allegedly bad combustibility of proteins as compared to fats and carbohydrates. Another central belieff ° was the alleged 'inertia' of chemical molecules, implying that rearrangements take place only if an 'impetus' (of force) or 'amount of motion' (of colliding molecules) is transferred to them which overcomes their 'Beharrungsverm0gen' (inertial capacity). This conception was fundamental to his theories about fermentation and enzymic processes. In the next section I shall demonstrate that Liebig's conception of a vital force was fully in line with these beliefs so fundamental to his line of reasoning. None of them was founded on experimental data; on the contrary, they 2,j. Liebig in Reden und Abhandlungen, note 25, p. 296 (1865). 2"Ibid. pp. 3 1 0 - 3 2 9 (1866). '~J. Liebig, Animal Chemistry (translated by Gregory), (Cambridge, 1842; facs. New York, London, 1964). 30j. Liebig, Ann. Pharm. XXX (1839), 250, 363; cf. E. Glas, Janus LXII! (1976), 275.

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were handled as a context for defining his observational evidence. In previous articles 31 I have discussed Liebig's 'statical' mode of defining the empirical basis of his system and his 'statistical' model of reasoning. It must suffice here to state that Liebig's empirical evidence consisted in the balances o f elementary composition between the various substances participating in physiological transformations. He deduced his physiological theories starting from these balances and reasoning 'statistically' along the various metaphysical guidelines indicated above. Statistically, when for example he established metabolic transformations by computing which rearrangement of elements was the more 'economic' one with regard to the percentages of the elements constituting the substances involved. Views on Vitality

In order further to illustrate my point that philosophical statements made by practising scientists in the context of their studies reflect their favoured lines of research and reasoning rather than being elucidated abstractly, I shall now show that Liebig's alleged vitalism and Mulder's alleged materialism are, in point of fact, idling designations 32. Berzelius thought, during the last part of his life, that within the living organism the properties of chemical substances are specifically modified on account of the complex circumstances existing there. He abandoned the conception of a vital force and replaced it by the notion of 'catalysis '33. Although the mode of operation of the catalytic force was unknown, Berzelius held it responsible for the typically physiological contact actions (a detailed account of the various options about physiological contact actions I have presented elsewhere) 3°. This idea was taken over e.g. by R. F. Marchand (1844) 34. Mulder took a similar view, but considered Berzelius's conception of catalysis - - as a manifestation of electric forces - - inadequate. According to Mulder such contact actions are more appropriately regarded as facilitated chemical interactions in which the catalyst somehow enables the reaction partners to exchange the 'energy' (not Mulder's term) of the reaction?L Mulder, at that time (c. 1844) 3e, believed in abiogenesis, and described it in terms of what nowadays is called 'auto-catalysis'. He thought, for example,

3'E. Glas, Janus LXIll (1976), 27, 275. ~2T.O. Lipman, Isis LXII! (1967) 167;F. Gregory, Scientific Materialism in Nineteenth Century Germany (Dordrecht, Boston, 1977), pp. 84-85. 33j. j. Berzelius, Jahresber, XV (1836), 237; Ann. Pharm. XXXl (1839), 1; cf. A. Mittasch, Berzelius und die Katalyse, Leipzig, 1935; B. S. Jc~rgensen,J. Chem. Educ. XLII (1965), 394. 3'R. F. Marchand, Lehrbuch der physiologischen Chemie (Berlin, 1844), pp. 52- 57. 35Cf E. Glas, Janus LXIII (1976), 282-283. 36G. J. Mulder, Proeve etc., note 17, pp. 82-85.

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that the mould of cheese originated in the cheese molecules. His analyses taught him that moulds and yeasts are extremely rich in proteins 3r. They stand, Mulder claimed, on the very line of demarcation between animate and inanimate things. He had observed that warmth is an important factor in the genesis of moulds and yeasts, and as warmth was known to induce chemical processes Mulder thought that in abiogenesis the cheese molecules are initially excited by warmth. This results in an intramolecular rearrangement which alters the chemical nature of the molecule. This shift of the 'internal circumstances' in the cheese molecule again induces a transformation, etc. Thus, owing to auto-catalysis, a mould eventually arises f r o m the cheese. It is, as it were, an 'actualisation' of the 'potentialities' of organic matter by means of catalysis, i.e. facilitated transformation of chemical energy. The very same thing was supposed to occur in the development of an egg into an animaP 8. Although not exactly 'catalysis' in the sense of Berzelius's theory, Mulder's conceptions were fully in line with what he believed to take place in contact actions 39. As during abiogenesis 'nothing' is added f r o m without, Mulder took the very nature of vitality to be a manifestation of such catalytic actions. Yet, as I have pointed out, Mulder did not think that the complex circumstances underlying m a n i f e s t a t i o n s of vitality m a y simply be denoted in physicochemical terms '°. Although combating the idea of a unique force operative in such actions, Mulder must not be called a materialist. His views were far more finely shaded than either a dogmatic vitalism or a dogmatic materialism. Liebig was a m o n g the last scientists who maintained the notion of vital force. Yet, he severely combated the abuse made of it by the Naturphilosophen: mit Lebenskraft, mit dynamisch, mit specifisch, mit Vauter in ihrem Munde sinnlosen Worten, die sie selbst nicht verstechen, erklaren sie Erscheinungen, die sie ebenfalls nicht verstehen. Die Lebenskraft der Naturphilosophie ist der Horror vacui, der Spiritus rector der Unwissenheit '1. H o w must we explain his own use of this notion in view of this statement? Liebig '2 defined the 'vital force' as 'the complex of causes of vital p h e n o m e n a ' and pointed out that its usage is analogous to that of the term 'affinity', which denotes the complex of causes of chemical phenomena, and of which we know nothing more than of the causes of vitality. So his definition was intended to be 'operational', it provided a mental s u m m a r y of a number of factors under ~rG. J. Mulder, Scheik. Ond. Utrecht 1 (1842), 539; Ibid. I! (1845), 409. 38G. J. Mulder, Aant. Prov. Utr. Gen. (1845), 41; Proeve etc., note 17, pp. 6 3 - 87. 3~E. Glas, Janus L X i l l (1976), 281 - 2 8 6 . '°G. J. Mulder, Proeve etc., note 17, pp. 408, 417-423. " J . Liebig in Reden und Abhandlungen, note 25, p. 23 (1844). ,2j. Liebig, Chemische Briefe, 4e Aufl. (Leipzig, Heidelberg, 1859); Brief XVI, pp. 2 4 2 - 2 4 3 , footnote.

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the heading of an unknown, yet allegedly common cause. Liebig's conception was not so different from Berzelius's. In the latter's view the 'catalytic force' is the as yet unknown, but allegedly common cause of the contact actions underlying manifestations of vitality. Both held that the force concerned is a manifestation of chemical force at a high level of organisation. But Berzelius identified chemical force with electric force, which Liebig considered an over-simplification. Liebig recognised that we do not know any more of the chemical force (affinity) than of the vital force. Chemical and vital force cannot even be clearly demarcated; indeed, he once even claimed that chemical actions are the only known causes of vitality4L I fail to see why T. O. L i p m a n " should have considered the above definition 'obscurely stated' and put so much emphasis on Liebig's vitalism. Although his usage of the term is not clearly derived from observational evidence,I think that Liebig did make sufficiently clear for what purpose the force had been defined. He reserved the designation 'chemical' for actions at an unorganised level and spoke of 'vital' when organisational aspects were more conspicuous. Although chemical affinity and vitality could not be clearly demarcated, the 'chemical' aspect of the vital force now could be conceived as just another 'mechanical' force, capable of interacting with the molecular forces operative in the living organism. The 'organisational' aspect makes it, in a way, a cause by its own operation, capable of overcoming chemical affinity at an unorganised (molecular) level. On combining the two aspects one has a 'force' whose mode of operation is 'mechanical' but nonetheless can direct its action in an autonomous fashion. In short: the vital force is defined exactly in such a

way as to justify the metaphysical guidelines applied in his physiologicalchemical methodology. The conception was metaphysical (in the sense explained before) and devised to cover the particular 'beliefs' applied in his lines of reasoning. Let us now briefly summarise these applications. In his theory of fermentation it is a force that protects the organic substances from decay by 'overcoming' their natural tendency to fall apart into simple, inorganic compounds. This justified his reasoning 'statically' on the basis of the balance between 'inertial capacity' and 'chemical instability' of organic molecules, the vital force accounting for the fact that fermentation takes place only when its influence is withdrawn. In his metabolic theories it is a force that impresses on the molecules of nutrition a special 'organisation', endowing them with 'vital' properties. Here it justified the discontinuity between the properties of molecules within and those outside the domain of life. ,3j. Liebig in Reden und Abhandlungen, note 25, p. 64, footnote (1844). " T . O. Lipman, Isis LXIU (1967), 182, 185; cf. G. J. Goodfield, The Growth of Scientific Physiology (London, 1960) chpt. 7.

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The conception enabled him to define his observational evidence 'statically', without accounting for chemical individuality, for the vital force is capable of overcoming the molecular forces operative in unorganised substances. It enabled him to reason along the lines of economy in tracing metabolic pathways, for the vital force acts autonomously owing to its 'organisational' aspect, so why not economically purposeful? Essentially, the system must be considered as an attempt at introducing Newtonianism into physiology, implying the 'operational' definition of the cause of a number of actions in order to make quantitative treatment possible. However, unlike a truly operationally defined force, it was from the outset conceived metaphysically. We now come to a more general analysis of the attitude displayed in Liebig's system of physiological chemistry. We shall contrast it with Mulder's. Determinism Still another aspect of Liebig's and Mulder's metaphysical positions may be reconstructed: their views on determinism. Determinism is always relative to some context, some theory '~. Classical particle mechanics, for example, is only deterministic with respect to the state variables defined by that very theory (position and momentum of particles), and nothing else (such as chemical states of the particles). Nineteenth century scientists such as Liebig, who aimed at causal theories in the context of the classical world picture, looked upon the state description of particle mechanics as the ideal point of departure. Liebig tried hard to establish physiological theories on such notions as 'impetus', 'inertia', 'force', 'amount of motion', etc. His faith in the universality and necessity of classical mechanics almost inevitably led him to the belief that vital phenomena, insofar as they exhibit mechanical traits, must fit into a deterministic causal theory based on the state description of classical particle mechanics. For Liebig the boundaries of causal explanation thus coincided with those of mechanistic explanation. This provides us with another indication about his usage and conception of the vital force. Liebig 'localised' the demarcation between vitality and 'mechanics' in this very notion: the force 'function' of the vital force enters into mechanistic theories, whereas the 'quality' of the vital force is considered irreducible. Vital phenomena, then, were liable to scientific (for Liebig: causal, mechanistic) explanation exactly insofar as they could be conceived in mechanical terms. 'Vitalism' and 'mechanism' were complementary rather than contradictory traits of Liebig's physiological thought. This mechanistic tendency of Liebig's lines of research and reasoning must be borne in mind when considering his attacks on Mulder's and Berzelius's alleged 'Aristotelianism ''6, i.e. the 'substantilisation' of properties into 'for"sCf. E. Nagel, The Structure o f Science, 4th impr. (London, 1974), pp. 2 7 8 - 2 9 3 . •6j. Liebig in Reden und Abhandlungen, note 25, pp. 6 5 - 66 (1844).

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mal causes'. The fact is that Liebig failed to recognise that explanations can be deterministic and causal without necessarily specifying the state of a system in the way of particle mechanics. Mulder, for example, pointed out that the tandem notions 'matter' and 'force' inflict themselves so vigorously upon us that we can hardly avoid looking upon phenomena in the context of these categories. But, on account of their aprioristic nature, these notions must not uncritically be identified with empirical concepts. 'Force', according to Mulder, is the 'cause of action'; it is absurd to posit forces in order to find causes 'r. Accordingly, Mulder did not aim at mechanistic model explanations but at finding lawlike descriptions. Explanations in terms of lawlike statements assume the form of conditionals rather than statements of 'efficient causality'. Liebig claimed that for an explanation to be adequate it had to be efficiently causal, starting from a state description which allowed, in principle, of complete specification. Only the state description of classical particle mechanics fulfilled this requirement. Mulder, on the other hand, held that such causal explanations ~vere altogether impossible in chemistry and physiology. 'Causes' (Ursachen) are 'primary things', not recognisable for the human intellect. We may only aim at finding laws by means of induction; a theory in terms of lawlike statements can be completely deterministic, even if it does not completely specify some initial state. For Mulder 'vitalism' and 'mechanism' were not complementary, as they were for Liebig. We cannot say in advance which aspects of life are, and which are not liable to scientific explanation. We just proceed from actions to conditions, whether the 'ultimate' conditions are fully specifiable or not.

Liebig's and Muider's Theories lmmunised So far I have tried to demonstrate that philosophical controversies, such as vitalism vs. mechanism, and rationalism vs. empiricism, if emerging in a scientific context, cannot rationally be analysed without referring to the methodologies in which they were conceived. These methodologies, in their turn, cannot be properly analysed, either, on their own ground, without referring to the scientific context in which they emerged. Theories can relatively easily be immunised against falsification. The notion of 'proteine', for example, initially denoted an isolated substance of which Mulder held that it occurs in all proteins, in combination with slight amounts of sulphur and phosphorus. As analyses became more accurate, several auxiliary hypotheses had to be framed to shield the 'proteine theory' against anomalies. Mulder now thought that proteine sometimes occurred in the form

4rCf. notes 18, 20.

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of a higher oxide of the same 'radical'. When, in 1847, it had been conclusively shown that proteine contains some sulphur itself (though not reacting in the regular way with lead salts), Mulder modified his theory in such a sense that proteine represented a hypothetical radical that could only be isolated in combination with some sulphur. Several auxiliary hypotheses were framed as explanations of the transformation of 'sulphide' sulphur (reacting with lead salts) into what Mulder now conceived as 'thiosulphate' sulphur (not so reacting). (Further details of this shielding strategy in a previous article) '8. A like strategy was elaborated by Liebig 49. In his theories of protein metabolism, e.g., he had claimed that proteins are always laid down in the tissues before being metabolised by the organism. When it had been experimentally demonstrated that proteins are oxidised in respiration, Liebig claimed that they are, upon transformation for the production of 'muscular' energy, split up into respirable substances. In his theory of fermentation, Liebig defined this as 'the communication of movement from the molecules of protein in decomposition to other substances'. After Pasteur had conclusively shown that fermentation is due to the life of micro-organisms, Liebig claimed that it is the internal movement of the proteins in those organisms which induces movements in the molecules in fermentation. Eventually Liebig claimed that fermentation and 'enzyme' action are 'communication of movement' without any further specification. Since in the context of the mechanist world picture (to which Liebig adhered) any event is essentially 'movement', Liebig's arguments - - highly circular from the outset - - had become altogether irrefutable, i.e. devoid of 'empirical' content. In much the same way Mulder had been forced to withdraw more and more of the falsifiable content of his theories. What remained were the methodological 'beliefs' as such. These were not discarded but carefully balanced and synthesised by Carl G. Lehmann in the methodological introduction to his influential textbook (1849-52) s°.

Lehmann's Methodological Considerations Lehmann considered Liebig and Mulder physiological chemists of equal skill and importance. He balanced their theories and methodologies in the context o f what he called 'true' Newtonianism 51. Let us see what he meant by this. In studying metabolism, hypotheses are indispensible, since sense perception alone cannot reveal causal relationships, the finding of which is nonetheless 'aE. Glas, Janus LXll (1975), 289. ~0j. Liebig, Ann. Chem. Pharm. CLIII (1870), 1, 137. ~°C. G. Lehmann, Lehrbuch derphysiologischen Chemie, 2e Aufl. (Leipzig, 1849-1852). S'lbid. Bd. I, p. 2.

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the true object of science. But a hypothesis is only valuable if justified by the phenomena, which distinguishes it from mere speculation. Physiological chemistry cannot be founded on mere elementary analysis of impure substances such as blood and bile. This kind of reasoning is arbitrary, as it is not guided by chemical experience. And it is not allowed to replenish a hypothesis by other hypotheses, which would entail an infinite regress. What kind of hypotheses does Lehmann refer to then? Obviously not the statistical calculations of Liebig. He did not reject, however, such arguments altogether, provided they be accompanied by a demonstration that the reactions assumed do actually occu:L In order legitimately to apply such calculations, various conditions must be fulfilled, and these are the very terms elaborated by Mulder: investigation into the morphological-anatomical aspects, into the chemical constitution (not merely the composition) of the substances, into their physiological functions and into the physiological and chemical characteristics of the fine structures of the tissues. Thus Lehmann recognised that research founded on the balances of elementary composition of the substances involved in physiological transformations is fully legitimate, provided that such an abstraction is guided by scientific criteria rather than by apriori metaphysical beliefs. Lehmann proposed a stepby-step procedure. Firstly, the chemical as well as the physiological status of the relevant substances is to be investigated. As to the proteins, doubtlessly the most relevant to physiology, Lehmann maintained Mulder's proteine theory 'des bessern Verst~mdnisses und der leichteren fAbersicht halber'SL After the chemical characterisation, the occurrence of the substances as well as their genesis and degradation are to be studied. Then the constitution of tissues and body fluids may be investigated. Again, no deductions must be made from analytical data, but experiments and microscopical observations must be undertaken. Only in the very last phase may the study of metabolism be taken up on the basis of the previous phases. But so long as these have not been sufficiently elaborated, the statistical method may be applied because it is the only quantitative method available, s' Here Lehmann made an allowance for Liebig's methodology in order to preserve the classical aims of science - - efficient causality and quantitative explanation - - which seemed barely possible in Mulder's methodology. Yet Lehmann's ideas about the potentiality of the statistical mode of reasoning were far more restricted than on Liebig's views. It can only teach us 'what' happens, not 'how' or 'why' it happens, which can only be investigated along s21bid, pp. 3 - 4. 5)Ibid. pp. 3 3 4 - 3 3 5 . s'Ibid, pp. 15 - 19.

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inductive lines. Lehmann's Newtonian ideals induced him to believe in the possibility of eventually settling on a mathematical formula,with exactness and certainty, in which all relevant parameters figure, but freilich sind es der Functionen sehr viele, die man in eine solche Formel wird aufnehmen m0ssen, und der Forschungen sind noch unzahliche erforderlich, ehe dieses Ziel erreicht werden kann .... s5 Thus Lehmann synthesised the two viewpoints by relativising their dogmatic purport and assigning to each of them a separate role in his own methodology: Mulder's as the inductive starting point and Liebig's as the rational context which, ultimately, the inductive line of reseach was to provide with material contents. Only their combination, Lehmann thought, would eventually lead to truly scientific theories of vitality.

Impact on Physiological Thought during the 1860's Central to Liebig's system of metabolism was his classification of nutrients into 'respiratory' and 'plastic' ones. This classification had been inspired by the (then) current opinion that animal heat is generated in the blood. Carbohydrates and fats were supposed to be, ultimately, dissolved in the blood where, upon oxidation, they liberate their heat of combustion as animal heat. To the proteins, on the other hand, was assigned the more complicated function of transforming chemical into contractive energy in the muscles. Liebig held that proteins are always first laid down in the tissues before being metabolised (if metabolised at all). It is of some importance to note that Liebig published his metabolic theory in 1842, 56 i.e. after the publication of Hess's law (1840), but prior to Joule's computation of the mechanical equivalent of heat (1843). He linked up with Lavoisier in calculating the heat derivable from respiration on the basis of the heats of combustion of the elements constituting the nutrients. For such calculations to be valuable, one has to presuppose that no forms of energy other than heat arise during the respiration of fats and carbohydrates, and that these substances are wholly oxidised rather than contributing to the growth of living substance. It has to be presupposed, moreover, that no other sources of animal heat exist, i.e. that proteins are not oxidised in respiration. It is obvious that the theory is largely presupposed in the definition of its observational evidence. This lack of falsifiable contents did not prevent it, however, from appealing strongly to the physiologists, who expected that it would revolutionise physiology. Owing to the discovery of the mechanical equivalent of heat Liebig's theories came under attack, but these attempted refutations proved very useful as means to singling out the ill-founded parts of

5nlbid. Bd. III, p. 449. ~6j. Liebig, Die organische Chemie in ihrer Anwendung auf Physiologic und Pathologie (Braunschweig, 1842).

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the argument and replacing them by sound thermochemical and thermodynamical principles. It was shown experimentally, for example, that proteins contribute to the generation of animal heat, and that protein degradation alone (as measured by the urea output of the organism) was insufficient to account for all the work performed by the organism. Leibig~r met these objections by replying to the first point that proteins, after having been partially degraded to yield contractive energy, are transformed into respirable substances, and to the second that the amount of protein degraded does not correspond to the work performed on account of the muscles being capable of storing potential energy. However, in order not to violate the law of energy conservation it had to be assumed that, in the long run, this equivalency should nevertheless obtain. This was definitively disproved by Voit and Pettenkofer. 58 Hence it appeared that all three groups of nutrients contribute to the production of both 'thermal' (respiratory) and 'mechanical' (contractive) energy. This caloric equivalence of the nutrients was denoted as 'isodynamy'. The basis of Liebig's system had now been refuted but meanwhile a fruitful doctrine of energy metabolism had been erected on that very basis. This had been possible thanks to the application of the successful partial reductions expressed in the law of energy conservation and the calculation of the mechanical heat equivalent. In France, Liebig's system was far less influential. Claude Bernard quoted Mulder while denouncing Liebig's statistical calculations. He himself developed an experimental physiology based on the techniques of vivisection. By 1853 he had discovered the 'glycogenic function' of the liver, the synthetic apparatus that converts glucose into animal starch. Bernard 59 thought that there is in the living organism a delicate dynamic equilibrium between 'organic degradation' and 'organised synthesis', maintaining a constant internal environment. Unlike Mulder, who rejected any apriori judgment about the demarcation of animate and inanimate processes, Bernard assumed a dogmatic standpoint inspired by the positivist philosophy of Auguste Comte, then widely influential in French science. The positivist view of physiology and chemistry is represented by E. Littr66° in particular on the theoretical, and by Robin and Verdeil 6' on the technical side. They hold that the 'proximate principles' are the starting point of chemical, and the ter-

57j. Liebig, Ann. Chem. Pharm. CLIli, (1870), 1, 137. s~C. Voit and M. Pettenkofer, Z. Biol. II (1866), 459; C. Voit, Z. Biol. Vi (1870), 303. ~9On Bernard's methodological views, cf. N. R o l l - Hansen, J. Hist. BioL IX (1976), 59. 8°E. Littr6, De la science de la vie clans ses rapports avec la chimie, 1855, in La science au point de vue philosophique (Paris, 1873), pp. 191 - 244. e'C. Robin and F. Verdeil, Trait~ de Chimie Anatomique et Physiologique Norrnale et Pathologique (Paris, 1853).

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mination point of biological analysis. Although the laws of chemistry do not cease to hold in the domain of life, the chemical phenomena in organisms are irreducible owing to the irreducibility of the laws of biology, dictating irreducible boundary conditions for chemical actions. It was largely in keeping with this trait that Bernard tended to overemphasise the antagonism between organic degradations and organised syntheses, the former taken as enzymatic chemical processes ('ph6nom6nes de mort'), the latter (e.g. the synthesis of glycogen in the liver) as irreducible physiological processes ('ph6nom6nes de vie'). Fermentation was almost designated apriori as a phenomenon of death? 2 For the purpose of this article it is not feasible to enter into the intricacies of Bernard's system. Suffices it to state that Bernard, like Mulder, elaborated a line of research tending to unveil lawful correlations. But unlike Mulder he defined apriori a line of demarcation between animate and inanimate processes, and between the domains of chemistry and biology. He thus tended to obstruct chemical elucidation of vital processes while assigning too hastily the label 'chemical' to other processes, such as fermentation and enzyme action. Against such dogmatic inclination Louis Pasteur entered the lists. 63 He combated Liebig's and Bernard's systems alike, reproaching the former with deceptive clarity and the latter with doctrinaire schematism. 6, Although possibly chemical in essence - - Pasteur even once spoke of fermentation as 'ph6nom6nes chimiques '6~ - - these actions differ fundamentally from ordinary chemical processes in that they often exhibit a vectorial nature (implying discrimination between optical isomers, unkown in ordinary chemistry). Moreover, the chemical and mechanistic theories of fermentation failed to account for the specificity with regard to the species of ferment as exhibited by the diversity of by- and end-products of fermentative processes. Further analysis of Pasteur's views would go beyond the scope of this paper. The essential point was that studying fermentation and enzyme action as chemical processes should be allowed only if guided by scientific arguments rather than dogmatic prejudice. And as the matter stood during that epoch. Pasteur thought, it seemed not yet feasible to undertake such an investigation in any justifiable way. Conclusions

About the middle of the nineteenth century attempts were made to apply the e'C. Bernard, Lecons sur les ph~nom#nes de la vie c o m m u n s aux ani m aux et aux v#g~taux, (Paris, 1878). S3L. Pasteur, Examen critique d'un 6crit posthume de Claude Bernard sur la fermentation, Paris, 1879, in Oeuvres complets, Tome II, (Paris, 1922). 8'H. Hein, J. Chem. Educ. XXXVIli (1961), 614. e~L. Pasteur, Oeuvres complets, note 63, Tome I1, p. 387.

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results of 'inorganic' science (elementary and proximate analysis) to the study o f vital phenomena. Lacking scientific guidelines, scientists were constrained to handle metaphysical arguments while confining aspects of vital actions to traits describable in the context of various levels of inorganic science, such as chemistry, physics and mechanics. Owing to their metaphysical implications the observational bases of these theories were not capable of making much contact with each other. The present article has mainly been concerned with the systems of Liebig and Mulder. These theories were continually modified to shield against accumulating anomalies. By 1860 they had developed into systems deprived almost completely of falsifiable content. Yet, they were not discarded, nor is it clear that they should have been. Falsificationism, as a device for theory appraisal, either in the Popperian or in the more sophisticated sense of Lakatos's rationality theory, does not seem appropriate to account for the developments outlined here. T o Liebig's and Mulder's German followers the two systems appeared not only as different modes of abstraction, but also as different levels of abstraction. The latter feature could serve as a basis for logical contact, since between two levels of abstraction partial reductions are possible, connecting statements of the less abstract with those of the more abstract. Once some such partial reductions have proved possible, they serve as scientific guidelines for abstraction, replacing the initially inevitable metaphysical arguments. So long as two systems have not proved completely mutually reducible, some metaphysical arguments continue to be involved, but, as the present article was intended to illustrate, such arguments are increasingly accounted for scientifically. As complete reductions are rather rare in science, in particular in biochemistry, some degree of immunity will possibly continue to stick to our conceptual systems. This does not have to prevent us, however, from directing our enterprise along scientific guidelines, based on the prospect or success of partial reduction. Only such reductions enable us to violate the immunity of our conceptual systems in whose context we look upon our objects of study. Reduction, as a violation of immunity, must involve an increase of content. This does not imply, however, that increase of falisifiable content must be handled as the sole methodological criterion for judging the potentialities of a line of research and argument. Formulating a number of phenomena in terms of some conceptual context need not be increasing falsifiable contents, but it is reductive, for any description in terms of some conceptual context is a reduction of the infinite class of all possible statements about sensual experiences with respect to some state of affairs. (The plenitude of reality is reduced to statements in that context.) Which among a number of such contexts is the 'best' depends on their opportunity for further (partial) reduction. At any particular time, preference for either of a number of approaches will, at least par-

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tially, be based on metaphysical arguments. Yet, as I have hoped to demonstrate, such arguments can be critically discussed in the light of the contemporary state of the science, i.e. the prospect or success of partial reduction (reduction in the sense explained at the outset, which is possible, as I have argued, because there is logical contact between conceptual contexts in respect o f their level of abstraction). On account of their metaphysical implications, all conceptual contexts are 'subjective', a way of looking at phenomena. But reduction destroys the immunity of such contexts and thus ensures that the use of metaphysics is now 'regulative' rather than 'dogmatic', it has no longer a life of its own but is employed only 'regulatively', as a guideline for research, relative to science and liable to scientific discussion in the light of the progress o f science. As I have tried to demonstrate, it was Lehmann who relativised the 'dogmatic' aspects of Mulder's and Liebig's methodologies and came to make a purely 'regulative' use of them by balancing them in the light of the contemporaneous state of the science. This was possible because he recognised that the degree of abstraction employed in the two theories provided a standard for bringing them into logical contact. The inevitable implication of metaphysical attitudes (often covert ideological thinking) that are part of the scientific enterprise defines this as a human activity, not independent of all other human activities. But, although scientific theories will always remain our human views of reality, w h a t we are ultimately dealing with is a reality independent of that view, implying a possibility of objectively successively improving our understanding.