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From Friedrich Wöhler’s Urine to Eduard Buchner’s Alcohol

These pages contain the full text of the following chapter: Herbert C. Friedmann (1997) From Friedrich Wöhler’s Urine to Eduard Buchner’s Alcohol, pp. 67–122 in New Beer in an Old Bottle: Eduard Buchner and the Growth of Biochemical Knowledge (ed. A. Cornish-Bowden), Universitat de València, Valencia, Spain. A PDF file (172 kilobytes) is also available.

The callidum innatum, the vital flame, or animal spirit in man, is supposed the cause of all motions in the several parts of his body... This pure spirit or invisible fire is ever ready to exert and shew itself in its effects..., cherishing, heating, fermenting, dissolving, shining, and operating, in various manners...

BISHOP BERKELEY (1744): Siris, sections 156, 157.

Where now the vital energy, that moved While summer was, the pure and subtle lymph Through the imperceptible meandering veins of leaf and flower?

WILLIAM COWPER (1784): The Task, Book VI, 134–137

I don’t know what you mean by glory Alice said. Humpty Dumpty smiled contemptuously. Of course you don’t — till I tell you. I meant there’s a nice knock-down argument for you!

But glory doesn’t mean a nice knock-down argument, Alice objected.

When I use a word, Humpty Dumpty said, in a rather scornful tone, it means just what I choose it to mean — neither more nor less.

The question is, said Alice, whether you can make words mean so many different things.

The question is, said Humpty Dumpty, which is to be master — that’s all.

LEWIS CARROLL, Through the Looking Glass

The words and phrases used by men and women throughout the ages are the loveliest flowers of humanity... the whole past from the time when the word was coined is crystallized in it; it represents not only clear ideas, but endless ambiguities.

GEORGE SARTON (1952) A History of Science, Preface

When people refer to non-enzymic reactions as being chemical they give the impression that the enzymic reaction does not belong to chemistry

DUILIO ARIGONI (1994)

A scientific discovery is both culmination and promise. It is a child of its times and a progenitor of the future. The greater the discovery, the greater the number of threads that it weaves together into a new fabric of coherence and understanding, the greater the tapestry of promise that it unfolds. Like a work of art we admire it, celebrate it in its own right. It has been said of Johann Sebastian Bach that he is a Janus, one of whose faces looks at the past, the other to the future (Cart, 1885). On 22 February 1828, Friedrich Wöhler, who had just shown that urea can be produced from ammonium cyanate, wrote a letter to his mentor, Jöns Jacob Berzelius in Stockholm:

I can no longer, as it were, hold back my chemical urine; and I have to let out that I can make urea without needing a kidney, whether of man or dog.

KEEN (1976); WALLACH (1901)

Both Wöhler and Buchner occupy Janus-like positions in the development of different branches of chemistry. We are here concerned with tracing the development of biological and what we now call biochemical ideas and experiments that led to Buchner’s accomplishment of cell-free fermentation. We must try to understand his work not only, as is usually done, as originating beam but also as gathering focus: the one clarifies the other. At the end of this article we will return to Friedrich Wöhler, for at that point an enquiry into divergencies and coalescences in the historical development of organic chemistry and of biochemistry will be extremely instructive. For the present, and for the bulk of this article, however, we must focus on topics of more narrowly defined biological interest.

The last quarter of the 18th century had witnessed a remarkable dissolution of ancient shackles expressed in terms such as anima, entelechy, soul, archeus, vital force that, in the words of Joseph Needham (1956; quoted by Teich, 1965)

dance processionally through the history of European thinking because a deus always had to be found for a machina.

Lavoisier (1777) had shown by quantitative measurements that the respiration of animals [and] combustion [are] operations... much more closely related than is obvious at first sight. The Abbot Lazzaro Spallanzani (1780), continuing work by René Antoine Ferchault, Sieur de Reaumur (1761), had found that gastric digestion is a chemical activity that can continue outside the organism: the living system was demonstrated not to be needed for the continuation of a biological function. These were experimental results whose insistence chipped away at an edifice of vitalist supposition that held earlier science in its thrall, but they only chipped away.

Our story continues with meanderings through intermeshing central threads of 19th century discovery and 19th century contention, each with its own antecedents, that occupied some of the greatest minds of 19th century science: fermentation, digestion, vital force, the development of organic chemistry, catalysis, enzymes. Among these, it is vital force that provides a recurring leitmotif that informs curiosity, inflames contention and serves as a convenient, ever available refuge of explanation. Vitalist ideas encompass a wide range of biological contention throughout the 19th century and into our own century. We will be concerned with the saga of a fencing match between vitalism and biochemical observation, where believers in vital force, driven ever more into regions of decreasing application, continue to maintain claims of validity in rearguard actions of persisting subtlety, while its opponents, fed more and more by chemical verification, dispel vital force insistence with ever more encompassing demonstrations of irrelevance.

Buchner’s discovery of cell-free fermentation modified perspectives and, in so doing, as always in good science, it raised major new issues that were, in turn, to capture the attention of some of the most eminent biochemists of the 20th century: metabolic pathways, controls, structural correlations at the molecular and cellular level, compartmentation, channelling, biochemical unity, eukaryotic compared with prokaryotic gene expression, and many more.

Let us begin with the remarkable thoughts of one Johann Christian Reil, clinical professor and director of the clinical institute at the University of Halle, who in 1795 founded the Archiv für die Physiologie, the first journal devoted exclusively to physiology. The very first article in volume 1 of that journal is entitled Von der Lebenskraft (About the Vital Force). What a topic, we would say, to begin a scientific journal! What a reflection of the scientific preoccupation of its times! But Reil had his own message. In this article he argues elegantly, mainly from logical considerations, that no vital force can exist, and that the phenomena of life can and should be explained in terms of chemistry. Reil was a famous physician — among his patients were Goethe and one of the brothers Grimm (Eulner, 1976; Wallach, 1901) —, a medical educator... and... innovator in psychiatric care (Risse, 1975). He is remembered by anatomists for the limiting sulcus of Reil and for the island of Reil. His article on the vital force still makes for fascinating reading. Space permits only a few excerpts:

Medical doctors and philosophers have always been inclined to deduce the phenomena of living nature... from ghosts... The ancients assumed nymphs in the trees, van Helmont an archeus, and Stahl a soul as principle of the appearance of living beings. However, experience gives no proof for the existence of ghosts... Must we deduce the magnetic property of iron as due to something else than matter since magnetic phenomena are not found associated with tin, stones or wood?... A special name is used for the formation of the substance of living beings, because of their remarkable perfection. Organ and organization hence is the formation and structure of living bodies. Linguistic usage and the derivation of the word organ teaches that the word organization refers to the formation of this substance. It follows that one has used the word organization metaphorically, i.e. one has named living beings, simply because of one of their properties, as organic beings... We have here a reason that so many errors and misunderstandings have crept in relation to the meaning of the word organization ... All phenomena in the world of bodies are results of a given form and mixture of matter... Force is something that cannot be separated from matter, it is a property of matter, and it is only through matter that it can be manifest... [We] would not need the concept of force, which leads to several erroneous consequences... I have used the term vital force for the force of matter that characterizes the plant and animal kingdom... Perhaps others will find the term organic force to be more suitable. However, I did not use this term since the word organization by common usage denotes the formation of living beings. Words... are arbitrary symbols of our concepts, and it... is important that the concept associated with a word be precisely ascertained... The physical, chemical and mechanical forces of animal bodies are, as one says, subordinated to the vital force... However, such a domination and subordination can actually not be accepted in nature... Our subjective concepts, which we import into nature, frequently dazzle the understanding of dumb people and provide them with a toy instead of with reality... If conditions change, then laws are changed not in nature but in our understanding... [Erasmus] Darwin is of the opinion that growth and the maintenance of living beings occurs not via chemical affinities, but via animal appetites. Every part, he says, has its own appetite... However, can one possibly think of an appetite without any supposition? If, indeed, we remove those suppositions from Darwin’s animal appetites, what remains? In fact nothing remains but chemical attraction, unless we wish to denote one thing with two types of words... [The] phenomena of [animal] bodies are activities and properties of their matter.

REIL (1795, my translation)

The term vital force was very widely used at the time: Joachim Dietrich Brandis (1762–1845) had written a book (published 1795) with the title Versuch über die Lebenskraft (Experiment concerning the Vital Force), reviewed by Reil in that first volume of his journal, while the Grundzüge der Lehre von der Lebenskraft (Fundamentals of the Teachings about the Vital Force) of Theodor Georg August Roose (1771– 1803) underwent two editions (1779, 1803) and a translation into Italian (1802). In 1794 Alexander von Humboldt used the term, and he is strongly attacked by Reil in the present essay, since Humboldt maintains that the vital force not only does away with the chemical bonds based on chemical affinities, but that it places other obstacles in the way of chemical reactions in living bodies. At the very same time (1795), Humboldt wrote a short story Die Lebenskraft oder der Rhodische Genius (The Vital Force or the Rhodian Genius), published by no less a person than Friedrich von Schiller in his short-lived monthly journal (1795–1797) Die Horen. Reil’s long paper, perhaps bolstered by the monumental experimental observations of the likes of Lavoisier, Reaumur and Spallanzani, made short shrift of speculation and would, from our perspective of 200 years later, have been expected to sound the death-knell of vitalist thought.

Yet this was not to be. Earlier ghosts returned with clinging insistence. It is possible that Reil’s work was rather too philosophical, and it has been stated, in contrast, that the clear data of Reaumur and Spallanzani were not accepted by the scientific world of the period (Effront, 1917, p. 15), perhaps because they are overwhelmingly experimental with almost no polemics and very few theoretical considerations (Bates, 1962, p. 360).

Fifteen years later (1810) we encounter an address Progress and Present State of Animal Chemistry given by the eminent chemist Jöns Jacob Berzelius on the occasion of the completion of his term as President of the Royal Academy of Sciences, Stockholm:

We can regard the whole animal body as a machine which gathers materials for ceaseless chemical processes out of the food that it receives,... but the cause of most of the phenomena in the animal body is so deeply hidden from our understanding that we will certainly never discover it. We call this hidden cause the vital force... The chain of our experiences must always end in something beyond understanding, but unfortunately this incomprehensible something plays the main role in animal chemistry and in this manner influences every process, even the smallest one. It follows that we can at the most learn about the nature of the products, while the manner in which these are formed must remain an eternal secret.

This address must have generated a great deal of interest, for within three years it had been published in English and in German (Berzelius, 1812; Simmer, 1955, p. 219; Rocke, 1992, p. 121).

Berzelius’s views on the inscrutable nature of living processes did not long remain unchallenged. In a direct attack, 1815, on Berzelius’s so-called zoochemistry, one of Reil’s students, Georg Karl Ludwig Sigwart, gives his own view of the content of zoochemistry. He emphasizes chemistry and, in contrast to Berzelius, completely ignores the vital force. He gives a definition of zoochemistry that would apply to large parts of modern biochemistry:

Animal organisms have chemical activities that depend on life and on organization. We use the term chemical life processes to denote these activities... [These] chemical activities of the living organisms, or the animal-chemical life process, constitute the topic of zoochemistry which studies (1) the products of these chemical life processes, and (2) modes of formation, the genesis, of these products from the perspective of [in Absicht auf] the chemical process.

SIGWART (1815), SIMMER (1955, my translation)