A history of research on yeasts 1: Work by chemists and biologists 1789–1850

Yeast 14, 1439–1451 (1998)

A History of Research on Yeasts 1: Work by Chemistsand Biologists 1789–1850

JAMES A. BARNETT*

School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, U.K.

— beginnings of yeast research; yeasts; history; Lavoisier; Cagniard-Latour; Kutzing; Schwann

The yeast, or fresh flowers of malt liquor, or wine, which are thrown up to the top whilst they arein the action of fermentation . . . if . . . mixed with other fermentable substances it wonderfullypromotes their fermentation, provided these flowers are fresh . . . called æõìç . . . a ferment . . . if thisleaven is mixed with fresh dough not yet fermented, it will make it ferment much sooner, and moreefficaciously than it wou’d do otherwise. Hence then we see, that a ferment may be soon preparedfrom a body in which no ferment actually existed before (Boerhaave, 173513).

CONTENTS

Introduction 1439Lavoisier’s analysis of fermentation 1439Studies of fermentation by Thenard andGay-Lussac 1441Influence of improvements in microscopy 1441Yeasts as living organisms: Cagniard-Latour,Kutzing and Schwann 1442Opposition from the chemical establishment:yeast as a physico-chemical phenomenon 1446Acceptance of yeast as a living organism bysome chemists and others 1448Acknowledgements 1448References 1449

INTRODUCTION

This is the first of a series of articles on the historyof research on yeasts which began at the end of theeighteenth century. During the period consideredhere, there were (a) the first major chemical analy-ses of ethanolic fermentation; (b) the conclusivedemonstration early in the nineteenth century thatyeasts are microbes and the cause of fermentation;(c) a remarkable attack on these microbiologicalfindings by some of the most influential scientistsof the time.

Previous relevant historical surveys, none ofwhich centres on yeasts, include those of Harden34,

Sciences, University of East Anglia, Norwich NR4 7TJ, UK.

CCC 0749–503X/98/161439–13 $17.50? 1998 John Wiley & Sons, Ltd.

Bulloch17, Partington52,53, Keilin37, Fruton30 andFlorkin28. Barnett has published a short reviewcovering the period 1789–present.6 In the currentseries, where practicable, evidence for statements isgiven and original material quoted, retaining theoriginal spellings.

*Correspondence to: J. A. Barnett, School of Biological

LAVOISIER’S ANALYSIS OFFERMENTATION

In his English dictionary36 of 1755, SamuelJohnson defined yeast as:

. . . the ferment put into drink to make itwork; and into bread, to lighten and swell it.

In the late eighteenth and early nineteenthcenturies, yeast was not considered to be a livingorganism. The first scientific research on yeast wasdone not by biologists but almost exclusivelyby chemists, who were investigating alcoholicfermentation. Indeed, the great Frenchman,A. L. Lavoisier, founder of modern chemistry,described the phenomenon of alcoholic fermenta-tion as ‘one of the most extraordinary in chemis-try’. In order to investigate, during fermentation,the conversion of sugar into carbon dioxide andalcohol, he carried out a number of analyses,estimating the proportions of the elements insugar, water and yeast paste. To ascertain whathappens during the production of wine, he set
about determining the composition of both the
Received 24 July 1998Accepted 25 July 1998

1440 . .

aCompose d’hydrogene & de carbone porte a l’etat d’oxide parune certaine proportion d’oxygene . . . la composition du sucresont a-peu-pres les suivantes.Hydrogene, 8parties

Oxygene, 64Carbone, 28Total, 100 (ref. 41, p. 142).
bLe suc des raisins, de doux & de sucre qu’il etoit, se changedans cette operation en une liqueur vineuse qui, lorsque lafermentation est complette, ne contient plus de sucre, & dont onpeut retirer par distillation une liqueur inflammable . . . adopterun nom . . . general; & celui d’alkool qui nous vient des arabes . . . (ref. 41, pp. 139–140).
? 1998 John Wiley & Sons, Ltd.

cle mout de raisin=acide carbonique+alkool. [Mout=must, i.e.

Table 1. Constituent elements of the materials and products of fermentation (percentageby weight, calculated from the results of Lavoisier, 1789).

Carbon Hydrogen Oxygen Nitrogen

Materials of fermentationCane sugar 28 8 64 —Dry yeast 31 7 42 19Water — 15 85 —

Materials yielded by fermentationCarbon dioxide 28 — 72 —Alcohol 29 17 54 —Acetic acid 24 8 68 —

fermentable substances and the products offermentation. As a result, in 1789, Lavoisier wasable to publish the first clear account of thechemical changes that occur in fermentation(Table 1). He found sugar to be:

. . . composed of hydrogen and charcoalbrought to the state of an oxide, by a certainproportion of oxygen . . . nearly 8 parts ofhydrogen, 64 parts of oxygen and 28 partsof charcoal by weight, forming 100 parts ofsugara

and wrote:41

When the fermentation is completed, the juiceof grapes is changed from being sweet, andfull of sugar, into a vinous liquor which nolonger contains any sugar, and from which weprocure, by distillation, an inflammable liquor. . . [for which] we have adopted . . . theArabic word alkohol . . .b

Lavoisier found that 100 parts by weight of sugarwere converted to 60·17 parts of alcohol, 36·81parts of carbon dioxide and 2·61 parts of acetic

acid. He also introduced the idea of the chemicalequation30,52, writing:

grape must=carbonic acid+alcohol.c

Lavoisier41 concluded that the effect of winefermentation upon sugar was merely to separate itselements into two parts, one part oxidized at theexpense of the other to form carbonic acid, whilstthe other part was reduced (deoxygene) to formalcohol. He did not say what caused fermentation,but showed it to be open to precise, quantitative,chemical analysis.

Despite having executed Lavoisier in 1794 (forhis role in collecting taxes under the previousregime, not for having laid the foundations ofmodern chemistry!), the new French republicangovernment gave considerable weight to the scien-tific understanding of alcoholic fermentation.Then, as now, wine and brandy were of majoreconomic importance in France, the world’sgreatest wine producer at that time. In 1823,the French had about 1·7 million hectares(1·7#1010 m2) of vineyards under cultivation,with an annual production of over 35 millionhectolitres (3·5#108 m3) of wine, valued then at£22·5 million.63 The wines were always subject toserious hazards of production, the biologicalnature of which was then completely mysterious;for example, the wine might turn into vinegar(by the action of acetic acid bacteria, as nowunderstood) or acquire a bad flavour (sometimesfrom the activities of the SO2-resistant yeast,Saccharomycodes ludwigii). So, in 1803, the eighthyear of the first French Republic, the Premiere

unfermented grape juice] (ref. 41, p. 141).

Yeast 14, 1439–1451 (1998)

1441 1789–1850

Classe (mathematical and physical sciences) of theInstitut de France, which had been founded in1795, offered a medal worth one kilogram of goldfor an answer to the following question:

What are the characteristics which dis-tinguish vegetable and animal substancesacting as ferments from those that undergofermentation?d

However, no satisfactory answers were submitted.The prize was therefore offered again in 1805, butlater withdrawn when the Institut became unable

22

try at the St.-Cyr Military Academy. Up till 1827,virtually all the research on fermentation hadbeen done by chemists, the first contribution of agenuine biologist to the study of yeasts beingprobably that of Desmazieres.24 He examined theorganisms of beer with a microscope, publisheddrawings and named the microbes in beer Myco-derma cervisiae (cervisia, cervesia or cerevisia areLatin words for beerg), and those of wine, Myco-derma vini. Some of Desmazieres’ drawings looklike yeast cells, and he recognized them as simpleliving organisms, but did not attribute fermenta-tive activity to them. By this time, microscopes hadbeen greatly improved. Aspects of these improve-ments were discussed by Amici1 in 1820 andLister44 in 1830. Amici made some of the firstmicroscope objectives to be corrected effectivelyfor chromatic and spherical aberrations. These

STUDIES OF FERMENTATION BYTHENARD AND GAY-LUSSAC

In 1803, L. J. Thenard, professor of chemistry atthe Eucole Polytechnique in Paris and colleague ofthe great chemist, J. L. Gay-Lussac, publishedstudies of fermentation, that were probably carriedout in response to the prospect of the Institut’sprize. Thenard72 drew attention to a depositresembling brewer’s yeast, produced by allfermenting liquids, and showed such deposits tocontain nitrogen compounds which, on distil-lation, produced ammonia. In 1810, Gay-Lussachimself31 made a further contribution. Using amethod described by Appert3 in the same year,Gay-Lussac brought closed bottles of grape juiceto the temperature of boiling water, kept themat that temperature for some time and then leftthem for a year without opening them. Once thebottles were opened, the juice began to ferment.Gay-Lussac concluded that oxygen reacted withthe juice, forming a soluble ferment which initiatedthe fermentation of grape juice. Heat inactivatedboth this ferment and the insoluble beer yeast.Later, after developing improved analyticalmethods with Thenard,30,53 Gay-Lussac (1810)32

revised Lavoisier’s figures, estimating that, duringfermentation, of 100 parts of sugar, 51·34 wereconverted into alcohol and 48·66 into carbondioxide.

The overall equation for alcoholic fermentation

C6H12O6]2 C2H5OH+2 CO2

is commonly attributed to Gay-Lussac, in particu-lar to his paper of 1815, for example by Nord and

pp. 206–207).


Weiss (1958),51 but also by many other authors inmore recent publications. However, the empiricalformula for glucose was in fact established byDumas25 only in 1843, and the molecular formulawas first published by Baeyer4 and Fittig27 in1870 and 1871, respectively, (see refs 56 and 57)e,Gay-Lussac having died in 1850.

dQuels sont les caracteres qui distinguent, dans les matieresvegetales et animales, celles qui servent de ferment decelles auxquelles elles font subir la fermentation (ref. 22,

eF. W. Lichtenthaler has drawn the author’s attention to thepossibility that one of the formulae given by Loschmidt(1861)46 might be the first published structural formula ofglucose. According to Beilstein’s Handbuch der OrganischenChemie, 31, Springer, Berlin (1938), p. 83, the structuralformula for glucose was given first by Fittig, R. (1869). U}berdie Constitution der sogenannten Kohlenhydrate, Zeitschriftfur Chemie, 22, 266; however, the author has not traced thispaper; see the bibliography of Fittig’s works in Berichte derDeutschen Chemischen Gesellschaft, 44, 1383–1401 (1911).
fLes levures sont donc formees dans l’acte de la fermentation(ref. 23, p. 141). ge.g. Pliny, Natural History, Book 22, LXXXII: Ex iisdem fiuntet potus, zythum in Aegypto, caelia et cerea in Hispania,cervesia et plura in Gallia aliisque provinciis . . . (Loeb Edition,
to pay.

INFLUENCE OF IMPROVEMENTS INMICROSCOPY

In 1825, J. J. Colin23 confirmed Thenard’s obser-vation of a deposit formed during fermentation.He wrote:

. . . the yeasts are thus formed in the act offermentation.f

Yeast, he said, promotes fermentation of sugarin the absence of oxygen. Colin had studied inGay-Lussac’s group and was professor of chemis-

edited by W. H. S. Jones, 1961, Heinemann, London).

Yeast 14, 1439–1451 (1998)

question put by the Institut de France. In doing so,they established yeast as a living organism. Thethree were Charles Cagniard-Latour, a physicistand engineer, Friedrich Traugott Kutzing, analgologist from Halle, and Theodor Schwann, thegreat physiologist of Berlin (Fig. 1).

In 1836, with a microscope that gave a magnifi-cation of 500 diameters, and also with anothermade by Amici,22 Cagniard-Latouri made obser-vations18,19 on the yeasts of beer and wine. Hedescribed them as composed of globules, which heconsidered:

. . . to be organized beings, which areprobably of the vegetable kingdom . . .

since they were not motilej and were formed by theenlargement of other globules.k Further, he made aremarkably accurate estimate of the diameter ofthe yeast cells as about 7 ìm.l As further evidencethat yeast was a living organism, Cagniard-Latour20 also drew attention to the increase in theamount of yeast during the fermentation of beerwort and emphasized this observationm in a later

1442 . .

hChercher a savoir lequel de ces trois savants est arrive lepremier a decouvrir l’organisation et la vegetation des Levures,nous paraıt une chose trop peu importante en elle-meme pourque nous nous y arretions un moment . . . Il nous suffit desavoir, et nous en avons la conscience, que ces trois experimen-tateurs, sans se connaıtre, sont arrives au meme resultat (ref. 76,pp. 394–395).
iCharles Cagniard de La Tour published under the name of Cagniard-Latour (see ref. 33).

j. . . on peut les considerer comme des etres organises, lesquelssont probablement du regne vegetal, puisqu’on ne leur voit pasexecuter de mouvements locomotifs (ref. 18).
k. . . les globules se sont formes par le grossissement des grainsprimitifs (ref. 19, p. 224). l. . . ces globules etant fort petits, puisque le diametre de ceuxqui paraissent avoir atteint le maximum de leur developpementn’est guere que d’un 150e, de millimetre environ . . (ref. 18). mLes globules du ferment sont susceptibles, a ce qu’il paraıt, depouvoir se developper tres promptement; car un peu de mout dela cuvee dont j’ai parle il y a peu d’instans, ayant ete examineau microscope huit heures apres la mise en levain, presentaitdeja dans le champ de l’instrument arme d’un grossissement detrois cents fois, quatre-vingts a cent globules, tandis qu’aussitotapres l’introduction du levain on n’en voyait moyennement que
corrections gave a greater numerical aperture and,hence, better resolution for magnifications of up to600 diameters.16,75,79 One of Amici’s microscopes,made in 1837, had a maximum numerical apertureof 0·54 and a resolution of about 1 ìm.79 Keilin37

has drawn attention to comments by Mandl,65

published in 1838 that, up to that time, microscopyhad been a dubious business:

. . . towards the end of the last century, themicroscope experienced the fate of so manyother new things; having exaggerated its use-fulness and used it to support lunatic flightsof fancy, people went to the other extremeand exaggerated its inconveniences andhazards; then its use was almost completelyneglected, and results obtained with it wereonly spoken of with mistrust. Even the exist-ence of blood corpuscles was doubted, andwhat Leeuwenhoek and his successors haddescribed were attributed to optical illusions(translated from the French).

YEASTS AS LIVING ORGANISMS:CAGNIARD-LATOUR, KU}TZING ANDSCHWANN

Largely as a result of the improvements in micro-scopes, between 1836 and 1838 three independentpioneersh went a long way towards answering the Figure 1. Portrait of Theodor Schwann, from Fredericq.29

dix-huit (ref. 22, p. 213).

Yeast 14, 1439–1451 (1998)

paper.22 He gave one of the first descriptions ofyeast budding20 and the first description of budscars. When he pressed the yeast between glasssheets, he saw oval marks or scars.n Later heelaborated on his observation of scars,22 andstated that the yeast globules parted from eachother as they grew older, leaving a scar (unecicatricule ou marque ombilicale). Remarkably, hisdescription of bud scars was ignored until, in 1950,they were rediscovered by Barton8 who observedthem in fixed and stained cells of Saccharomycescerevisiae.

In 1837, Cagniard-Latour21 summarized hisfindings as follows: (1) beer yeast is a mass of smallglobular bodies which, because they can reproducethemselves, are living (organises) and not, as hadbeen supposed, an inert or purely chemical sub-stance; (2) these bodies appear to be part of thevegetable kingdom; (3) they seem to break downsugar only when they are living; from which itfollows that it is probably by some effect of theirvegetable character that they liberate carbonic acidfrom this breakdown and convert the sugar intoa spirituous liquor. Cagniard-Latour added thatyeast, considered as living matter (une matiereorganisee), perhaps merited the attention ofphysiologists.

In the same year, F. T. Kutzing,40 the secondof the three pioneers, using a microscope madein Schiek’s Berlin workshop (Fig. 2) that gavea #420 linear magnification, published cleardescriptions and drawings of yeast cells. LikeCagniard-Latour, he estimated the diametersof the cells (Kugelchen) at about 6–9 ìm.o Hissuggestion that different kinds of fermentationwere due to different organisms was confirmed aquarter of a century later, in the 1860s, by LouisPasteur.

Theodor Schwann was the third and most illus-trious of these pioneer scientists. His experimentson fermentation68 were a sequel to his previouswork67 refuting the concept of spontaneousgeneration (generatio aequivoca). He filled fourflasks with a solution of cane sugar mixed withbeer yeast, stoppered the flasks, put them in boil-ing water for about 10 min and allowed them to

cool while inverted under mercury. A volume ofair, of between one-third and one-quarter of thatof the liquid, was next admitted to the flasks. Theair for two of the flasks, was first passed through athin, red-hot, glass tube (Fig. 3); analysis showedthat this air still contained 19·4% oxygen. Theflasks were re-stoppered and incubated at between13)C and 18)C (10–14)R). After 4–6 weeks ofincubation, fermentation began in the two flaskswhich had received unheated air, but not in theother flasks. Schwann concluded:

1443 1789–1850

n. . . il a remarque aussi sur plusieurs globules presses ainsi unetache ovale ou espece de cicatricule, ce qui lui semble encorefavorable a l’hypothese que les globules du ferment peuvent seformer par le prolongement d’autres globules (ref. 20).

Thus, in wine fermentation, as in putrefac-tion, it is not the oxygen of the air thatcauses fermentation to occur, but a substance,

o. . . im Durchschnitt betragt ihr Durchmesser 1/300***, bei dengrossern 1/250***, bei den kleinern 1/350*** (ref. 40, p. 387). (Thesymbol *** represents the unit of measurement called a Paris line,
which equals 2·255 mm (see refs 9 and 58).

Figure 2. A microscope of F. W. Schiek at Berlin, Halle’scheStr. 15, copied from Quekett.58 The pillar (A) is of brass onthree feet (B, C, D), with a cradle joint (E), to which is attacheda steel bar (F). Upon this, slides the support (G I) of the tube(K) and that of the stage (N). H is the coarse adjustment and Lthe fine adjustment; O is the mirror.

Yeast 14, 1439–1451 (1998)

contained in the atmospheric air, destroyed byheat.p

Schwann examined beer yeast microscopically andsaw the cells (Kornchen), most of which were roundor oval. Some were single and others were inchains of up to eight or more. The last one of achain was small and sometimes lengthened.

In brief, the whole resembles many articulatedfungi and is without doubt a plant.q

He found no yeast-like bodies in fresh grapejuice; but, when the juice was kept at about 25)C,yeasts appeared. He watched their growth andthe subsequent formation of bubbles of carbondioxide:

Only several hours later is it possible toobserve the development of gas bubbles,because at first the carbon dioxide dissolves inthe water.r

Schwann concluded that yeast cells grow bybudding; that sugar is food for yeast; that ethanol

elements not so used are preferentiallyconverted to alcohols

When engaged on this work, Schwann consulteda mycologist, F. J. F. Meyen, who concurred withthese conclusions. Schwann had called the yeast‘Zuckerpilz’, so Meyen introduced the genericname Saccharomyces,t with its species S. cerevisiae,S. pomorum and S. vini.48 Later, in MikroskopischeUntersuchungen69,70 where Schwann gave hisepoch-making evidence of the cellular nature ofplantsu and animals and where the term ‘meta-bolic’ was first used,v he reiterated many of hisearlier observations and conclusions on yeasts asliving organisms and their role in fermentation. He

1444 . .

pEs ist also auch bei der Weingahrung wie bei der Faulniss nichtder Sauerstoff, wenigstens nicht allein der Sauerstoff der atmos-pharischen Luft, welcher dieselbe veranlasst, sondern ein in deratmospharischen Luft enthaltener, durch Hitze zerstorbarerStoff (ref. 68, p. 189).
qKurz das Ganze hat grosse Aehnlichkeit mit manchengegliederten Pilzen, und ist ohne Zweifel eine Pflanze (ref. 68,pp. 189–190). rErst einige Stunden spater, als man die ersten dieser Pflanzenbeobachtet, zeigt sich die Gasentwicklung, weil die ersteKohlensaure im Wasser aufgelost bleibt (ref. 68, p. 190). (Thisis a remarkably early recognition of a problem that hasbedevilled yeast taxonomists’ fermentation tests, to which problem Kreger-van Rij (ref. 39) drew attention in 1962.)

sDer Zusammenhang zwischen der Weingahrung und derEntwicklung des Zuckerpilzes ist also nicht zu verkennen,und es ist hochst wahrscheinlich, dass letzterer durch seineEntwicklung die Erscheinungen der Gahrung veranlasst. Daaber zur Gahrung, ausser dem Zucker, ein stickstoffhaltigerKorper nothwendig ist, so scheint es, dass dieser ebenfalls eineBedingung zum Leben jener Pflanze ist, wie es denn an und fursich schon wahrscheinlich ist, dass jener Pilz Stickstoff enthalt.Die Weingahrung wird man sich demnach so vorstellen mussen,als diejenige Zersetzung, welche dadurch hervorgebracht wird,dass der Zuckerpilz dem Zucker und einem stickstoffhaltigenKorper die zu seiner Ernahrung und zu seinem Wachsthumnothwendigen Stoffe entzieht, wobei die nicht in die Pflanzeubergehenden Elemente dieser Korper (wahrscheinlich untermehren andern Stoffen) vorzugsweise sich zu Alkoholverbinden (ref. 68, p. 192).
tSaccharomyces is modern Latin, from the Greek óáê÷áñï-ísugar+µõêçò mushroom. uIn this work, Schwann collaborated with Jakob Schleiden,professor of botany at Jena, who supported Carl Zeiss’s appli-cation to establish the workshop where he made his firstmicroscopes (ref. 26). v. . . diese kann Man metabolische Erscheinungen nennen(ôï µåôáâïëé÷ïí was Umwandlung hervorzubringen oder zu
is excreted; and that nitrogenous substances arealso required by yeast. His conclusions68 wereunequivocal, revolutionary and correct:

The connection between wine fermentationand the development of the sugar fungus isnot to be underestimated; it is very probablethat, by means of the development of thefungus, fermentation is started. Since, how-ever, in addition to sugar, a nitrogenous com-pound is necessary for fermentation, it seemsthat such a compound is also necessary for thelife of this plant, as probably every funguscontains nitrogen. Wine fermentation mustbe a decomposition that occurs when thesugar-fungus uses sugar and nitrogenoussubstances for growth, during which, those

Figure 3. Schwann’s experimental set-up68 for supplyingheated air to a solution of cane sugar mixed with beer yeast, thesolution and yeast having been first heated to about 100)C.Illustration from Loffler (1887).45

erleiden geneigt ist) (ref. 69, p. 229).

Yeast 14, 1439–1451 (1998)

filtered grape juice began fermenting after threedays at 20)C; and he described clearly the micro-scopical appearance of the yeast globules as well asthe formation of buds.z In addition, he studied the effects of tannin, some inorganic salts and various

solvents on yeast fermentation.Turpin was a distinguished botanical illus-

trator. He not only added76 to Quevenne’s con-firmation of the findings of Cagniard-Latour,Kutzing and Schwann but, two years later healso published77 excellent and detailed drawingsof beer yeast (Fig. 4), which he called Torula

1445 1789–1850

wIhre Form ist die der Pilze, ihre Struktur ist, wie die der Pilze,da sie aus Zellen bestehn, von denen viele wieder junge Zellenenthalten, sie wachsen wie Pilze durch Hervortreibung neuerZellen an ihren Enden, sie pflanzen sich fort wie Pilze,theils durch Lostrennung der einzelnen Zellen, theils durchErzeugung neuer Zellen in den vorhandenen Zellen undZerplatzen dieser Mutterzellen (ref. 69, p. 235).

cervisiae.aa In October 1837, he spent a long andcold nocturnal seance at the great brewery of the

xLater drawn as Torula diabetica by Quekett (ref. 59, p. 18)‘constantly present during the fermentation of diabetic urine’.

Luxembourg:

. . . in order to follow, study, describe anddraw with the aid of the microscope, all the

yLa propriete la plus remarquable de ce depot, celle qui, jointea l’aspect microscopique, le caracterise d’une maniere precise,est celle de produire la transformation du sucre en alcool et enacide carbonique, quand on le met en contact avec l’eau sucreea une temperature convenable (ref. 60, p. 269).
phases of development of these little plants
producing the cells constituting the yeast of
zCes globules . . . paraissent circonscrits par un cercle noirmince . . . On en voit un certain nombre qui portent sur unde leurs cotes un globule plus petit, faisant corps avec lepremier. Le cercle noir . . . est interrompu au point de jonction,comme si le petit globule etait sorti du premier (ref. 60, pp. 268–269).

aaThe genus Torula was introduced by Persoon (ref. 55, p. 25);the Latin word torus, or torum, refers to a round, swelling, or

still held yeast cells to be those of fungi, for theygrew like fungi by forming new cells at theirextremities. In a footnote, he described theirpropagation, (a) by separation of distinct cells and(b) by generating, within cells already present, newcells that were liberated by bursting of the parentcells.w Probably this was the first recorded obser-vation of ascospores in a yeast. Schwann held thatyeast cells caused fermentation, because fermenta-tion was constantly associated with yeast propaga-tion and failed when the yeast was destroyed byheat. In addition, he commented that the yeastitself also increased during fermentation asColin23 had already observed, and that this kindof phenomenon was displayed only by livingorganisms.

The findings of the three pioneers were con-firmed almost immediately by two Frenchmen,Quevenne60,61 and Turpin.76 Turpin had beenasked by the Academie Royale des Sciences toassess the validity of Cagniard-Latour’s conclu-sions. Quevenne, who was trained in pharmacyand later worked on the characteristics of milk,found that deposits which formed in diabeticurine62 had the properties of an energetic fermentx

and likened them to deposits that were found inthe alcoholic fermentation of various substances.He made the unequivocal statement that the ‘de-posit’ causes sugar fermentation,y pointing outthat yeast taken from fermenting beer wort is,itself, highly fermentative. Quevenne also found

Figure 4. Engraving of a drawing of beer yeast by Turpin77

(he did not say whether he used a camera lucida, a device formaking accurate drawings of microscopic objects, invented,according to Quekett58 by W. H. Wollaston in 1807).

bulging place, or protuberance.

Yeast 14, 1439–1451 (1998)

1446 . .

bb. . . afin de pouvoir suivre, etudier, decrire et dessiner a l’aidedu microscope, toutes les phases du developpement des petitsvegetaux provenant des seminules composant la Levure debiere, pendant toute la duree de la fermentation d’une cuvee(ref. 76, p. 377; ref. 77, p. 109).
ccGeorges Oberhaeuser was spelt in this way by Turpin (refs 76 and 77), but Oberhauser by Quekett (ref. 58).

dddie Lust am Laboriren verliert sich spater, wir haben genuglaborirt, und ich bin es ungeheuer mude (in a letter from JustusLiebig to Friedrich Wohler, Giessen, 17 April 1841) (ref. 35,

buds enlarge to the size of their mother-cells. Hismeasurements of the cells correspond closely withthose made by Cagniard-Latour and Kutzing.Turpin’s experiments included adding beer yeast toa jar of water and sugar kept for a few days at25)C: after two days, he observed lively fermen-tation and budding of the yeast globules; but,after five days, fermentation ceased and the yeastglobules disintegrated and putrified, presumablybecause of bacterial contamination.

OPPOSITION FROM THE CHEMICALESTABLISHMENT: YEAST AS APHYSICO-CHEMICAL PHENOMENON

A remarkable event in the history of science wasthe strident denunciation of the concept of yeast asa living organism by three of the leading chemistsof the day, F. Wohler, J. von Liebig and J. J.Berzelius. In 1839, they took the following views,strikingly similar to those Georg Ernst Stahl71

had published in 1697 (Stahl, professor at theUniversity of Halle, had been a leading exponentof the phlogiston theory of combustion): (a) theagent which produces fermentation is formed asthe result of the action of air on plant juices whichcontain sugar; (b) decomposition of the sugaroccurs because of instability transferred to it by theunstable ferment; the latter is not a substance but acarrier of activity; (c) yeast is a decomposing bodywith molecules in movement (see ref. 81). It is oddthat these important scientists gave an account ofyeast which, today, seems less valid than that givennearly a century before in Johnson’s dictionary.Since von Liebig, the distinguished Germanchemist who held a chair at Giessen, was one of themost influential of all contemporary scientists,his vigorous campaign probably held back the

Figure 5. A microscope of Oberhauser of Paris, copied fromQuekett.58 He describes it as having a circular base of 10 cmdiameter, loaded with lead; the stage rests on a stout tube, 5 cmhigh, that is fitted on the base. The opening in this tube,enabling light to reach the mirror, can be seen in the figure; thetube can be turned on the foot and the stage on the tube. Thereare rack and pinion for coarse and a screw for fine adjustments.

beer, during the whole duration of thefermentation of the mash tun.bb

Using a microscope that gave a magnification ofup to 300 diameters, made by Trecourt andOberhaeusercc of Paris (Fig. 5), Turpin gave a clearaccount of budding, in which he described how the

development of microbiology for about 20 years.He made the telling admission in 184135 of havingalready tired of laboratory workdd when at the ageof only 37. No one with such an attitude should beallowed to influence the direction of research!

Von Liebig and Wohler, professor of chemistryat Gottingen, went so far as to publish in theirjournal, Annalen der Pharmacie, an anonymousskit,2 mocking the microscopical findings theyrejected. The skit, entitled ‘The riddle of alcoholicfermentation solved’, described yeast under the

p. 178).

Yeast 14, 1439–1451 (1998)

microscope as a tiny animal, shaped like a distil-ling apparatus, swallowing sugar and excretingalcohol from an anus and carbonic acid from itsgenitals.

In 1839, too, Berzelius of Stockholm alsostated11 that microscopical evidence was of novalue and that yeast was no more an organismthan was precipitate of alumina. Schwann’s con-trols, he wrote, were inadequate; his experimentswere worthless; and his conclusions exhibited afrivolity which had long been banished fromscience.ee Fermentation, he said, occurred bymeans of catalysis.

The hostility of these chemists may have come,at least in part, from their own and other chemists’considerable achievements in establishing organicchemistry as a science. As late as the early nine-teenth century, it was generally held that sub-stances, such as fats and sugars, associated solelywith plants and animals, could be formed only byliving things. But soon the chemists themselves didmuch to overthrow this belief. Wohler (1828b)84

himself, was responsible for one of the earliestproductions of an organic compound by chemicalmeans, namely that of urea from ammoniumcyanate. Appropriately, it was to Berzelius, whoseems to have been the first to use the expression‘organic chemistry’ in print,ff that Wohler (1828a)wrote triumphantly:83

I can make urea without the necessity of akidney, or even of an animal.gg

Moreover, at this time, various chemists hadbegun to make preparations that had enzymicactivity. Among the earliest were Payen andPersoz,54 who treated malt extract with alcohol toobtain a water-soluble white precipitate: this,reprecipitated with alcohol, rapidly made starchquite soluble. They called their preparation‘diastase’. Following the work of Robiquet andBoutron-Charlard,64 Wohler and von Liebig85

prepared ‘emulsin’ from bitter almonds (Prunus

amygdalus var. amara). Very little of this water-soluble powder was needed to hydrolyse theglycoside, amygdalin:

amygdalin]glucose +benzaldehyde+HCN

This activity was compared by Wohler and vonLiebig to fermentation:

to which Berzelius [they wrote] has attributeda peculiar, catalytic force . . . the com-paratively small amount of emulsin requiredfor decomposing amygdalin, shows that this isnot an ordinary chemical action; it hassome resemblance to the action of yeast onsugar . . .85

Some recent writers17,37,38 have held that vonLiebig and his chemist colleagues considered thatthe publications on fermentation by Cagniard-Latour, Kutzing and Schwann were reactionaryand a blow against the idea that processes associ-ated with living things were chemical ones. How-ever, others42,43,47 have drawn attention to thechemists’ continued adherence to the concept of a‘vital force’ (Lebenskraft82) (see also ref. 7).

Von Liebig’s passionate feelings were clearlyexpressed in a 44-page article81 on fermentation,putrefaction and decay and their causes, publishedin 1839. Here he made the following dogmaticassertions. Putrefaction consisted of a decay inwhich the oxygen of the air took no part and alsoan oxidation, of one or more elements of thedecaying substance, using the oxygen of that sub-stance or of water, or both. Fermentation wasputrefaction of vegetable material. The fermentitself (a) arose during a metamorphosis whichbegan after the entrance of air into a plant juicewhich contained sugar; (b) could continue withoutair; (c) did not cause fermentation; (d) was asubstance undergoing putrefaction or decay. Whenbeer or wine yeast was washed, the residue did notcause fermentation in sugar water. Although theresidue could be seen as globules under a micro-scope, the globules were not living, for theyoccurred in many non-crystalline substances. Tosummarize von Liebig’s view: the ferment isformed as the result of action of air on plantjuices which contain sugar; and decomposition ofthe sugar is owing to its instability conferred onit by the unstable ferment. Von Liebig seems to

1447 1789–1850

eeAus demselben Grunde sollte man auch schliessenkonnen, dass alle nicht krystallinischen Niederschlage vonThonerde, . . . und die unendliche Menge von unorganischenStoffen, die aus Kugelchen zusammengruppirte Faden bilden,die theils gerade, theils in einem Ring gebogen, theils aufverschiedene Weise zusammengelegte Streifen sind, Fadenpilzewaren. Eine solche Leichtfertigkeit in den Schlussen ist schonseit lange aus den Naturwissenschaften verbannt worden(ref. 11, pp. 400–401).
have done little, if any, experimental investiga- ffOrganisk Kemi (ref. 10, e.g. p. 6).
tion of fermentation to justify his grandiosepronouncements.

gg. . . dass ich Harnstoff machen kann, ohne dazu Nieren oder
uberhaupt ein Thier . . .
? 1998 John Wiley & Sons, Ltd. Yeast 14, 1439–1451 (1998)

this complex composition to be evidence of yeast’s

Kutzing.

1448 . .

ACCEPTANCE OF YEAST AS A LIVINGORGANISM BY SOME CHEMISTS ANDOTHERS

Nonetheless, some other important scientists ofthe 1840s and 1850s, even certain chemists,accepted that yeast was a kind of plant. One ofthese scientists was Eilhard Mitscherlich, who hadbegun as a student of oriental languages. He hadworked with Berzelius in Stockholm, became aprofessor of chemistry in Berlin and was the dis-coverer of isomorphism.49 In 1841 Mitscherlichshowed that the globules of yeast were so largethat they would not pass through a fine parchmentfilter. With a suspension of yeast in a glass tube,closed at the bottom by the filter-paper (Fig. 6), heput the tube into a sugar solution. The sugarpassed through the filter and was fermented, butno fermentation occurred outside the tube, wherethere was no yeast.50 Although he considered yeastto be a microbe, Mitscherlich explained the roleof the yeast solely in terms of contact catalysis ofthe yeast’s surface, as Berzelius had proposedearlier.

Another distinguished contemporary whoconcerned himself with the nature of yeast was


biological nature. Quekett, who was a micro-scopist and human anatomist, described59 Torulacerevisiae as a ‘yeast plant’. In his major work onwine and beer fermentation of 1845, Balling5

treated yeast as a living organism.hh

A biochemist of the present era has commentedon the work that has been described here:

It was through the study of alcoholic fermen-tation that the function of enzymes of cellmetabolism was generally accepted afterthe long controversy which started with thediscovery of the living nature of yeastby Cagniard-Latour, by Schwann and by

30

hh. . . so durfte an der vegetabilischen Natur der Hefe nichtmehr gezweifelt werden; denn dann konnte diese Pflanzenfaserin der Hefe nur durch ihre Bildung als Vegetabil, daher durchden Vegetationsprocess erzeugt worden sein (ref. 5, vol. 1,

the polymath, Baron Hermann Ludwig Ferdinandvon Helmholtz. While a medical student inBerlin, he did experiments similar to those ofMitscherlich, using an animal membrane insteadof parchment.80

Many influential scientists still adhered to vonLiebig’s view that yeast was not a living organism.However, by the time Louis Pasteur began workon alcoholic fermentation, others accepted thefindings of Cagniard-Latour, Kutzing andSchwann; these included Charles-Felix Blondeau,R. D. Thomson, Andrew Ure, ApollinaireBouchardat, J. E. Schlossberger, John Quekett andC. J. N. Balling. Blondeau12 was also a mineral-ogist; Thomson74 had studied under von Liebigat Giessen but, at that time, was a professor ofchemistry at Glasgow and appeared to have afamily bakery;73 Ure78 was a London chemist withwide interests. Bouchardat14,15 a medical man whocame from a family of wine-growers, thought beeryeast needed sugar for heat and nitrogen com-pounds for reproduction, whilst Schlossberger,who became professor of chemistry at Tubingen in1846, found66 that dry yeast contained nitrogenousmatter, cellulose, fat and minerals and consideredFigure 6. The apparatus of Mitscherlich50 using parchment

filter to divide a sugar solution into two compartments.

ACKNOWLEDGEMENTS

Warmest thanks to Savile Bradbury, PascalCandelier-Harvey, P. C. Croghan, Robert Hauer,F. W. Lichtenthaler and Ansgar Pommer forexceedingly helpful information, to Karel Sigler,

p. 179).

Yeast 14, 1439–1451 (1998)

1449 1789–1850

the Hessische Landesbibliothek, Darmstadt andKungliga Biblioteket, Stockholm for supplyingphotocopies, and to L. K. Barnett and S. A.Barnett for extensive criticisms of the script.

REFERENCES

1. Amici, G. [B.] (1820). De’ microscopj catadiottrici.Memorie di Matematica e di Fisica della SocietaItaliana delle Scienze Residente in Modena 18 (partecontenente le memorie di fisica), 107–124.

2. Anonymous. (1839). Das entrathselte Geheimnissder geistigen Gahrung. Annalen der Pharmacie 29,100–104.

3. Appert, [C.] (1812). The Art of Preserving All Kindsof Animal and Vegetable Substances for SeveralYears, 2nd edn. Black, Parry and Kingsbury,London (English translation of L’Art de ConserverPendant Plusieurs Annees Toutes les SubstancesAnimales et Vegetales, Paris, 1810).

4. Baeyer, A. [J. F. von.] (1870). Ueber dieWasserentziehung und ihre Bedeutung fur dasPflanzenleben und die Gahrung. Berichte derDeutschen Chemischen Gesellschaft zu Berlin 3,63–75.

5. Balling, C. J. N. (1845). Die GahrungschemieWissenschaftlich Begrundet und in ihrerAnwendung auf die Weinbereitung, Bierbrauerei,Branntweinbrennerei und Hefenerzeugung PractischDargestellt. Calve’schen. Prague.

6. Barnett, J. A. (1997). A historical survey of thestudy of yeasts. In Zimmerman, F. K. and Entian,K.-D. (Eds), Yeast Sugar Metabolism. Technomic,Lancaster, USA.

7. Bartholdy, P. M., Kenner, J. and McKie,D. (1944). Wohler’s work on urea. Nature 154,150–151.

8. Barton, A. A. (1950). Some aspects of cell divisionin Saccharomyces cerevisiae. Journal of GeneralMicrobiology 4, 84–86.

9. Beale, L. S. (1865). How to Work with the Micro-scope, 3rd edn. Harrison, London.

10. Berzelius, J. J. (1806). Forelasningar i Djurkemien.Delen, Stockholm.

11. Berzelius, J. [J.] (1839). Weingahrung. Jahres-Bericht uber die Fortschritte der PhysischenWissenschaften von Jacob Berzelius 18, 400–403.

12. Blondeau, C. (1847). Des fermentations. Journal dePharmacie et de Chimie 12, 244–261, 336–343.

13. Boerhaave, H. (1735). Elements of Chemistry.Pemberton, London (translated from LatinElementa Chemiae (1732), Lipsiae).

14. Bouchardat, [A.] (1844a). Memoire sur les fermentsalcooliques. Comptes Rendus Hebdomadairesdes Seances de l’Academie des Sciences, Paris 18,
1120–1125.

15. Bouchardat, [A.] (1844b). Memoire sur les fermentsalcooliques. Journal de Pharmacie des SciencesAccessoires 6, 26–31.

16. Bradbury, S. (1967). The quality of the imageproduced by the compound microscope: 1700–1840. In Bradbury, S. and Turner, G. L’E. (Eds),Historical Aspects of Microscopy. Heffer,Cambridge, pp. 151–173.

17. Bulloch, W. (1938). The History of Bacteriology.Oxford University Press, London.

18. Cagniard-Latour, [C.] (1836a). Fermentation.L’Institut No. 164, June 29, p. 209.

19. Cagniard-Latour, [C.] (1836b). Productionsorganisees. L’Institut No. 166, July 15,pp. 224–225.

20. Cagniard-Latour, [C.] (1836c). Fermentation.L’Institut No. 167, July 20, p. 237.

21. Cagniard-Latour, [C.] (1837). Memoire sur lafermentation vineuse. Comptes Rendus Hebdo-madaires des Seances de l’Academie des Sciences,Paris 4, 905–906.

22. Cagniard-Latour, [C.] (1838). Memoire sur lafermentation vineuse. Annales de Chimie et dePhysique 68, 206–222.

23. Colin, [J. J.] (1825). Memoire sur la fermentationdu sucre. Annales de Chimie et de Physique 28,128–142.

24. Desmazieres, J. B. [H. J.] (1827). Recherchesmicroscopiques et physiologiques sur le genreMycoderma (2). Annales des Sciences Naturelles 10,42–67.

25. Dumas, [J. B.] (1843). Traite de Chimie Appliqueeaux Arts, Vol. 6. Bechet jeune, Paris.

26. Evennett, P. J. (1996). Ernst Abbe and the devel-opment of the modern microscope. Proceedings ofthe Royal Microscopical Society 31, 283–292.

27. Fittig, R. (1871). U}ber die Constitution der Sogen-annten Kohlenhydrate. Fues, Tubingen (A 35-pagetreatise, held in the Hessische Landesbibliothek,Darmstadt).

28. Florkin, M. (1972). A history of biochemistry. InFlorkin, M. and Stotz, E. M. (Eds), ComprehensiveBiochemistry, Vol. 30. Elsevier, Amsterdam,pp. 23–343.

29. Fredericq, L. (1884). Theodore Schwann, sa Vie etses Travaux. Desoer, Liege.

30. Fruton, J. S. (1972). Molecules and Life. Wiley-Interscience, New York.

31. Gay-Lussac, [J. L.] (1810). Extrait d’une memoiresur la fermentation. Annales de Chimie 76, 245–259.

32. Gay-Lussac, [J. L.] (1815). Sur l’analyse del’alcohol et de l’ether sulfurique, et sur les produitsde la fermentation. Annales de Chimie 95, 311–318.

33. Gillispie, G. C. (Ed.) (1970–1990). Dictionary ofScientific Biography. Scribner, New York.

34. Harden, A. (1932). Alcoholic Fermentation, 4th
edn. Longmans, Green, London.
Yeast 14, 1439–1451 (1998)

1450 . .

35. Hofmann, A. W. (Ed.) (1888). Aus Justus Liebig’sund Friedrich Wohler’s Briefwechsel in den Jahren1829–1873, Vol. 1. Vieweg, Braunschweig.

36. Johnson, S. (1755). A Dictionary of the EnglishLanguage. Longman, London.

37. Keilin, D. (1966). The History of Cell Respirationand Cytochrome. Cambridge University Press,Cambridge.

38. Kohler, R. (1971). The background of EduardBuchner’s discovery of cell-free fermentation.Journal of the History of Biology 4, 35–61.

39. Kreger-van Rij, N. J. W. (1962). The use ofbiochemical criteria in the taxonomy of yeasts.Symposium of the Society for General Microbiology12, 196–211.

40. Kutzing, F. (1837). Microscopische Untersuchun-gen uber die Hefe und Essigmutter, nebst mehrerenandern dazu gehorigen vegetabilischen Gebilden.Journal fur Praktische Chemie 11, 385–409.

41. Lavoisier, [A. L.] (1789). Traite Eu lementaire deChimie. Cuchet, Paris (translated by R. Kerr, 1790,as Elements of Chemistry, Creech, Edinburgh).

42. Lipman, T. O. (1966). The response to Liebig’svitalism. Bulletin of the History of Medicine 40,511–524.

43. Lipman, T. O. (1967). Vitalism and reductionism inLiebig’s physiological thought. Isis 58, 167–185.

44. Lister, J. J. (1830). On some properties in achro-matic object-glasses applicable to the improvementof the microscope. Philosophical Transactions of theRoyal Society of London 120, 187–200.

45. Loffler, F. [B.] (1887). Vorlesungen uber dieGeschichtliche Entwicklung der Lehre von denBakterien. Vogel, Leipzig.

46. Loschmidt, J. (1861). Konstitutionsformeln derOrganischen Chemie in Graphischer Darstellung.Engelmann, Leipzig.

47. McKie, D. (1944). Wohler’s ‘synthetic’ urea andthe rejection of vitalism: a chemical legend. Nature153, 608–610.

48. Meyen, [F.] J. [F.] (1838). Jahresbericht uber dieResultate der Arbeiten im Felde der physiolo-gischen Botanik von dem Jahre 1837. Archiv furNaturgeschichte 4(2), 1–186.

49. Mitscherlich, [E.] (1820). Ueber die Krystallisationder Salze, in denen das Metall der Basis mitzwei Proportionen Sauerstoff verbunden ist.Abhandlungen der Mathematischen Klasse derKoniglich-Preussischen Akademie der Wissen-schaften aus dem Jahren, 1818–1819, pp. 427–437.

50. Mitscherlich, E. (1841). U}ber die chemische Zerset-zung und Verbindung vermittelst Contactsubstan-zen, als Fortsetzung seiner Abhandlung uber diechemische Verwandtschaftskraft. Bericht uber diezur Bekanntmachung Geeigneten Verhandlungen derKoniglich Preussischen Akademie der Wissenschaf-
ten zu Berlin, pp. 379–396 (also published in 1842,

Annalen der Physik und Chemie 55, 209–229 andAnnalen Chemie Pharmacie 44, 186–206).

51. Nord, F. F. and Weiss, S. (1958). Fermentationand respiration. In Cook, A. H. (Eds) TheChemistry and Biology of Yeasts. Academic Press,New York, pp. 323–368.

52. Partington, J. R. (1962). A History of Chemistry,Vol. 3. Macmillan, London.

53. Partington, J. R. (1964). A History of Chemistry,Vol. 4. Macmillan, London.

54. Payen, [A.] and Persoz, [J.] (1833). Memoire sur ladiastase, les principaux produits de ses reactions, etleurs applications aux arts industriels. Annales deChimie et de Physique 53, 73–92.

55. Persoon, C. H. (1796). Observationes Mycologicae.Wolf, Lipsiae.

56. Pigman, W. (1957). The Carbohydrates. AcademicPress, New York.

57. Pigman, W. and Horton, D. (1972). Structure andstereochemistry of the monosaccharides. InPigman, W. and Horton, D. (Eds). The Carbo-hydrates: Chemistry and Biochemistry, 2nd edn,Vol. IA. Academic Press, New York, pp. 1–67.

58. Quekett, J. [T.] (1852a). A Practical Treatise on theUse of the Microscope, 2nd edn. Bailliere, London.

59. Quekett, J. [T.] (1852b). Lectures on Histology.Bailliere, London.

60. Quevenne, T. A. (1838a). Eutude microscopique etchimique du ferment, suivie d’experiences sur lafermentation alcoolique. Journal de Pharmacie etdes Sciences Accessoires 24, 265–288.

61. Quevenne, T. A. (1838b). Memoire sur le ferment.Deuxieme partie. De la fermentation alcoolique.Journal de Pharmacie et des Sciences Accessoires24, 329–352.

62. Quevenne, T. A. (1838c). Sur le ferment diabetique.Journal de Pharmacie et des Sciences Accessoires24, 36–38.

63. Redding, C. (1833). A History and Description ofModern Wines. Whittaker, Treacher and Arnot,London.

64. Robiquet, [P.-J.] and Boutron-Charlard, [A. F.](1830). Nouvelles experiences sur les amandesameres, et sur l’huile volatile qu’elles fournissent.Annales de Chimie et de Physique 44, 352–382.

65. Saint-Hilaire, I. G. and Edwards, M. (1838).Rapport sur une note de M. Mandl, relative ala forme des globules du sang chez quelquesmammiferes. Comptes Rendus Hebdomadairesdes Seances de l’Academie des Sciences, Paris 7,1136–1143.

66. Schlossberger, J. [E.] (1844). Ueber die Natur derHefe, mit Rucksicht auf die Gahrungserschein-ungen. Annalen der Chemie und Pharmacie 51,193–212.

67. Schwann, [T.] (1837a). [No title] Isis von Oken HeftV Versammlung der Naturforscher und Aerzte zu
Jena am 18. September 1836, column 524.
Yeast 14, 1439–1451 (1998)

1451 1789–1850

68. Schwann, T. (1837b). Vorlaufige Mittheilung,bettreffend Versuche uber die Weingahrung undFaulniss. Annalen der Physik und Chemie 41,184–193.

69. Schwann, T. (1839). Mikroskopische Untersuchun-gen uber die U}bereinstimmung in der Struktur unddem Wachsthum der Thiere und Pflanzen. Verlagder Sander’schen Buchhandlung (G.E. Reimer),Berlin.

70. Schwann, T. (1847). Microscopic Investigations onthe Accordance of the Structure and Growth ofPlants and Animals (translation of ref. 69 by H.Smith). Sydenham Society, London.

71. Stahl, G. E. (1697). Zymotechnia Fundamentalis,seu fermentationis theoria generalis . . . simulqueexperimentum novum sulphur verum arte produ-cendi. Salfeldius (?Halle). (German edition, 1748,Zymotechnia Fundamentalis oder allgemeine Grund-Erkantniß der Gahrungs-Kunst, Kunkel, Stettin andLeipzig.)

72. Thenard, [L. J.] (1803). Memoire sur la fermenta-tion vineuse. Annales de Chimie 46, 294–320.

73. Thomson, R. D. (1852a). Zusammensetzung derHefe aus Hrn. Thomson’s Backerei bei Glasgow.Annalen der Chemie und Pharmacie 82, 372.

74. Thomson, R. D. (1852b). Ueber die Natur und diechemischen Wirkung der Essigmutter. Annalen derChemie und Pharmacie 83, 89–93.

75. Turner, G. L’E. (1967). The microscope as a tech-nical frontier in science. In Bradbury, S. andTurner, G. L’E (Eds), Historical Aspects ofMicroscopy. Heffer, Cambridge, pp. 175–199.

76. Turpin, [P. J. F.] (1838). Memoire sur la cause et leseffets de la fermentation alcoolique et aceteuse.Comptes Rendus Hebdomadaires des Seances del’Academie des Sciences, Paris 7, 369–402.

77. Turpin, [P. J. F.] (1840). Memoire sur la cause et leseffets de la fermentation alcoolique et aceteuse.


Memoires de l’Academie Royale des Sciences del’Institut de France 17, 93–180.

78. Ure, [A.] (1840). Versuche uber die Gahrung.Journal fur Praktische Chemie 19, 183–187.

79. van Cittert, P. H. and van Cittert-Eymers, J. G.(1951). Some remarks on the development of thecompound microscopes in the 19th Century. Pro-ceedings of the Koninklijke Nederlandsche Akademievan Wetenschappen 54, 73–80.

80. [von] Helmholtz, [H. L. F.] (1843). Ueberdas Wesen der Faulnis und Gahrung. Archivfur Anatomie, Physiologie und WissenschaftlicheMedicin 5, 453–462 (also published 1844, Journalfur Praktische Chemie 31, 429–437).

81. [von] Liebig, J. (1839). Ueber die Erscheinungender Gahrung, Faulniss und Verwesung, und ihreUrsachen. Annalen der Physik und Chemie 48,106–150 (also published in Annalen der Pharmacie30, 250–287).

82. von Liebig, J. (1842). Die Thierchemie oderdie Organische Chemie in ihrer Anwendung aufPhysiologie und Pathologie. Braunschweig (trans-lated by W. Gregory, 1842 Animal Chemistry orOrganic Chemistry in its Application to Physiologyand Pathology, Taylor and Walton, London).

83. Wohler, F. (1828a). Letter from Wohler toBerzelius, 22 February 1828. In Wallach, O. (Ed.)(1901) Briefwechsel Zwischen J. Berzelius und F.Wohler. Engelmann, Leipzig, pp. 205–208.

84. Wohler, F. (1828b). Ueber kunstliche Bildung desHarnstoffs. Annalen der Physik und Chemie 12,253–256.

85. Wohler, F. and [von] Liebig, J. (1836). Ueberdie Bildung des Bittermandelols. Annalen derPharmacie 22, 1–24.

Yeast 14, 1439–1451 (1998)

Documents

A history of research on yeasts 1: Work by chemists and biologists 1789–1850