Did van Leeuwen­hoek Ob­serve Yeast Cells in 1680?

by Nanne Nan­ninga

It is com­mon knowl­edge that beer was pro­duced by the an­cient Egyp­tians and that van Leeuwen­hoek (1632–1723) was the first to see yeast cells. How­ever, what was de­fined as yeast in the sev­en­teenth cen­tury is dif­fer­ent from that of to­day. So did van Leeuwen­hoek re­ally ob­serve yeast? In at­tempt­ing to an­swer this ques­tion it might be help­ful to de­scribe some fun­da­men­tal work on yeast by Charles Cagnard-La­tour (1777–1859) pub­lished in 1838. (Re­call that the cell the­ory dates from 1839). This tells us of the beer brew­ing and wine mak­ing state of the art around that time. It was known that the ad­di­tion of yeast to prop­erly treated grains of ce­re­als would pro­duce al­co­hol and car­bon diox­ide from the ex­tracted malt sug­ars. In the times of van Leeuwen­hoek yeast was con­sid­ered an inan­i­mate paste with no con­nec­tion to liv­ing cells. What did Cagnard-La­tour see? It is im­por­tant to use the term "see" be­cause, as he em­pha­sized, he wished to ap­proach yeast re­search in a new way, that is, by em­ploy­ing a mi­cro­scope. (This ap­proach was also fol­lowed by F. T. Kützig and Th. A. Schwann at the same time.)

Cagnard-La­tour went to an Eng­lish style brew­ery in Paris where every hour he took a sam­ple for study from the con­tainer in which the beer was be­ing pro­duced. Ini­tially he ob­served glob­ules of dif­fer­ent sizes, later he saw small vesi­cles pro­trud­ing from the glob­ules that had arisen through bud­ding (Fr. par bour­geons), and fi­nally, af­ter four hours, only dou­blets were present. He con­cluded the ini­tial small vesi­cles had in­creased in size through growth. If so, the dou­blets should not be ad­ven­tious ag­gre­gates. To test this he forcibly shook his mi­cro­scopic prepa­ra­tion with a kind of thorn (Fr. poinçon) and ob­served that the dou­blets re­mained in­tact. Re­mark­ably, he no­ticed that upon dis­so­lu­tion of the dou­blets a scar re­mained at a vari­able place on the globule's sur­face. He used the terms ci­ca­trice (Fr. for scar) and mar­que om­bil­i­cale (Fr. for navel).

The num­ber of glob­ules in­creased in time, as did their to­tal weight. His gen­eral con­clu­sion was that beer brew­ing or fer­men­ta­tion in­volves the growth and pro­lif­er­a­tion of an or­gan­ism. He also ob­served that com­mer­cial yeast con­tains sin­glets ex­clu­sively. So at this stage yeast was re­de­fined, chang­ing from an inan­i­mate to an an­i­mate ob­ject. But was it an an­i­mal or a plant? Here he used the same ap­proach as van Leeuwen­hoek. The "lit­tle an­i­mals" of the lat­ter were con­sid­ered an­i­mals be­cause they ex­hib­ited au­tonomous move­ment. Be­cause yeast did not, Cagnard-La­tour clas­si­fied his grow­ing glob­ules as plants. Cagnard-La­tour made an­other ob­ser­va­tion that I find highly rel­e­vant to the in­ter­pre­ta­tion of van Leeuwenhoek's data. He saw his glob­ules emit gas bub­bles which caused in­di­vid­ual glob­ules to rise to the sur­face of the fer­ment­ing fluid in the fer­men­ta­tion vat.

Now, what about the ob­ser­va­tions of van Leeuwen­hoek?

Ac­cord­ing to Cagnard-La­tour in a foot­note to his pa­per of 1838, van Leeuwen­hoek con­sid­ered yeast to be de­rived from flour. When pre­sent­ing his work in Paris to the Acad­emy of Sci­ences in 1837, he men­tions that he had not been aware ear­lier of van Leeuwenhoek's work. How­ever, the first sen­tence in van Leeuwenhoek's let­ter of June 14, 1680, di­rected to Mr. Thomas Gale (1635/1636–1702), a fel­low of the Royal So­ci­ety, sum­ma­rized his re­sults in quite a straight­for­ward man­ner: I have made sev­eral ob­ser­va­tions con­cern­ing yeast and seen through­out that the afore­said con­sisted of glob­ules float­ing through a clear sub­stance, which I judged to be beer...Van Leeuwen­hoek con­tin­ues the above sen­tence by stat­ing: ...in ad­di­tion I saw clearly that every glob­ule of yeast ("gist" in Dutch) in turn ex­isted of six dis­tinct glob­ules and that just of the same size and fab­ric as the glob­ules of our blood. Note that the di­am­e­ter of a red blood cell is roughly 7 µm, which is com­pa­ra­ble to the size of a yeast cell.
 

Draw­ing by van Leeuwen­hoek of his wax model, taken from his let­ter of 14 June 1680 to Thomas Gale. This might be the first time in the his­tory of bi­ol­ogy that an ex­per­i­men­tal­ist uses a model to ex­plain his obser­vations to the reader! Source

Con­tin­u­ing his let­ter, van Leeuwen­hoek re­ports that when sam­pling beer be­ing brewed he ob­serves in the fluid "many small par­ti­cles" (seer veel kleyne deelt­jens) which cause the beer to ap­pear tur­bid. Some par­ti­cles were round, oth­ers ir­reg­u­larly shaped and some were big­ger than oth­ers and they seemed ag­gre­gates of 2, 3 or 4 of the said par­ti­cles and oth­ers again of 6 glob­ules and the lat­ter con­sti­tuted a per­fect glob­ule of yeast. He in­ter­preted this as ag­gre­ga­tion (strem­ming in Dutch) and made many vain ef­forts to record the ag­gre­ga­tion process. (Re­call that Cagnard-La­tour did the op­po­site: he at­tempted to demon­strate that yeast dou­blets arise from sin­glets.) To fur­ther ap­pre­ci­ate the spa­tial or­ga­ni­za­tion of the yeast glob­ule (the sex­tet), van Leeuwen­hoek made a model com­posed of 6 wax glob­ules which he arranged in such a way that all 6 glob­ules could be seen when viewed from above. Clearly, this is an early, if not the ear­li­est, ex­am­ple of model build­ing for the in­ter­pre­ta­tion of sci­en­tific data.
 

An early let­ter writ­ten in van Leeuwenhoek's own hand, 16 April 1674 to Henry Old­en­burgh. Source

Van Leeuwen­hoek spec­u­lated about the ori­gin of the glob­ules. (Note that he de­noted sin­gle par­ti­cles as well as sex­tets as glob­ules.) Flour or meal of ce­re­als is com­posed of glob­ules which are first de­hy­drated by heat and when united with wa­ter which we are al­lowed to call beer, very small par­ti­cles in the beer ag­gre­gate upon cool­ing to form a big­ger par­ti­cle, the sin­glet glob­ule. The sin­glets ag­gre­gate to form a sex­tet, the yeast glob­ule. (I did not trans­late this lit­er­ally to keep it read­able.) In other words, ac­cord­ing to van Leeuwen­hoek, yeast arises out of ce­real flour or meals dur­ing brew­ing and as such yeast is not a dis­tinct bi­o­log­i­cal en­tity.

We are now ap­proach­ing the an­swer to our main ques­tion. As Cagnard-La­tour did later, Van Leeuwen­hoek also ob­served air bub­bles com­ing to the sur­face of the beer in the brew­ing con­tainer. He calls them "air" be­cause, un­like Cagnard-La­tour, he was un­fa­mil­iar with gaseous car­bon diox­ide. To his re­gret, he was un­able to trace the ori­gin of the "air." Then fol­lows a very strik­ing in­ter­mezzo which starts with: But what shall we say of the nu­mer­ous air bub­bles that were pro­duced from lob­ster eye, when we lay them in vine­gar? In sum­mary, he noted that if enough air bub­bles re­main at­tached to pieces of lob­ster eye, the lat­ter float to the sur­face of the vine­gar. When the bub­bles dis­solve in the air, the pieces of lob­ster eye sink again. This process re­peats as long as air bub­bles are pro­duced. Sur­pris­ingly, van Leeuwen­hoek makes no ex­plicit con­nec­tion to yeast. The term lob­ster eye (kreeften-oog in Dutch) in the let­ter of van Leeuwen­hoek is not clear-cut. It seems also to re­fer to a ma­te­r­ial sub­stance (a stoffe in Dutch), which af­fects the salin­ity of an acidic so­lu­tion.

This lob­ster story re­minds one of the ob­ser­va­tions later made by Cagnard-La­tour on yeast, as de­scribed above. But why did van Leeuwen­hoek de­scribe his ear­lier mi­cro­scopic ob­ser­va­tions on frag­ments of lob­ster eye in his let­ter de­scrib­ing his ob­ser­va­tions of yeast glob­ules? Pre­sum­ably be­cause, I be­lieve, he was in­spired by the be­hav­iour of yeast in a brew­ing con­tainer. Thus, ir­re­spec­tive of the iden­tity of lob­ster eye, a rea­son­able an­swer to our main ques­tion is that van Leeuwen­hoek did in­deed ob­serve grow­ing yeast cells, de­spite the fact that he could not place them within a bi­o­log­i­cal frame­work.

Author's Note: Trans­la­tions of van Leeuwenhoek's Dutch to Eng­lish are mine, and thus I am re­spon­si­ble for any er­rors.

Pri­mary sources for this con­tri­bu­tion in­clude the 1680 let­ter of van Leeuwen­hoek that has been kindly brought to my at­ten­tion by Warnar Moll. The ref­er­ence to the 1838 pa­per of Cagnard-La­tour I found in the el­e­gant 1871 pa­per of Thomas Hux­ley on yeast. Also highly rec­om­mended is a schol­arly re­view on 19th cen­tury "bio­chem­istry" by Her­bert C. Fried­mann. Very in­for­ma­tive is the re­view of James A. Bar­nett.

An­toni van Leeuwen­hoek. Let­ter to Thomas Gale of June 14^th 1680, pp. 6–10 in the sec­ond print­ing car­ried out by Hen­drik van Croon­evelt at Delft in 1694.

M. Cagnard-La­tour. Mé­moire sur la fer­men­ta­tion vineuse: présenté á L'Académie des Sci­ences, le juin 1837. Comptes ren­dus des séances de l' Académie des Sci­ences, l'octobre 1838.

Thomas Henry Hux­ley. Yeast. The Con­tem­po­rary Re­view (1871). Col­lected Es­says VIII.

Her­bert C. Fried­mann. From Friedrich Wöhler's urine to Ed­uard Buchner's al­co­hol. From Beer in an Old Bot­tle: Ed­uard Buch­ner and the Growth of Bio­chem­i­cal Knowl­edge, pp. 67–122, ed. A. Cor­nish-Bow­den, Uni­ver­si­tat de Va­len­cia, Va­len­cia Spain 1997.

J. A. Bar­nett. Be­gin­nings of mi­cro­bi­ol­ogy and bio­chem­istry: the con­tri­bu­tion of yeast re­search. Mi­cro­bi­ol­ogy 149: 557–567 (2003).

Warnar Moll. An­tonie van Leeuwen­hoek.

Nanne Nan­ninga is Emer­i­tus Pro­fes­sor of Mol­e­c­u­lar Cy­tol­ogy, Swammer­dam In­sti­tute for Life Scien­ces, Uni­ver­sity of Am­s­ter­dam, The Nether­lands.