8It was surprising to learn how popular thispaper has been since it was aimed primarilyat dental researchers. The frequency withwhich it has been cited is probably due toseveral firsts which it reported. It was the firstdemonstration of caries induction by theorganism we now know as Streptococcusmutans and which is now highly suspect as acause of caries in humans; it was the firstreport of caries induction by a singleorganism in an animal harboring aconventional microflora, as distinguishedfrom the germfree animal model; and it wasthe first time antibiotic-resistant labeledorganisms had been utilized to trace thetransmission of an oral disease.

As in the case of a number of studies whichhave become Citation Classics serendipityplayed a prominent part in this research.Paul Keyes had obtained a strain of albinohamsters from the National Institutes of

Healths Animal Production Unit whichappeared to be virtually immune to carieswhen fed the high sucrose diet that resultedin high caries activity in golden hamsters. Atfirst, thinking that this was a geneticallymediated phenomenon, he soondiscovered that when albino and goldenhamsters were caged together both strainsdeveloped caries.1 This indicated that thealbinos did not harbor a cariogenicmicroflora but could acquire the infection oncontact with the golden hamsters.

At the time, I had been using germ freerats to test the potential cariogenicity ofpure cultures of microorganisms isolatedfrom caries in rats and humans. Recognizingthat the albino hamster would be simplerand more convenient as a test animal forthese studies, Keyes and I joined forces. Iisolated a series of organisms from carieslesions in golden hamsters and we began toinfect the albinos with them. Within a fewmonths we showed that only a single type ofstreptococcus was cariogenic. By making thisorganism resistant to streptomycin andusing selective media containingstreptomycin to re-isolate it, we had aconvenient way to show that it fulfilledKochs postulates as the cause of caries inthese animals.

It was not until several years later that welearned that a similar organism had beenisolated from human caries by Clarke2 in1924 and named Streptococcus mutans.Unfortunately, Clarke had no way todemonstrate that his organism actuallycaused caries. Ironicaliy, the success of ourstudy depended on the advent of antibiotics,for it turned out that the albino hamsterbreeding colony had been treated with anumber of antibiotics to eliminateintercurrent infections. This treatmentapparently also eliminated any cariogenicorganisms they may have harbored.

Dental caries was induced in caries-inactivealbino hamsters by oral inoculation of purecultures of a streptococcus isolated from acaries lesion of a caries active hamster. Astreptomycin-resistant mutant of thisorganism was used to demonstrate itspresence in caries lesions and to trace thetransmission of the labeled organismsbetween animals. [The SCI indicates thatthis paper has been cited over 265 timessince 1961.]

Robert J. FitzgeraldDental Research Unit

Veterans Administration HospitalMiami, FL 33125

August 14, 1980

CC/NUMBER 38SEPTEMBER 22,1980This Weeks Citation Classic

Fitzgerald R J & Keyes P H. Demonstration of the etiologic role of streptococci in experimentalcaries in the hamster. J. Amer. Dent. Ass. 61:9-19, 1960.[National Institute of Dental Research, National Institutes of Health, Bethesda, MD]

1. Keyes P H. Infections and transmissible nature of experimental dental caries.Arch. Oral Bio! 1:304-20, 1960.

2. Clarke J K. On the bacterial factor in the etiology of dental caries. Brit. J. Exp. Pathol. 5:141-7, 1924.

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