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Copyright 0 1996 by the Genetics Society of America

Anecdotal, Historical And Critical Commentaries on Genetics
Edited by James F. Crow and William F. Dove

The “Genesis of the White-Eyed Mutant” in

Drosophila melanogaster: A Reappraisal

M. M. Green
Section of Molecular and Cellular Biology, University of California, Davis, California 95616

T HE science of genetics is, in all probability, unique

among thebiological sciences in that it is possible
to pinpoint precisely the date of its inception. The
GAN because he is the sole author of the brief paper,
only a bit more than three pages long. It should be
noted that the paperis dated July 7, 1910. In his discus-
rediscovery ofMENDEL’Slaws in 1900 independently by sion of MORGAN’Sfirst mutation experiment with D .
DE VRIES,CORRENS,and vON TSCHERMAKmarksthe melanogaster, KOHLERemphasizes the discovery of a pu-
start. During the subsequent decade, theuniversality of tativelyfirst mutation called with (“with trident”) in
MENDEL’Slaws among plants and animals was demon- which a pigmented triangular area appears on thetho-
strated, theDanish geneticistJOHANNSEN gavethe name rax just anterior to the adultfly’s scutellum. The follow-
gene to MENDEL’Sfactors, and the British geneticist ing quotation (pp. 41-42) is relevant: “Ross Harrison
BATESONcoined the term genetics. However, while the recalled visiting Morgan’s lab in the first days of Janu-
arithmetic of Mendelian genetics was quickly estab ary, 1910.‘There’stwo years work wasted,’he (Morgan)
lished, the cellular mechanism was unclear. Without exclaimed, havinghis handon rowsof bottles on
experimental evidence, SUITON and MONTGOMERY shelves. ‘I’ve been breeding these flies for all that time
each independently speculated on the correlation be- and have gotten nothing outof it.’ But, just a few days
tween meiotic chromosome disjunction and genesegre- later, Morgan observed a few flies witha darker pattern
gation. Sensu stn’cto, modern genetics began in 1910 than any he had seen before. Inbreeding quickly pro-
with the discovery ofthe white-eyed mutant in Drosophila duced a mutant strain, with, which had a distribution
melanogaster by T. H.MORGANand his demonstration of of pigment that was distinctly darker than wildtype
the correlation between the inheritance of this muta- which further selection did not alter . . . Visiting his
tion and the transmission of the Xchromosome. Experi- wife and newborn daughter in the hospital in the sec-
mental proof for the linkage between gene and chro- ond week ofJanuary, Morgan could talk ofnothing but
mosome came with the publication in 1916 (in Volume his newmutant.” Was MORGANreally talking about with
1, page 1 of GENETICS) of BRIDGES’monumental doc- or was he talking about white? Three pages later in his
toral dissertation on nondisjunction of the D . melanogas- narrative, KOHLERwrites, “When Lillian (sic) Morgan
ter X chromosome. recalled her husband’s visit to the hospital in January,
The recent publication of a detailed,instructive, and 1910, she remembered him talking about the whitemu-
valuable history of the roots and proliferation of Dro- tant. It must have been with, since white turned up in
sophila genetics by ROBERT E. KOHLER,intriguingly ti- May!” While it is not always necessary for historians of
tled Lords of the Fly, has reopened two issues ofhistorical science to understand the intricacies of the sciences
interest. When exactly was the whitemutation in D. mela- about which they write, there are instances when some
nogaster discovered, and did MORGANreally find this comprehension is useful in interpreting or explaining
mutation? relevant historical events. Had KOHLER appreciated
When considering the first question, it is important fully the vagaries of the with phenotype, he probably
to note that the first sentence in MORGAN’Sseminal would not have dismissed Mrs. MORGAN’Srecollection
publication describing the inheritance of white, pub- out of hand. Accordingly, several compelling reasons
lished July 22, 1910 in Science, reads as follows: “In a militate against the May, 1910 date and support a date
pedigree culture of Drosophila which had been run- in January, 1910.
ning for nearly a year through a considerable number In describing the with mutation, KOHLERwrote, “It
of generations, a male appeared with white eyes.” No wasjust what Morganexpected theprocess of speciation
date of discovery is given, nor is the finder specifically would look like!” By and large, almost every neophyte
named, althoughpresumably this must have been MOR- Drosophila geneticist used to make an attempt atdelin-
Genetics 1 4 2 329-331 (February, 1996)
330 M. M. Green

eating the genetics of with but gave it up as a hopeless scribed by KOHLER, conditions in the MORGANlab in
task. The reason is simple: the with phenotype is vari- 1910 were hardly optimal. Thus, for MORGANto find
able, overlaps wild type, and is precisely the kind of the mutant in May, complete and score the crosses,
mutant phenotype not readily amenable to Mendelian prepare the manuscript, and move the family and me-
analysis. In fact, in the first compilation of the mutants nagerie from NewYorkCity to Woods Hole between,
of D. mlanogaster by MORGAN,BRIDGES,and STURTEV- at the earliest, May 1 and July 7, is highlyunlikely.
ANT (1925), the linkage, map position, and phenotype An April date is possible but, for the same reasons,
of with are described as follows: “With I11 48k. M. (B improbable. However, the discovery of white in January
and M ’23). Semi-dominant dark trident pattern on satisfies all necessary conditions. Can the April and/or
thorax. Discarded.” (Note: M = MORGAN;B and M = May dates be rationalized with January? It is only possi-
BRIDGESand MORGAN.) It hardly seems possible that ble to speculate, but one possibility is that the date of
MORGAN would discard amutant with the qualities origin as Aprilor May was given for the time the genetic
KOHLERdescribes. More importantly, those who knew analysis was completed, not thespecific day the mutant
LILIAN MORGANknew that she was a superbDrosophila male was found.
geneticist in her own right, thediscoverer of the famous Did MORGANfind the first white mutant? Although
attached-X female, and certainly one who would not not stated in his 1910 paper, the discovery of the white
confuse with and white. In this connection, it is interest- mutant was attributed to MORGANand first explicitlyso
ing to relate here thefollowing anecdotal story concern- stated by MORGANon page 63 of his 1913 book, Heredity
ing the white eye mutant, extantin the MORGANfamily and Sex, asfollows: “In my culture, a male appeared
and disclosed during a visit my colleague C. M. RICK that had white eyes.” (No date of origin is given.) The
and I recently made to the home ofMrs. LILIANM. attribution was brought into question with the publica-
SCHERP, the MORGANdaughter whose birth was noted tion in 1941 of a book by F. E. LUTZentitled A Lot of
above as January, 1910. In the course of our lively con- Insects:Entomologyin a SuburbanGarden. In this book,
versation, Mrs. SCHERP was asked whether she knew any- LUTZdescribes the insects collected in the garden sur-
thing about the Drosophila whiteeye mutation. She rounding his residence and includes the following state-
related the following story, paraphrased here. At the ment, which occurs on page 238 and is quoted verba-
time of her birth, obstetricians commonly mildly anes- tim: “Meanwhile, something far more worthwhile
thetized women in labor in order to ease the pain of happened, more worthwhile even if my results are not
delivery. When Mrs. MORGANrecovered from the ether, to be explained by wild flies ‘contaminating’ my ‘pure
her first words were, “Oh, I do hope thewhite-eyed fly line’ of pedigreed Drosophila. Professor T. H. Morgan
is still alive.” This story was confirmed by her older visited the station and I told him that a white-eyed Dro-
sister, Mrs. EDITH WHITAKER, also participating in the sophila had appeared in one of the pedigreed strains,
conversation. Taking this story together with the quota- but that I was too busy with abnormal veins to attend
tion from KOHLER,apropos Mrs. MORGANand the white to it. H e took live descendants of thiswhite-eyed ‘sport’ and
mutant (see above), white, not with, was the crucial mu- bred them. Eventually, he got the white eye back” (emphasis
tation of January, 1910. mine). Thus, LUTZasserts that it was he who found
What is the source of the date “May, 1910” noted by the white mutant, and MORGANisolated white-eyed flies
KOHLER?In thefirst catalog of D. melanogastermutations from among the progeny of the wild flies given to him.
(MORGANet al. 1925), the origin of white is given only The situation is confounded further by a review of the
as 1910. In their 1916 compendium of sex-linked inheri- LUTZbook by RAMSEY SPILLMAN, which appeared in the
tance in D. melanogaster, MORGANand BRIDGESdate the Journal of Heredity (1942). In his review,SPILLMAN wrote
finding of white as May, 1910. (It should be noted here as follows, again verbatim: “It is surely of scientific his-
that this monograph includes a table of sex-linked mu- toric interest that, while studying Drosophila for varia-
tants found up to that time in the MORGANlaboratory. tions in the wingveins, Dr. Lutz found a white-eyed
Here, it is explicitly stated that the white-eyed mutant mutant, but having his hands full with the wing-vein
was found by MORGAN.)Subsequently, BRIDGESand problem, gave over five descendants of the white-eyed
MORGAN (1923), in describing the third-chromosome sport to Professor T. H. Morgan.” In a brief note in
eye-color mutation pink, wrote, “The first eye-color,and the Journal of Heredity entitled “Genesis of the White-
the characterjrst clearly recognized as a sharp mutation Eyed Mutant,” MORGAN(1942) rebuts SPILLMAN by not-
was ‘white’,found in April 1910, by Morgan” (emphasis ing first that SPILLMAN’S statement is not quite what
mine). Note the date and note, too, the statement that LUTZwrote. He notes further, “It is not obvious from
white, not with,was the first sharp mutation! There is this statement that the flies Lutz gave me were the de-
yet another good reason to believe that neither May scendants of the‘white-eyesport’ since it was dead when
nor April is correct and that theactual date is January. found, unless the bottle had contained a virgin female
The data containedin the 1910 paper involve four gen- and the whiteeyed male. Moreover, if it had mated
erations of flies. Under optimal culture conditions, the before death to a female, many white-eyed males would
generation time for D. melanogaster is two weeks. As de- have appeared in the next generation which was not
Perspectives 331

the case.” On equivalent genetic grounds, MORGAN genic and chromosomal. By 1925 the vast amount of
points to the inconsistency in SPILLMAN’S statement. Fi- information accumulated by MORGANand his students
nally, asMORGANemphasizes, the white mutation occurs in less than 15years was summarized in the monograph
frequently, and the white-eyed male he found is inde- The Genetics ofDrosophila. Documented therein arethose
pendent of LUTZ’S dead male. In this connection, it is fundamental principles of genetics derived from the
important to note that MORGANwas quite correct in study of Drosophila, principles that have withstood the
the matter of white mutations. Between March, 1915 test of time and that are included in all contemporary
and April, 1942, theindependentoccurrence of 27 textbooks of genetics.
white-eyed mutants is recorded in the second published Readers of this seriesmay note theirony that has been
catalog of D. melanogaster mutants (BRIDGESand identified by LEWIS(1995): A. H. STURTEVANT and G. W.
BREHME 1944). This number is in all likelihood an un- BEADLEfound that they could not agree whether the
derestimate because not all such mutants are reported. white gene was the specific white mutant (STURTEVANT)
Thus, conceivably LUTZdid find a white-eyed mutant or the entire set of alleles including wild-type (BEADLE).
which, however, left no progeny. Without progeny, I am indebted to my colleagues C. H. LANGLEY, J. H. GILLESPIE,
there is no genetics! Whether LUTZ’Sobservation TURELLIand J. J. SEKELSKY for critical comments on themanuscript.
alerted MORGANto be on the lookout for the white-eye They bear no responsibility for the opinions and conclusions ren-
dered therein.
mutation is a question that cannot be answered.
Finally, it should be noted thatwhite was not the first LITERATURECITED
sex-linked mutation discovered. In the currant moth BRIDGES, C. B., 1916 Nondisjunction as proof of the chromosome
Abraxus, DONCASTER and RAYNOR (1906) described a theory of heredity. Genetics 1: 1-52, 107-163.
trait called lacticolor segregating among wild females but BRIDGES,C.B., and K. S. BREHME,1944 The mutants of Dmsophila
mehnogmter. Carnegie Inst. Washington, Publ. 552, p. 253.
not among males. The sex-linked, recessive inheritance BRIDGES,C. B., and T. H. MORGAN,1923 The third-chromosome
of lacticolor was not understood until it was recognized group of mutant characters in Drosophila melanogmter. Carnegie
that, in Abraxus and other Lepidoptera, the female is Inst. Washington, Publ. 327, p. 251.
DONCASTER, L., and G. H. RAYNOR, 1906 Breeding experiments with
the heterogametic sex, not the male (BRIDGES 1916). Lepidoptera. Proc. Zool. SOC.Lond. Part 1: 125-133.
To sum up: the beginning of modern genetics can KOHLER,R. E., 1994 Lords of theFly, p. 321. University of Chicago
best be dated to January, 1910 with the discovery by Press, Chicago.
LEWIS,E. B., 1995 Remembering STURTEVANT. Genetics 141: 1227-
T. H. MORGANof a white-eyed D.melanogaster male. 1230.
For the science of genetics, the portent of the white LUTZ,F. E., 1941 A Lot of Insects: Entomology in a Suburban Garden,
mutation was enormous. Quickly, additional sex-linked p. 304. G. P. Putnam and Sons, New York.
MORGAN, T. H., 1910 Sex-limited inheritance in Drosophila. Science
mutants were discovered by MORGANand his students. 32: 120-122.
By 1913 STURTEVANT, with unsurpassed intuition, con- MORGAN, T. H., 1913 Heredity and Sex, p. 282. Columbia University
Press, New York.
structed the first linear genetic map of the X chromo- MORGAN, T. H., 1942 Genesis of the whiteeyed mutant. J. Hered.
some, followed by BRIDGES’ (1916) cytogenetic proof 31: 91-92.
of the chromosome theory, already cited. Crucial for MORGAN, T. H., C. B. BRIDGES and A. H. STURTEVAN, 1925 The
genetics of Drosophila. Bibliogr. Genet. 2: 1-262.
the demonstration of D.melanogaster as the genetic or- MULLER,H. J., 1918 Genetics variability, twin hybrids and constant
ganism par excellence was MULLER’S(1918) establish- hybrids in a case of balanced lethal factors. Genetics 3: 422-499.
ment of the principle of balanced lethals, the imple- SPILLMAN, R., 1942 Are insects people? J. Hered. 31: 23-24.
STURTEVANT, A. H., 1913 The linear arrangement of six sex-linked
mentation of which maderoutine
the recovery, factors in Drosophila as shown by their mode of association. J.
maintenance, and analysis of all classes of mutations, Exp. Zool. 1 4 43-59.