During the first decade of the twentieth century it was established that the sex of almost all many-celled biological organisms is determined at the moment of fertilization by the combination of two kinds of microscopic entities. the X and Y chromosomes,‘ This discovery was the culmination of more than two thousand years of speculation and experiment on how an animal. plant. or human becomes male or female; at the same time it provided an important con?rmation for the recently revived Mendelian genetics that was to become a central part o? modern
biology.
According to most biologists and historians who have written on the subject, the crucial step in the discovery of chromosomal sex determination was taken in I905 by Nettie M. Stevens (l36l—l9l2) and Edmund B. Wilson (l856—l939i But the scienti?c and chronological relation between their contributions has rarely been speci?ed, and the role of Stevens. who died in l9l2 before she could attain a reputation comparable to that of Wilson. has sometimes been forgotten In fact neither Stevens nor Wilson is now given adequate recognition by writers of texts and popular works on biology; most of the credit for the establishment of modern genetics usually goes to Thomas Hunt Morgan (1866—1945), who would not accept the chromosome theory until several years after the work o? Stevens and Wilson had been published.
In this article I do not attempt a de?nitive assessment of Stevens‘ contribution to the chromosome theory of sex determination; that would require much more knowledge of the technical details of her work and that of others than l possess. My purpose is primarily to cal] attention to some documents (held at the Carnegie Institution of Washington) that illuminate her relations with Wilson and Morgan. and perhaps to persuade historians of biology to investigate her work more thoroughly.
Nettie Maria Stevens was born July 7. 1861. in Cavendish. Vermont. Her father was a carpenter; she was the second of three children. the elder o? two daughters. She attended West?eld State Normal School in Massachusetts to prepare for a teaching career. Her interest in science may have been aroused during summer courses at Martha‘s Vineyard in I890 and l89l. She saved enough money from her teaching jobs to go to Stanford University, where she enrolled in [896 and received a B.A. degree in [899.3 The following year she obtained her M.A. from Stanford and entered Bryn Mawr College as a doctoral student.
One might think that going to a small women’s college would be fatal to the career of an aspiring scientist at that time. but in this case the opposite was true. Two o?the leading American biologists. E. B. Wilson and T. H. Morgan. taught successively in the biology department at Bryn Mawr. Both were on the editorial board o? the Journal of Experimental Zoology and otherwise in?uential in the scienti?c establish- ment. Though Wilson had gone to Columbia in |89l. he retained close ties with Morgan. who stayed at Bryn Mawr until I904. As a student and later a colleague o? Morgan’s, Stevens was able to keep iii touch with current research in the fast-moving ?elds of genetics. cytology, and embryology. As a promising woman scientist who had already published nine papers by the time she completed her Ph.D. in 1934 she
was eligible for special fellowships and prizes.
The Bryn Mawr President‘s European Fellowship enabled her to study at the Naples Zoological Station and at the University of Wt’irzburg. where she worked with the German biologist Theodor Boveri. Then she received an award o? $l,000 from the “Association for Maintaining the American Woman‘s Table at the Zoological Station at Naples and for Promoting Scienti?c Research among Women.” o?ered for the best paper written by a woman on a scienti?c subject} A postdoctoral research assistantship from the Carnegie Institution of Washington allowed her to continue research at Bryn Mawr, unburdened by teaching duties during the crucial years 1904-1905, when her research on the sex chromosomes was being done.
During the previous decade Boveri, W. S. Sutton, Wilson, and others had found strong evidence for the individuality of chromosomes as identifiable parts of cells (reidentifiable after division) and suggested that each chromosome may be responsible for a definite part of the hereditary endowment of an organism. Chromosomes could be duplicated during the process of reproduction but otherwise remained unaffected by their environment; thus they seemed to behave like August Weismann’s “germ plasm,” which was supposed to be isolated from the rest of the organism and excluded the possibility that acquired characteristics could be inherited. In the first edition (1896) of his influential book The Cell in Development and Inheritance, Wilson collected evidence that the seat of heredity is in the chromosomes in the cell nucleus. This treatise helped prepare American biologists to receive Mendel’s theory when it was independently rediscovered and advocated four years later by Hugo de Vries, Carl Correns, and Erich Tschermak von Seysenegg 6 and organized support for the Sutton-Boveri chromosome hypothesis.
But Wilson, Morgan, and most other biologists were not yet ready to accept the idea that sex is completely determined by chromosomes at the moment of fertilization. Instead, many believed that environmental factors such as nutrition play a major role in determining the sex of the developing embryo. 7 Wilson wrote, in the 1900 edition of The Cell , that “sex as such is not inherited. What is inherited is the capacity to develop into either male or female, the actual result being determined by the combined effect of conditions external to the primordial germ-cell.” 8 In 1903 Morgan concluded an extensive review of the subject with the paragraph:
Our general conclusion is that while recent theories have done good service in directing attention to the early determination of sex in the egg, those of them which have attempted to connect this conclusion with the assumption of the separation of male from female primordia in the germ-cells have failed to establish their point of view. The egg, as far as sex is concerned, appears to be in a sort of balanced state, and the conditions to which it is exposed, even when it is not fully formed, may determine which sex it will produce. It may be a futile attempt to try to discover any one influence that has a deciding influence for all kinds of eggs. Here, as elsewhere in organic nature, different stimuli may determine in different species which of the possibilities that exist shall become realized.
In 1902 C. E. McClung suggested that the “accessory chromosome,” discovered earlier by Hermann Henking, plays an important part in sex determination. His hypothesis was that this chromosome is “the bearer of those qualities which pertain to the male organism.” 10 This hypothesis turned out to be wrong, but it attracted the attention of other workers such as William Bateson and Miss E. R. Saunders at Cambridge University and W. E. Castle at Harvard. 11 There is some disagreement among later writers as to how much credit McClung should receive in the discovery of chromosomal sex determination, but there is no doubt that his hypothesis was extremely important in stimulating work by others.
Stevens was quick to see the possibilities opened up by McClung’s hypothesis in conjunction with the Mendelian theory of heredity. Morgan’s letter to the Carnegie Institution, November 19, 1903, in support of her application for a grant, makes it clear that she was the one who wanted to investigate sex determination by chromosomes, whereas he, the senior (though younger) partner of the team, was still under the influence of environmental theories (see Appendix). Yet this difference of opinion did not prevent them from collaborating. In fact, given a situation of mutual respect, the disagreement was fortunate for Stevens in the long run, since it meant that she published her results under her own name alone. If Morgan’s name had been on her 1905 publication, the scientific world would undoubtedly have given most of the credit to him. (See Sec. V, below.)
Both Morgan and Wilson were enthusiastic in recommending Stevens to the Carnegie Institution. Morgan wrote that “of the graduate students that I have had during the last twelve years I have had no one that was as capable and independent in research work as Miss Stevens . . .” (see Appendix). Wilson stated: “I know Miss Stevens’ work well, and it is of a very independent and admirable character from
every point of view. I consider her not only the best of the women investigators, but one whose work will hold its own with that of any of the men of the same degree of advancement.”
Stevens’ initial letter of application to the Carnegie Institution, dated July 19, 1903, indicated her situation quite clearly: she needed money to live on, and “College positions for women in Biology this year seem, however, to be very few.” She wanted to pursue the “histological side of the problems in heredity connected with Mendel’s Law” (the complete letter is given in the Appendix).
The grant was awarded, and Stevens proceeded with her research, which involved detailed examination of the chromosomes of several insects and comparison with the sex of the progeny. In a paper on the germ cells of aphids completed at the end of 1904, she failed to find McClung’s extra chromosome, but the direction of her research was clear: a review of the current state of research had convinced her that “the evidence is overwhelmingly on the side of the view that sex is determined in the egg; but to the question how sex is determined in the egg, no thoroughly convincing answer has yet been given.
Stevens was more fortunate with Tenebrio molitor, the common mealworm; males are produced by spermatozoa containing one chromosome that is clearly much smaller than the corresponding chromosome in the spermatozoa that produce fe-males. On May 23, 1905, she submitted to the Carnegie Institution a manuscript on “Studies in Spermatogenesis” for publication in the Carnegie monograph series. It was sent on May 29 to Wilson, as a member of the institution’s advisory committee, for his opinion. He returned it on June 13 with the brief statement: “It is in every way a most admirable piece of work which is worthy of publication by any learned society, and I do not hesitate to recommend it to you for publication by the Institution.”
Stevens’ monograph on spermatogenesis was published in September 1905. After describing her experiments with Tenebrio , she concluded: Since the somatic cells of the female contain 20 large chromosomes, while those of the male contain 19 large ones and 1 small one, this seems to be a clear case of sexdetermination, not by an accessory chromosome, but by a definite difference in the character of the elements of one pair of chromosomes of the spermatocytes of the first order, the spermatozoa which contain the small chromosome determining the male sex, while those that contain 10 chromosomes of equal size determine the female sex. This result suggests that there may be in many cases some intrinsic difference affecting sex, in the character of the chromatin of one-half of the spermatozoa, though it may not usually be indicated by such an external difference in form or size of the chromosomes as in Tenebrio.
It is generally stated that E. B. Wilson obtained the same results as Stevens, at the same time. Roughly speaking, this is true, but the statement must be qualified in three ways. First, Wilson happened to choose a species in which the male has one less chromosome than the female, whereas Stevens investigated the much more common case in which the male has a small chromosome (Y) corresponding to the large chromosome (X) in the female. It could later be argued that the cases are “the same in principle,” 16 but in the context of early-twentieth-century biology the Wilson case (X,0) looks like a simple reversal of McClung’s hypothesis and does not bring out clearly the dominant-recessive feature that distinguishes the modern (X,Y) theory.
Second, Wilson probably did not arrive at his conclusion on sex determination until after he had seen Stevens’ results. This is perhaps the most important point established by the documents at the Carnegie Institution. Morgan, in his obituary of Wilson, implied that Wilson discovered the crucial difference between the chromo- some numbers in Anasa tristis (22 in the female, 21 in the male) before Stevens submitted her paper: The question is sometimes asked as to the priority of Stevens’ and Wilson’s papers. Stevens’ paper was handed in on May 15, 1905 1 7 and printed in September of that year. In Wilson’s paper “Studies on Chromosomes” I (dated May 5, 1905; published August 1905) he says in a footnote: “The discovery, referred to in a preceding footnote, that the spermatogonial number of Anasa is 21 instead of 22, again goes far to set aside the difficulties [of McClung’s hypothesis] here urged. Since this paper was sent to press I have also learned that Dr. N. M. Stevens (by whose kind permission I am able to refer to her results) has independently discovered in a beetle, Tenebrio, a pair of unequal chromosomes that are somewhat similar to the idiochromosomes in Hemiptera and undergo a corresponding distribution to the spermatozoa. She was able to determine, further, the significant fact that the small chromosome is present in the somatic cells of the male only, while in those of the female it is represented by a larger chromosome. These very interesting discoveries, now in course of publication, afford, I think, a strong support to the suggestion made above; and when considered in connection with the comparison I have drawn between the idiochromosomes and the accessory show that McClung’s hypothesis may, in the end, prove to be well founded.”
But Morgan overlooked the fact that the “preceding footnote” in Wilson’s paper, mentioned in the above quotation, was not in the original paper as submitted on May 5; it begins “Since this paper was sent to press I have determined beyond the possibility of doubt, I think, that the number of spermatogonial chromosomes in Anasa tristis is 21, not 22. . . .” 19 Wilson emphasizes in this footnote the special care he took to verify this result, which disagreed with the results of other biologists; it is hardly likely (and he does not claim) that he established the result in the period of less than four weeks between May 5 and the time he received Stevens’ paper from the Carnegie Institution for review.
It is true that Wilson’s paper “Studies on Chromosomes” (part I) was published before Stevens’ — in fact it appeared in the same issue of the Journal of Experimental Zoology (August 1905) as Stevens’ paper on aphids that had been submitted to this quarterly journal in December 1904. 20 But in view of Wilson’s position on the editorial board, the fact that his paper was published with a relatively short time lag (three months, compared to eight months for Stevens’) perhaps should not be used to establish his priority.
Nevertheless, one may still reject the above two arguments — one may claim that Wilson did arrive at essentially the same conclusion as Stevens, before he received her paper at the end of May 1905. Then look at his short article, dated October 3, 1905, published in Science on October 20 of that year. This is the article usually cited as the first report of Wilson’s discovery of sex determination. 21 Although he begins by stating that there is “no doubt that a definite connection of some kind between the chromosomes and the determination of sex exists in these animals,” he concludes by reverting to a semi-environmental theory:
. . . great, if not insuperable, difficulties are encountered by any form of the assumption that these chromosomes are specifically male or female sex determinants. It is more probable . . . that the difference between eggs and spermatozoa is primarily due to differences of degree or intensity, rather than of kind, in the activity of the chromosome groups in the two sexes; and we may here find a clue to a general theory of sex determination that will accord with the fact observed in hemiptera . . . during the synaptic and growth periods . . . these chromosomes play a more active part in the metabolism of the cell in the female than in the male. The primary factor in the differentiation of the germ cells may, therefore, be a matter of metabolism, perhaps one of growth.
Wilson in 1905 was reluctant to come down as firmly as Stevens on the side of instantaneous sex determination by the mere presence or absence of a particular type of chromosome. Perhaps his greater knowledge of the complexities of the data available at that time made him properly cautious about jumping to such a simplistic conclusion; perhaps Stevens was only making a rash generalization unjustified by the evidence. Her understanding of the dominant-recessive properties of X and Y chromosomes, based on Castle’s modification of Mendelian inheritance, 23 was not the same as the modern view (in which Y is always dominant and X always recessive), so one cannot accuse Wilson of rejecting a completely correct theory.
Nevertheless, there is no doubt that as late as 1906 Stevens was still ahead of Wilson in realizing the significance of their discovery. She wrote: Wilson 24 suggests as alternatives to the chromosome sex determinant theory according to Mendel’s Law, (1) that the heterochromosomes may merely transmit sex characters, sex being determined by protoplasmic conditions external to the chromosomes; (2) That the heterochromosomes may be sex-determining factors only by virtue of difference in activity or amount of chromatin, the female sex chromosome in the male being less active. 25
She could cite evidence against both of these alternatives, and concluded: “On the whole, the first theory, which brings the sex determination question under Mendel’s Law in a modified form, seems most in accordance with the facts, and makes one hopeful that in the near future it may be possible to formulate a general theory of sex determination.”
Nettie Stevens benefited from the encouragement and support of the scientific establishment during the time she was doing her most important work, but it does not appear that she later gained a reputation or material rewards commensurate with her accomplishments. Failure to win a Nobel Prize (if one thinks the discovery deserved it) can be explained by the fact that the significance of sex chromosomes in genetics was not generally appreciated before her death; Morgan had to wait until 1933 for his trip to Stockholm, and Wilson never did make it. 27 More serious is the fact that most modern textbooks, if they mention Stevens at all, give the impression that she worked with or following Wilson. 28 Because of Wilson’s more substantial contributions in other areas, he tends to be given most of the credit for this discovery, as a result of the operation of the “Matthew effect” noted by sociologist Robert Merton. 29 (“Unto every one that hath shall be given, and he shall have abundance; but from him that hath not shall be taken away even that which he hath” — Matthew XXV: 29). The most extreme example of this effect is the occasional ascription of the discovery of chromosomal sex determination to T. H. Morgan, simply because he is considered the most important American geneticist in the first half of the twentieth century and hence the only one mentioned in superficial accounts.
Those who seek outstanding female scientists to inspire the next generation of talented women to follow scientific careers seem to have overlooked Nettie Stevens. This may be partly because most books that do mention her work identify her only as “N. M. Stevens,” giving no hint of gender. 31
Even Bryn Mawr College was somewhat tardy in recognizing the achievements of its most eminent woman biologist, as the Stanford Alumnus pointed out in its obituary (February 1913). Her highest position there was Associate in Experimental Morphology. The Trustees of Bryn Mawr finally created for her a research professorship, but she was never able to occupy it; shortly afterwards she died of carcinoma of the breast, on May 4, 1912, at Johns Hopkins Hospital in Baltimore.
