A MILESTONE IN GENETICS: Mendel s 1866 Paper

Transcription

1 A MILESTONE IN GENETICS: Mendel s 1866 Paper The paper that launched the science of genetics had the title Versuche über Pflanzenhybriden which translates from the German as Experiments with Plant-Hybrids. This paper detailed Gregor Mendel s studies on inheritance in peas. It was published in 1866 in the proceedings of the Natural History Society of Brünn. 1 Early in the previous year, Mendel had presented the results of his studies in lectures at two of the Society s meetings. Not many scientific papers have had the impact that Mendel s has had. Initially, the paper was ignored. However, when its significance was recognized, it became required reading for anyone interested in the study of heredity. Scrutiny by generations of readers has raised many questions about Mendel s paper. Did Mendel report his results literally? Is the fit between the data and the predictions of his hypotheses too good? Did he alter or fabricate the data to present the most compelling case for his hypotheses? In 1936 Ronald A. Fisher, a British statistician and geneticist, presented an analysis of Mendel s paper in the Annals of Science, a journal devoted to the history of science. 2 Fisher carefully attempted to reconstruct what Mendel actually did and when he did it. Mendel s research seems to have begun with the cultivation of stocks of peas in The first hybridizations between different varieties were apparently performed in 1858; other hybridizations were performed in Mendel followed the progeny of these crosses for as many as six generations. Fisher conjectures that Mendel began his dihybrid and trihybrid crosses in In that year, he also apparently began testcrosses to determine gametic ratios from heterozygous plants. Altogether, Mendel s experiments with peas spanned eight years from 1857 to The magnitude of these experiments is impressive. In some years Mendel grew more than 5000 pea plants in the monastery garden.

2 Fisher considers the question of whether or not Mendel s account of the experiments with peas can be taken literally: Mendel s paper is, as has been frequently noted, a model in respect of the order and lucidity with which the successive relevant facts are presented, and such orderly presentation would be much facilitated had the author felt himself at liberty to ignore the particular crosses and years to which the plants contributing to any special result might belong. Mendel was an experienced and successful teacher, and might well have adopted a style of presentation suitable for the lecture-room without feeling under any obligation to complicate his story by unessential details. The style of didactic presentation, with its conventional simplifications, represents, as is well known, a tradition far more ancient among scientific writers than the more literal narratives in which experiments are now habitually presented. 3 After examining the evidence in the paper, Fisher concludes that Mendel s account of his experiments should be taken literally: His experiments were carried out in just the way and much in the order that they are recounted. 4 Fisher also considers the question of whether or not Mendel s data agree too well with the predictions of his hypotheses. For example, using the data Mendel obtained in 1863, Fisher calculates a 2 statistic to test for the goodness of fit between the observations and the expectations. The result, 15.54, is less than half the expected value of the 2 distribution with 41 degrees of freedom, and Fisher says that so low a value could scarcely occur by chance once in 2000 trials. 5 Thus, he concludes, There can be no doubt that the data from the later years of the experiment have been biased strongly in the direction of agreement with expectation. 6 The bias in favor of the expected results is most apparent in the experiments Mendel performed to determine if F 2 plants with a dominant phenotype were homozygous or

3 heterozygous for the dominant allele. His procedure was to allow the plants to self-fertilize; then he examined 10 of the offspring. If any of the 10 showed the recessive phenotype, the parent was classified as a heterozygote. If none of the 10 showed this phenotype, it was classified as a homozygote. Fisher notes that with this procedure, some heterozygotes will incorrectly be classified as homozygotes simply by chance. The probability of this error is (0.75) 10 = Thus, the expected ratio of segregating to nonsegregating parents is not 2:1 but : , or 1.88:1.11. Among the 600 plants that Mendel tested, 399 were classified as heterozygotes and 201 were classified as homozygotes. These numbers are very close to the expectations based on a 2:1 ratio, but not so close to the expectations based on the ratio corrected for the probability of misclassifying heterozygotes as homozygotes. With this ratio, the expected numbers are heterozygotes and homozygotes. Fisher notes that the deviation of Mendel s data from these predicted numbers is to be expected once in twenty-nine trials. 7 For this discrepancy, Fisher suggests that Mendel was deceived by some assistant who knew too well what was expected. This possibility is supported by independent evidence that the data of most, if not all, of the experiments have been falsified so as to agree closely with Mendel s expectations. 8 In 2004 the respected geneticist Edward Novitski published an article about Fisher s criticism of Mendel s results. 9 Novitski concedes that overall, these results conform more closely with the ratios... theoretically expected than one might reasonably expect to obtain on a chance basis, and that Particularly troubling are those two groups of experiments in which Mendel s results are in close agreement with ratios that Mendel may have considered appropriate, but which were, according to Fisher (1936), incorrect. 10 However, Novitski argues that Fisher s criticism of Mendel especially his suggestion that some of the experimental data

4 might have been falsified is unfounded. For one thing, Mendel s procedure of ascertaining whether an F 2 plant with a dominant phenotype was homozygous or heterozygous for the dominant allele may have been affected by an error in the opposite direction of the one that Fisher described. Mendel based his decision about the genotype of a plant on the phenotypes of 10 of its progeny. Novitski proposes that for some of the plants, Mendel could not obtain the required 10 progeny. The failure rate for seed germination may have been as high as 2 percent. If fewer than 10 progeny were examined, and at least one of them had the recessive phenotype, then the parent plant could have been correctly classified as a heterozygote. However, if fewer than 10 progeny were examined say only 8 or 9 and none of them showed the recessive phenotype, what was Mendel to do? Novitski conjectures that Mendel would not have classified the parent plant as a homozygote for the dominant allele; rather, he would have excluded that plant from consideration and replaced it with another plant that had been held in reserve. The excluded plant was most likely a dominant homozygote, and the reserve plant was most likely a heterozygote. Thus, in an effort to adhere to his rule of classifying a plant as a dominant homozygote only after counting 10 dominant progeny, Mendel may have skewed his results in favor of heterozygous plants. This error would counterbalance the one that Fisher described and move the observed ratio of heterozygotes to dominant homozygotes toward 2:1, which is what Mendel reported. Novitski also suggests that Mendel may have repeated some of the experimental runs in which the results he obtained did not appear to bear out his expectations, not with any intent to deceive, but to make certain for his own benefit that those runs were in fact not bona fide cases of exceptions to his rules. Having obtained additional data, he could have either replaced the earlier deviating data with the better numbers or combined the two sets of data, which would

5 usually obscure the extent of the deviations in the first set.... It might be observed that such procedures probably exist in preparing data for publication even today. 11 As for the possibility that Mendel altered or manipulated his data, Novitski says that if he did, his alterations would stem not from any desire to mislead, but as a concession to his illprepared audience. We can imagine that at the time of writing for oral presentation, Mendel changed, for didactic purposes, some specific results that might have distracted his audience from the main theme of the article because of their seemingly aberrant nature. Surely words like fraud or dishonesty should be used with caution. Perhaps his situation can be compared to that of the competent high school science teacher who, in explaining the structure of the atom to his students, falls back on the simple Bohr model, well aware that while it is not the correct picture, it is appropriate for the audience for which it is intended. 12 QUESTIONS FOR DISCUSSION 1. Today many scientific papers contain four main sections of text Introduction, Materials and Methods, Results, and Discussion and they are usually preceded by an abstract (or summary) and followed by a bibliography of references cited. How does this format vary among journals that publish papers on genetics (e.g., Cell, Genetics, Proceedings of the National Academy of Sciences, Nature, and Science)? How does it differ from the format of papers in other disciplines such as sociology, law, history, and literature? 2. Gregor Mendel seems to have done his research to satisfy his own curiosity. He did not benefit from the research financially or professionally, and, except for space in the monastery garden and perhaps the help of a few assistants, his work did not require any other type of

6 support, say, for example, a government grant. What do these circumstances say about the kind of person Mendel was? How does he compare with professional scientists working on research projects today? 1 Mendel, G Versuche über Pflanzenhybriden. Verhandlungen Naturforshender Vereines in Brünn Fisher, R. A Has Mendel s work been rediscovered? Annals of Science 1: Ibid. 4 Ibid. 5 Ibid. 6 Ibid. 7 Ibid. 8 Ibid. 9 Novitski, E On Fisher s criticism of Mendel s results with the garden pea. Genetics 166: Ibid. 11 Ibid. 12 Ibid.