Review Endeavour Vol.27 No.2 June 2003 63 Mendel and modern genetics: the legacy for today Garland E. Allen Department of Biology, Washington University, St Louis, MO 63130, USA The legacy of Mendel’s pioneering studies of hybridiz- offered for his breeding data seemed reminiscent of so ation in the pea continues to influence the way we many of the speculative, particulate theories of heredity understand modern genetics. But what sort of picture that had abounded in the post-Darwinian era, including did Mendel himself have of his work and its ultimate Darwin’s own ‘provisional hypothesis of pangenesis’, uses, and how does that picture compare with the col- August Weismannn’s elaborate theory of ‘ids, idants and lection of ideas and methodologies that was put for- biophors’, Ernst Haeckel’s imaginary ‘plastidules’, and ward in his name and later became known as Hugo de Vries’ postulated ‘pangenes’. Consequently, to ‘Mendelism’? With genetics standing at the center of some, at least, Mendel’s work seemed like just one more of our present biomedical and biotechnological research, the sort of abstract proposals they had encountered all too an examination of the history of our concepts in the frequently. In point of fact the paper probably seemed field can help us better understand what we should and extraordinarily dense, with no illustrations but numerous should not expect from current genetic claims. For that binomial expansions, which were likely to have been a put- enterprise there is no better starting place than Mendel off for many biologists who at the time were notoriously himself. math-shy. For whatever reason, for the first decade of its re-emergence into the scientific world, Mendel’s contri- As we celebrate 50 years of the Watson–Crick model of bution remained controversial at best, dismissed by DNA, it is worth stepping back to take a longer look at the significant sections of the biological community at worst. work that started it all: the pioneering hybridization What ultimately served to establish Mendelism on more studies of the pea (Pisum sativum) and bean (Phaesolus) firm ground between 1900 and 1915 was: (1) its extension by Gregor Johann Mendel (1822–1884) (Fig. 1). Although to an increasingly wide variety of organisms; and (2) its Mendel’s work was first presented at a meeting of the unification with the cytological work on chromosomes Bru¨ nn Natural History Society in 1865, and published in carried out principally through the work of Thomas Hunt its Proceedings in 1866, it received only a modicum of Morgan (1866–1945) and his young, enthusiastic team of attention until 1900, when it was more or less simul- investigators at Columbia University between 1911 and taneously rediscovered by three different investigators: 1925. The work of the Morgan school demonstrated that Carl Correns (1864–1933) in Germany, Hugo De Vries the abstract elements or ‘factors’ discussed by early 20th- (1848–1935) in the Netherlands, and Erich von Tscher- century Mendelians could be regarded as discrete, mak-Szeneygg (1871–1962) in Austria. Whilst all three material units arranged linearly along the chromosomes, found Mendel’s work suggestive, it is not clear that any of them really saw the significance of what he had done, and none of the ‘rediscoverers’ became a major promoter of the new genetics [1]. The first major publicist for Mendel’s work was William Bateson (1865–1926) in England. Through the Royal Horticultural Society, Bateson had Mendel’s paper trans- lated into English for the first time, and wrote a general exposition that laid out the basic principles of what soon came to be known as ‘Mendelism’ [2]. Bateson’s work brought Mendel to the attention of numerous workers in England, Scandinavia and the United States, in particular to many of those involved in practical animal and plant breeding [3]. Although there was reluctance in some quarters to embrace Mendel’s work immediately – Fig. 1. Gregor Johann Mendel (standing, second from right) with members of the especially among academic biologists – by the end of the Augustinian monastery of StThomas in Brno in about 1862. Mendel can be seen first decade of the 20th century, the theory had gained a observing a plant specimen. Others in the photograph of particular importance in Mendel’s life are the Abbot Cyrill Napp (seated, second from right) and Matous considerable following. However, the explanation Mendel Kla´ cel (seated, first from right), who was also interested in natural science and philosophy, and with whom Mendel had frequent lively discussions. Reproduced, Corresponding author: Garland E. Allen ([email protected]). with permission, from [5], p. 212. http://ende.trends.com 0160-9327/03/$ - see front matter q 2003 Elsevier Science Ltd. All rights reserved. doi:10.1016/S0160-9327(03)00065-6 64 Review Endeavour Vol.27 No.2 June 2003 the sort of picture Mendel himself envisaged. Second, as an Box 1. The common picture of Mendelian theory introduction to the study of genetics, it has led to † Mendel observed the inheritance patterns of traits or character- unfortunate and now long-entrenched misunderstandings istics in pea plants, such as height, pod color and or seed shape, of how genes really function, and the relationship between each of which showed alternate forms: tall/short, yellow/green genes and the development of adult traits that has carried and smooth/wrinkled, respectively. over into molecular genetics. † Mendel referred to these alternate conditions as dominant and recessive. † Mendel hypothesized that each trait was represented in the germ Mendel’s background cells of adult plants by two determinants (referred to in his paper Mendel was born on 22 July 1822, in the small rural village as ‘Anlagen’ or ‘elements’), one received from each parent; these of Hyncice, in Moravian Silesia, then part of the Austro– determinants were symbolized by Mendel with a capital letter for Hungarian Empire. As the only son of a peasant farmer, he the dominant form (e.g. A) and a lower-case letter for the recessive was expected to follow in his father’s footsteps and take up form (e.g. a). † The determinants could be combined in one of three ways: two farming. But early on, his interest in natural history and dominants (AA), two recessives (aa) or a dominant and a his studious ways brought him to the attention of the recessive, or hybrid (Aa). priest, Friar Schreiber and the local schoolteacher. In spite † Although he knew nothing about the cytology of chromosomes, of financial hardship for his family, young Johann was sent Mendel hypothesized that in the formation of the pollen or egg cell, the two factors for each trait would separate and go into to a larger school in a nearby village and eventually different gametes; thus a parent that was pure dominant would qualified for Gymnasium in Opava (Troppau). It was a produce gametes all of which contained the dominant factor (A), period of extreme privation, but Mendel managed to and a parent that was pure recessive would produce gametes all of graduate in 1840 with considerable academic success. One which contained the recessive factor (a); hybrid parents, however, of the chief influences on him at the time were Schreiber’s would produce two kinds of gametes: 50% would contain the dominant factor (A) and 50% the recessive factor (a). Enlightenment ideals, particularly his emphasis on † At fertilization, the double-determinant condition would be science as a way of dispelling superstition and ignorance. restored. Schreiber was keenly interested in applying scientific † If both parents were hybrids, any of the three possible combi- principles to improve humanity, and was heavily involved nations could occur and would be distributed randomly, accord- with local agricultural groups and the Pomological ing to the laws of probability: 1 AA:2Aa: 1 aa; because organisms that are Aa and AA look alike, the ratio based on appearance of the Society [5]. traits (what later came to be called ‘phenotype’) would be 3:1. Financial problems continued to plague Mendel as he † When two or more characteristics (e.g. Aa, Tt) are followed in a tried to continue his studies at the Philosophy Institute in dihybrid cross, the two sets of determinants segregate randomly, Olomuc (Olmu¨ tz). After several periods of illness, brought so that any combination of A, a, T and t is possible, what came to be on it is thought by his poverty and overwork, Mendel known as the principle of random assortment. † Factors somehow determine traits, so that after the term ‘gene’ managed to finish his studies at the Institute and entered was introduced in 1909, it was common to speak of a ‘gene for Olomuc University. Here, according to records, he took a tallness’ or a ‘gene for wrinkled seed’. During the early years of the course of lectures in physics, mathematics and logic. Mendelian theory, this was referred to as the ‘unit–character’ However, unable to complete his degree owing to financial hypothesis. † Factors are not modified by being combined with their alternate constraints, he applied for, and was accepted into, the form; thus, the factor, t, for shortness is not affected in any way by Augustinian monastery of St Thomas at Brno (then being combined with the dominant factor, T, for tallness in the Bru¨ nn), Moravia in 1843 (Fig. 2). Although he did not hybrid, a concept that became known as the concept of the ‘purity feel a particularly fervent spiritual calling, Mendel of the gametes’. realized shortly after joining the monastery that at last he was free from constant financial worries and could pursue his intellectual interests in exchange for attending and that observed variations in the patterns of inheritance to pastoral duties.