PERINATAL LESSONS FROM THE PAST
Gregor Mendel, OSA (18221884), founder of scientificgeneticsP M Dunn. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Arch Dis Child Fetal Neonatal Ed 2003;88:F537F539
Gregor Mendel, an Augustinian monk and part-timeschool teacher, undertook a series of brilliant hybridisationexperiments with garden peas between 1857 and 1864 inthe monastery gardens and, using statistical methods forthe first time in biology, established the laws of heredity,thereby establishing the discipline of genetics.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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Correspondence to:Professor Dunn,Department of ChildHealth, University ofBristol, SouthmeadHospital, Southmead,Bristol BS10 5BN, UK;P.M.Dunn@bristol.ac.uk
Accepted 12 June 2003. . . . . . . . . . . . . . . . . . . . . . .
Mendel, baptised Johannes, was born on 22July 1822 at Heinzendorf in Moravia,then part of Austria, now in the Czech
Republic. He was the only son of strugglingpeasant farmers who also had two daughters.Initially Mendel attended the village school inHeinzendorf. There, the parish priest, JohannSchreiber, also an expert in fruit growing,recognised his talents and persuaded his parentsto continue his education in spite of their limitedresources. At the age of 12 he was sent to thegymnasium in Troppau where he studied for thenext six years. During that period, Mendelsfather was incapacitated by a falling log andbecame unable to support his son, whose healthin turn suffered. In 1840 Mendel took a two yearcourse of philosophy at the PhilosophicalInstitute of the University of Olmutz, but havingpassed the final exams in mathematics and Latinphilosophy with the highest grades, he withdrewbecause of ill health. At this point in 1842, hisyounger sister came to his aid with financialsupport while he completed an extra yearsstudy. His exam results were excellent, especiallyin mathematics and physics. In 1843 at the age of21, Mendel entered the Augustinian Order at StThomas Monastery near Brunn (now Brno), tookthe name of Gregor, and began his theologicalstudies at the Episcopal Seminary there. He wasordained to the priesthood in 1847. The role ofthe parish priest at that time in Austria extendedway beyond the care of mens souls. St ThomasMonastery was a centre of creative interest inboth science and culture, having among itsmembers well known philosophers, musicians,mathematicians, mineralogists, and botanists.During this period, Mendel was able to studyagriculture, fruit growing, and viniculture as wellas theology.13
After ordination, Mendel was assigned first topastoral duties, and then, finding himselfunsuited to this because of his shyness, toteaching in a secondary school in Znaim.However, on failing to obtain his teacherscertificate, he was sent to the University of
Vienna (18511853) to study natural sciencesand mathematics. It was at this time that heacquired the scientific research skills that he waslater to put to such good use. In 1854, Mendelreturned to teaching in Brunn but two years lateragain failed to obtain a teaching certificate. It issaid that he withdrew from the exam because ofnervous exhaustion; another account suggeststhat it was because of a disagreement with theexaminers in botany, a disagreement that thenprompted him later to undertake his famousplant breeding experiments. Whatever the truth,this exam failure led to Mendel becoming a part-time assistant teacher, a post that provided himwith plenty of time to undertake his scientificresearch13 (fig 1).
Between 1857 and 1864 Mendel undertook aseries of hybridisation experiments in theMonasterys garden, which were breathtakingfor their brilliance in planning, observation, andanalysis, and in interpretation of results. He wasfortunate to choose the garden pea, Pisum, for hisstudies because it exists in separate pure lines.Within each line, each plant is identical,although each may vary in characters such ascolour or shape. In addition, peas are hermaph-rodite, bearing both male and female sex cells onthe same individual and able to self fertilise.Furthermore, the flowers are naturally selffertilised before the bud opens and thus beforeinsects can intervene in the process. In addition,the pea is an annual and great numbers can begrown in a small space. Mendel described hisproject in the following way in the introductionto his paper on Experiments in plant hybridization,which was presented to the Society for the Studyof the Natural Sciences in Brunn in 186514
Experiments in plant hybridization5
Experience of artificial fertilization, such asis effected with ornamental plants in order toobtain new variations in colour, had led tothe experiments which will here be discussed.The striking regularity with which the samehybrid forms always reappeared wheneverfertilization took place between the samespecies induced further experiments to beundertaken, the object of which was to followup the developments of the hybrids in theirprogeny so far, no generally applicablelaw governing the formation and develop-ment of hybrids has been successfully for-mulated of
Those who survey the work done in this department willarrive at the conviction that among all the numerousexperiments made, not one has been carried out to suchan extent and in such a way as to make it possible todetermine the number of different forms under which theoffsping of hybrids appear, or to arrange these forms withcertainty according to their separate generations, ordefinitely to ascertain their statistical relations.
It requires indeed some courage to undertake a labour ofsuch far-reaching extent; this appears, however, to be theonly right way by which we can finally reach the solutionof a question the importance of which cannot be over-estimated in connexion with the history of the evolution oforganic forms.
The paper now presented records the results of such adetailed experiment. This experiment was practicallyconfined to a small plant group, and is now, after eightyears pursuit, concluded in all essentials. Whether theplan upon which the separate experiments were con-ducted and carried out was the best suited to attain thedesired end is left to the friendly decision of the reader.
This research did indeed require courage and also persistenceand meticulous record keeping. In all, some 10 000 plantswere grown and observed during the eight year study. Thefollowing further extracts from his paper published in 1866provide a taste of his style and conclusions.5
The forms of the hybrids5
In the case of each of the seven crosses the hybrid-character resembles that of one of the parental forms soclosely that the other either escapes observation comple-tely or cannot be detected with certainty. This circumstance
is of great importance in the determination and classifica-tion of the forms under which the offspring of the hybridsappear. Henceforth in this paper those characters whichare transmitted entire, or almost unchanged in thehybridization, and therefore in themselves constitute thecharacters of the hybrid, are termed the dominant, andthose which become latent in the process recessive. Theexpression recessive had been chosen because thecharacters thereby designated withdraw or entirelydisappear in the hybrids, but nevertheless reappearunchanged in their progeny, as will be demonstrated lateron.
It was furthermore shown by the whole of the experimentsthat it is perfectly immaterial whether the dominantcharacter belongs to the seed-bearer or to the pollen-parent; the form of the hybrid remains identical in bothcases
The first generation (bred) from the hybrids5
In this generation there reappear, together with thedominant characters, also the recessive ones with theirpeculiarities fully developed, and this occurs in thedefinitely expressed average proportion of three to one,so that among each four plants of this generation threedisplay the dominant character and one the recessive. Thisrelates without exception to all the characters which wereinvestigated in the experiments. The angular wrinkled formof the seed, the green colour of the albumen, the whitecolour of the seed-coats and the flowers, the constrictionsof the pods, the yellow colour of the unripe pod, of thestalk, of the calyx, and of the leaf venation, the umbel-likeform of the inflorescent, and the dwarfed stem, allreappear in the numerical proportion given, without anyessential alteration. Transitional forms were not observedin any experiment.
Since the members of the first generation spring directlyfrom the seed of the hybrids, it is now clear that the hybridsform seeds having one or other of the two differentiatingcharacters, and of these one-half develop again the hybridform, while the other half yield plants which remain
Figure 1 Gregor Mendel, 18221884.
Figure 2 The opening paragraph of Mendels 1865 paper on thehybridisation of peas.
constant and receive the dominant or the recessivecharacters (respectively) in equal numbers.
Before Mendel, heredity had been regarded as a blendingprocess and the offspring a dilution of the various parentalcharacteristics. Mendel showed that the different charactersin heredity followed specific laws, which could be determinedby counting the diverse kinds of offspring produced fromparticular sets of crosses. He established two principles ofheredity now known as the law of segregation and the law ofindependent assortment, thereby proving the existence ofpaired elementary units of heredity (genes) and establishingthe statistical laws governing them. In summary, Mendelshowed that inheritance depended on the combination oftwo unequally expressed genes which combined in anindividual but never blended. In doing so, he was the firstto apply a knowledge of mathematics and statistics to abiological problem.
Although copies of the Proceedings containing Mendelspublication were sent to 133 associations of natural scientistsand libraries in a number of countries, and he himself sentreprints to scholars and friends around Europe, there wereonly three citations of his work in the scientific literatureduring the next 35 years. Mendel in fact paid the price forbeing too far in advance of his time.
In 1868, the Abbot of St Thomas died and Mendel at theage of 46 was elected to succeed him as spiritual director ofthe monastic community. He was clearly well liked andrespected by his fellow monks for his honesty, loyalty, andmodesty. However, from that time on he was overwhelmedby administrative and public service duties. In particular, hebecame very involved in fighting, unsuccessfully, thegovernment on a new law to tax the monastery. In addition,he became a member of the Moravian legislature and wasgreatly in demand in numerous fields, religious, literary,agricultural, horticultural, humanitarian, and educational.Among the 34 societies of which he was an active memberwere the Austrian Zoological-Botanical Society, the AustrianMeteorological Society, the Moravian Apiary Society, and theImperial-Royal Moravian-Silesian Agricultural Society. Atabout this time he also developed backache, his eyesightbegan to fail, and he became overweight. He published onlyone further scientific paper, on hawkweed in 1869. It was oflittle significance. In his own words he had to neglectcompletely his experimental work with plants. He became arather solitary figure. Towards the end of his career he wrote:I have experienced many a bitter hour in my life.Nevertheless, I admit gratefully that the beautiful, goodhours far outnumbered the others. My scientific workbrought me such satisfaction, and I am convinced the entire
world will recognise the results of these studies. The worldmight, but first there were to be those 35 years of neglect.Only in 1900 did three botanists, Hugo de Vries (Holland),Karl Correns (Germany), and von Tschermac (Austria),independently confirm his work. Meanwhile Francis Galtonhad in 1897 arrived at a statistical law of heredity based onobservations on the pedigrees of Basset hounds. Even at theturn of the century, the recognition of Mendels work arouseda storm of controversy, which lasted a further 35 years.Mendels use of statistics in biology was original and arousedfeelings of intense hostility in certain quarters. There wereeven accusations that he had been guilty of falsifying hisdata. By the 1930s, however, the brilliance and correctness ofhis observations and conclusions on hereditary transmissionwere universally accepted.
Mendel passed away after a long and painful illness on 6January 1884. He was 62. Postmortem examination con-firmed Brights disease with secondary hypertrophy of theheart. So died the Right Reverend Abbot Gregor JohannMendel, mitred prelate and companion of the Royal andImperial Order of Francis Joseph. He was laid to rest in theBrunn central cemetery. The world has indeed come torecognise him as one of the greatest scientific biologists of alltime and the father of genetics.
ENVOIDeoxyribonucleic acid (DNA) was identified in 1871. Seventythree years later, Oswald Avery showed that Mendelsparticles or genes were entirely made up of this substance.Fifty years ago in 1953 Francis Crick and James Watsonannounced their discovery of the double helix structure ofDNA, which allows the molecule to replicate and hence laydown the blueprint for living organisms and plants. Thisdiscovery revolutionised science and gave a great boost to thenew discipline of molecular biology. It has led to the HumanGenome Project, to genetic screening, to genetic engineering,and to genetic fingerprinting. From the viewpoint of perinatalmedicine, it has given rise to the prospect of prenatal geneticdiagnosis and gene therapy.
REFERENCES1 Weiling F. Historical study: Johann Gregor Mendel, 18221884. Am J Med
Genet 1991;40:125.2 Sorsby A. Gregor Mendel. BMJ 1965;i:3338.3 Walsh RJ. Mendel, man and medicine. Med J Austr 1966;2:917.4 Jones S. In the blood: God, genes and destiny. London: Flamingo,
1996:1819.5 Mendel G. Versuche uber Pflanzen-Hybriden. Transactions of Verhandlungen
des naturforschenden Vereines in Brunn (1865) 1866;iv:3270, [Extractsrepublished. BMJ 1965;i36774.].
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