Gentcis is the name given to the study of heredity, the process by which characteristics are passed from parents to offspring so that all organisms, human beings included, resemble their ancestors. The central concept of genetics is that heredity is controlled by a vast number of factors, called genes, which are discrete physical particles present in all living organisms.
The first geneticists were mainly interested in how genes are transmitted from parents to their offspring during reproduction and how different genes act together to control variable traits such as height and eye colour. A change in emphasis occurred during the 1930s when it was recognized that if genes are physical entities then, like other cell components, they must be made of molecules and it should therfore be possible to study them directly by biophysical and biochemical methods. This led to a new branch of genetics, called molecular biology, which had as one of its initial aims the identification of the chemical nature of the gene. This new approach led to new concept, and soon biologists ceased to regard individual genes simply as units of inheritance and instead began to look on them as units of biological information, with the entire complement of genes in an organism containing the total amount of inforrnation needed to construct a living, functioning example of that organism. The aim of geneticists and molecular biologists over the past 50 years has been to understand the way in which biological information is stored in genes and how that information is made available to the living cell.
Genetics and molecular biology are very closely related subjects, and although there are distinctions between them it is more constructive to treat them as one. For this reason the term molecular genetics is now often used to describe that branch of biology concerned with the study of all aspects of the gene. This text is about moluclar genetics and as such covers some of the most fascinating disoveries and intriguing problems of modern science. However, before describing the discoveries and examining the problems we must first turn our attention to the way in which genetics and molecular biology developed during the late nineteenth and early twentieth centuries. This will set the scene for the subsequent chapters by providing the historical and intellectual backdrop against which our more recent endeavours to understand the gene have been set.
Mendel and the experimental approach to genetics
Genetics as we know it originated with Gregor Mendel, in particular with a paper he published in 1866 in the Verhandlungen des naturforschenden Vereines in Brunn - the Proceedings of the Society of Natural Sciences in Brunn. Mendel was typical of many nineteenthcentury scientists in that he had an insatiable curiosity about the natural and physical world and was keenly interested in the diversity of living things. If Mendel's family had been able to afford for their son an education fitting his intellectual talents then Gregor could very well have risen to become a noted Professor in one of the great European universities. Unfortunately his parents were poor and although Mendel spent four terms at the University of Vienna his education was piecemeal and what he obtained was achieved by perseverance rather than privilege.
It is well known that Mendel joined a monastery near Brno, which was at that time in Austria but is now in the Czech Repulic and evcentually in 1868 became abbot. This choice of career was a fortunate one, because it seems that his duties in the years 1856-1864 were not so onerous as to prevent him carrying out a lengthy series of experiments concerning the inheritance in garden peas of traits as height, flower colour and seed shape. These experiments presented to the Brno Society in papers read by Mendel on 8 February and 8 March 1865 and published the following year in the Societyy Proceedings.
The details of Mendel's experiments and his findings need not concern us at the moment; we will return to them later. But whar should be appreciated at the outset is that Mendel's contribution was not only the basic Laws of Heredity but also the demonstration that heredity could be studied experimentally. Before mendel, and indeed for the remaining 35 years of the nineteenthcentry, concepts about heredity were based almost entirely on simple observations of the living world. The idea that heredity could be studied systematically by straightforward experiments was totally aline to the mainstream of biological thought at that time. Mendel's experiments, which were carefully planned and meticulously executed, demonstrated that heredity works not by some mysterious process but in a predictable and logically consistent manner. His techniques and results provided a clear indication of how the problem of heredity could be unravelled by experimental means. Unfortunately Mendel remained until his death the only person who understood and appreciated the true significance of his work.
The birth of genetics - Mendels rediscovered
The suggestion that Mendel's paper was 'lost' because it was published in an obscure journal by an unknown monk in a remote monastery is not really consistent with the facts. The Proceedings of the Brno Society were fairly well circulated and copies of the 1866 issue containing Mendel's paper were sent to at least 55 European libraires and learned societies, including the Royal Society and Linnean Society in London. Mendel sent reprints of his paper to many of the leading botanists of the day, including Professor Kerner of the Uniniversity of Innsbruck (who evidently did not read it as the reprint was found after his death with the pages still uncut) and Professor Nageli of Munich, with whom Mendel corresponded regularly between 1866 and 1873. Mendel's work was noticed to the extent that he or his paper was mentioned in 16 publications in the late nineteenth century, including the ninth edition of the Encyclopaedia Britannica.The fact is that it was not until 1900 that biological thought had progressed to the point where other biologists could understand the importance of Mendel's work. Mendel was literally 35 years ahead of his time. Eventually in 1900 three botanists, Hugo De Vries, Carl Correns and Erich von Tschermak, each conceived the idea of experiments similar to Mendel's to test their own theories of heredity. Each performed their experiments and then, when studying the litterature before publishing their results, each independently discovered Mendel's paper. After a lengthy gestation the science of genetics was finally born.
Genes, chromosomes and fruit flies
Mendel's experiments, and those of biologists such as De Vries, Correns and Tschermak, removed the mystique from heredity and showed that the process follows predictable rules. These rules can be rationalized as the passage of physical factors, each controlling a separate heritable trait, from the parents to offspring during reproduction. These factors went under a variety of names until 1909 when W. Johannsen proposed the term 'gene' which subsequently entered common usage. By this time it was understood that the genes are carried by the chromosomes of higher organisms, an idea that was prompted by the observation that the transmission of chromosomes during cell division and reproduction exactly parallels the behaviour of genes during these events. The chromosome theory was stated in its most convincing form in 1903 by W.S. Sutton, who at that time was a graduate student at Columbia University in New York and who subsequently became a surgeon before his early death in 1916.
Once the experimental basis of heredity had been established and the chromosome theory accepted, the way was open for a rapid advance in the understanding of genetics. That this advance occurred as rapidly as it did was mainly the result of the intuition and imagination of Thomas Hunt Morgan and the memembers of his research group, notably Calvin Bridges, Arthur Sturtevant and Hermann Muller. Morgan and his colleagues achived something that many biologists dream about: they discovered an organism that was ideally suited for the particular research programme that they wished to carry out. This organism was Droshopila melanogaster, the fruit fly. Drosophila possesses several features that make it very suitable for genetic analysis but most important from Morgan's point of view was the fact that a large number of stable variant forms of the fly could be obtained. The differences between these variants invloves features such as wing shape and body colour, some traits having several different varities. These varities enabled Morgan to investigate the way in which different combination of genes work togeather in controlling the inheritance of an individual characteristic. Morgan's group developed many of the techniques that now have become standard methods in genetic analysis, incuding those that map relative positions of different genes on a chromosome. Between 1911 and 1929 the 'fly-room' at Columbia University provided the data that remain the foundation to our knowledge of the gene as a unit of inheritance.