Robert Olby. New Dictionary of the History of Ideas. Editor: Maryanne Cline Horowitz. Volume 2. Detroit: Charles Scribner’s Sons, 2005.
Genetics as a discipline is young, but the concept that forms its subject—inheritance—stretches back in time. The word has been formed from the adjective genetic, found in the sciences of the nineteenth and twentieth centuries—for example, biogenetic law, genetic affinity, genetic psychology—and meaning, according to the Oxford English Dictionary,”pertaining to, or having references to, origin.” Not until 1906 was the noun genetics publicly proposed to cover those labors that, in the words of its author, William Bateson, “are devoted to the elucidation of the phenomena of heredity and variation: in other words to the physiology of descent, with implied bearing on the theoretical problems of the evolutionist and the systematist, and application to the practical problems of breeders, whether of animals or plants.”
We begin, therefore, by commenting briefly on the long history of notions of heredity and variation, reflecting the while on the significance of cultural and economic factors that both drew attention to them and shaped them. Next we turn to the father figure of genetics, Gregor Mendel (1822-1884), and his introduction of the Mendelian experiment. With the rediscovery of his work in 1900 we explore the contribution of the early “Mendelians,” the melding of Mendelian heredity with the theory of the chromosome, a synthesis that revealed a geography of heredity in the cell but did not answer the question, “What is the identity of the genetic material?” Only with the introduction of the Watson-Crick structure for DNA in 1953 was a window opened through which to glimpse the terrain that was to become “molecular genetics.”
Heredity and variation are today considered as two sides of the same coin. Thus variation among sibs results from the varied commingling and expression of the hereditary determinants from two parents. Spontaneous changes in the hereditary material (mutations) give rise to variations, and these are inherited. In other words there is heredity, variation, and the heredity of variation, and they belong together. Prior to the latter half of the nineteenth century this conceptual framework did not exist. There still lingered relics of the ancient view of heredity as the result of the reproduction of the type, whereas any deviance from the type was ascribed to the effects of the mother’s imagination, changed conditions of life, and so on. Moreover both heredity and variation were situated within the broad topic of “generation.” This included the regeneration of lost and damaged organs, the development of the embryo from the fertilized egg, and all forms of reproduction, both sexual and asexual. But as attention directed to human heredity increased during the nineteenth century the subject of the transmission of hereditary characters began to acquire a separate conceptual status.
In the eighteenth century two rival conceptions of the phenomenon of inheritance were in play: the doctrine of preformation claimed that like generates like because the offspring are in some way already present in the germ and have only to unfold or “evolve” to yield offspring like the parents. A literal view of this doctrine was held by some who claimed that hidden miniatures of future generations must have existed from the time of creation, all nested one within another, like a set of Russian dolls, hence the term preexistence for this version of the doctrine. Procreation became, as it were, the act of revealing what had been created long before. Opposed to this was the doctrine of epigenesis, according to which the parts of the offspring are formed successively, and in the process the embryo undergoes a series of transformations. Support for this view came from descriptions of the development of the fertilized egg. Experimental support came also from the hybridization experiments of Joseph Kölreuter, who in 1766 described how he had succeeded in transforming one species of plant into another. How, he asked, was this possible if the offspring is already preformed? He also found that no matter which parent supplied the “male seed” (pollen) and which the female “seed” (ovules), the resulting hybrids were the same. How could these results be accounted for on the basis of any theory of preformation—whether, as the animalculists claimed, the preformed miniatures reside in the spermatozoa, or as the ovists urged, in the egg? A further difficulty arose for preformationists when nineteenth-century microscopists developed a cell theory according to which the fundamental unit of life is the cell, not some preformed rudiments of the organism.
These two resources—hybridization and the cell theory—were to form the basis for Gregor Mendel’s research. Prior to his work, however, the study of hybridization had been carried out under different assumptions and in a much more limited manner. The number of hybrid offspring grown in an experiment was limited, and the prevalence of the effect of hybridization in diluting character differences supported the view that heredity is a blending process, like the mixing of ink and water. The conception of the organism too was generally holistic: that is, the type of the species acts as a whole, its “essential” characteristics—flower color, habit, leaf shape, and so on—being but expressions of the type. With this point of view, effective analysis of hereditary transmission is impossible.
Gregor Johann Mendel
Raised on a farm in rural Heinzendorf in German-speaking Silesia, the young Johann, as he was christened, had an early education in the practical aspects of horticulture and agriculture before he left home to attend a gymnasium and at eighteen years of age entered the University of Olmütz. The stress of inadequate finances there led him to apply in 1843 to the Augustinian monastery in Brünn, the industrial and economic capital of Moravia. It was there that, supported by the wise and understanding abbot Cyril Napp, he was encouraged to institute experiments analyzing the phenomenon of hybridization. The subject was of concern to the monastery, with its extensive agricultural holdings in Moravia, a region known for its sheep and wine. Also thanks to the abbot, Mendel had spent two years at Vienna University, studying principally physics, botany, and zoology. There he had learned about the cell theory, according to which the organism is composed neither of a continuous fabric like lacework nor of a multitude of globules but of individual vesicles or cells, all formed by division of preexisting cells that can be traced back to the foundation cell or fertilized egg, this having arisen by fertilization of the egg cell by one pollen cell.
The experiments that led to his well-known theory began with the testing of thirty-four varieties of the edible pea (Pisum) followed by eight years of hybridization (1856-1863). Taking seven traits, he followed the hereditary transmission of each. The scale of the research was unprecedented, the size of his progeny populations being such that clear statistical regularities emerged. It was not just that he noted the separate behavior of the seven traits he studied, nor that there was a marked difference between the population sizes of those carrying the two contrasted characters, but that they approximated to the ratio 3:1. Thus for the trait seed color, Mendel harvested 6,022 green seeds and 2,001 yellow from his hybrid progeny, offering the most striking example among his seven traits of a 3:1 ratio. Further research revealed that two-thirds of the larger class did not breed true and the other third did. Thus the ratio 3:1 was really constituted of three classes in the ratio 1:2:1.
As a physicist trained in combinatorial mathematics this ratio reminded him of the binomial equation (A a) 2 1 A22 Aa 1a 2. Using A and a to represent the potential carried in the pollen cell and in the egg cell, and knowing that A obscures (is dominant over) a, this expansion appears as 3 A 1 a. Well-grounded in cytology, he suggested that the differing elements brought together in the hybrid remain together until the germ cells are formed. Then they separate and pass into separate germ cells. There result, he declared, “as many sorts of egg and pollen cells as there are combinations possible of formative elements.” These claims—known as “germinal segregation” and the “independent assortment” of characters—he supported from his crossing of plants differing in two and in three traits. These two principles were later to be called Mendel’s two laws.
Mendel’s work did not meet with an enthusiastic response because it was opposed to several securely held beliefs. All the traits he included in the data concerned nonblending characters, but the consensus was that blending is the rule and that the agreed representation of heredity is in terms of fractions: one-half being from the two parents, one-quarter from the four grandparents, and so on, implying that no contribution is entirely lost but that there is a repeated dilution of differences in reproduction. Mendel’s theory denied this, for in his theory, after segregation, the elements in question would either be present or absent in a given pollen cell or egg cell, and it would be a question of chance as to which elements finished up in the foundation cell of the offspring.
His paper was directed to two specific questions: First, whether hybridization can lead to the multiplication of species; and second, what part hybridization plays in the production of variation. On the first of these he was clear that Pisum does not yield constant hybrids—that is, hybrids that breed true, reproducing the hybrid form like a pure species. Therefore he instituted experiments with other species to test the general validity of his results. As to the second question, he explained how the variation following hybridization can be understood as the result of the recombination of independently transmitted characters brought together in the hybrid. Therefore he opposed those who, like Darwin, attributed such variation ultimately to the act of bringing together species that have been exposed to different conditions of life. Those who claimed, like Darwin, that cultivated plants are more variable than wild ones due to their changed conditions of life, he also strongly opposed.
In 1900 three European botanists, Hugo de Vries, Carl Correns, and Erik Tschermak, published the results of their experiments carried out in the 1890s that supported Mendel’s experimental results and his conclusions. Although the first two had in fact seen Mendel’s paper earlier, its significance had not struck them. Only later, when they had their own results, did they encounter his paper again and realize its importance. In England the Cambridge zoologist William Bateson teamed up with the Reverend William Wilks, secretary of the Royal Horticultural Society, and Maxwell Masters, chairman of the society’s scientific committee, to spread the word about Mendel. Through this prestigious and influential society Bateson introduced Mendel’s work to the English-speaking world, and the Reverend Wilks asked Charles Druery, a hybridist and fellow of the society, to translate Mendel’s paper into English for its publication in the society’s journal.
It was at the Royal Horticultural Society’s Third International Conference on Hybridisation and Cross-breeding that Bateson introduced the term “genetics” to the audience gathered in London in 1906. When the conference proceedings appeared Wilks had renamed it Report of the Third International Conference 1906 on Genetics: Hybridization.
British biologists were for the most part unreceptive to Mendel’s work. Karl Pearson, upholder of Galton’s biometric tradition, was opposed. Darwinians like Alfred Russel Wallace were appalled, and the Oxford professor Edward B. Poulton reported the consensus he had found among eminent zoologists that Mendelian writings were “injurious to Biological Science, and a hindrance in the attempt to solve the problem of evolution.” According to Pearson, the Mendelian theory was not conformable with the statistical data he was amassing on the relation between successive generations (the regression coefficients). It took the insight and persistence of the young Ronald Aylmer Fisher (1890-1962) to remove this roadblock to the integration of Mendelism and biometry. His solution of the problem finally appeared in 1918.
The biometricians’ theory was ancestrian, meaning that the hereditary constitution of offspring was considered to be a collection of representations from the ancestors, the proportions of which are based on some form of the old fractional theory. This was formulated under the title “The Ancestral Law of Inheritance.” Confining their attention to what is visible, the biometricians were not concerned with so-called hidden elements. As a positivist, Karl Pearson was particularly concerned not to invent or invoke unobservable entities like Mendelian factors. Mendelians, by contrast, were opening up the space between the hereditary determinant (Mendelian factor) and the observable character or characters for which it is responsible. Mendel’s language of the transmission of characters was giving place to the Mendelians’ growing reference to the transmission of factors.
Powerful opposition to the biometricians came not only from Bateson in England but from Wilhelm Johannsen in Denmark. He complained that the biometric approach was based on the assumption that the “personal qualities” of an individual “are the true heritable elements or traits.” But this, he declared, “is the most naïve and oldest conception of heredity” and can be traced back to Hippocrates. It was, he claimed, borrowed from the legal language of inheritance and heirs to property. As such it includes not only long-standing possessions but what has been acquired by the testator in his or her lifetime. But in biology the evidence was against acquired characters being heritable, and the modern view of heredity was that the “sexual substances” in the egg and sperm determine the personal qualities of the individual, not the reverse. To banish these confusions Johannsen proposed a new language for heredity in the form of the “gene,” “genotype,” and “phenotype.” “The gene,” he explained, “is nothing but a very applicable little word, easily combined with others, and hence it may be useful as an expression for the ‘unit-factors,’ ‘elements,’ or ‘allelomorphs’ in the gametes, demonstrated by modern Mendelian researchers. A ‘genotype’ is the sum total of all the ‘genes'” in a germ cell or fertilized egg. Avoiding speculation as to the nature of the gene, he felt that “the terms ‘gene’ and ‘genotype’ will prejudice nothing” (Johannsen, p. 133). But just as it took a long time for the term genetics to become generally established, so was the case for Johannsen’s terms.
The Chromosome Theory of Heredity
Meanwhile, in America a bridge between zoology and Mendelism was being constructed at Columbia University, New York City. There, Edward Beecher Wilson was promoting the search for parallels between Mendelian heredity and the theory of the chromosome. Subsequently the embryologist Thomas Hunt Morgan, studying the determination of sex and the hereditary transmission of mutations in the fruit fly (Drosophila), discovered what he called “sex-limited” inheritance, and in 1911 he associated it with a specific chromosome. This led in 1915 to his groundbreaking text The Mechanism of Mendelian Heredity, which he coauthored with the three young men working under him: Alfred Henry Sturtevant, Hermann Joseph Muller, and Calvin Bridges. Here the authors distanced themselves from any suggestion that the factorial hypothesis (“gene” hypothesis) can account for the embryological development of the hereditary characters. A whole mysterious world, they explained, lies between the factor and the character. So they challenged the claim that “until we know something of the reactions that transform the egg into the adult” our hereditary theories “must remain superficial.” The Mendelian theory, they argued, does not explain development, nor does it pretend to. Yet “it stands as a scientific explanation of heredity, because it fulfills all the requirements of any causal explanation” (Morgan, p. 280).
Here the authors were seeking to separate genetics from embryology. At the same time, they were developing its relation with the cytologists’ study of the chromosomes. This association had at first seemed improbable since many organisms were known to have very few chromosomes—Pisum has seven pairs, the fruit fly four, and the horse thread worm (Parascaris) only two. Assuming the Mendelian factors for the numerous hereditary factors are able to recombine in all possible combinations, as Mendel claimed, surely they could not be tied together on just a few chromosomes. Fortunately in 1909 F. A. Janssens in Belgium had observed “cross-over” patterns between chromosomes that he called “chiasmata,” a discovery that gave Morgan the idea that chromosomes might exchange parts, thus permitting recombination. This insight was followed by Sturtevant’s suggestion that the frequency of such recombinations between factors could be used as a measure of the distance separating them along the chromosome, and the mapping of genes became a reality. Already the simple picture of Mendelian heredity had been complicated by the discovery of interaction between factors, association of factors (linkage), and the determination of a character by many factors (polygenic inheritance). The latter brought blending heredity under the explanatory arm of Mendelian heredity. The degree of blending was determined by the number of genes involved. Ancestral inheritance was absorbed into Mendelian heredity. What had once been likened to fluids mixing was now attributed to a finite and fixed number of Mendelian factors.
Culture of Heredity
Alongside the developing experimental tradition of the biologists, the nineteenth century saw increasing attention given to family histories (genealogy) and to population studies (biometry). Both owed their popularity to the growing concerns about human heredity. Was increasing urbanization affecting the quality of human heredity as evidenced by the increasing numbers of the insane, the tubercular, the alcoholic? Supporting this concern was the medical concept of a diathesis—that is, the predisposing to certain diseases, especially those chronic conditions like gout, epilepsy, asthma, tuberculosis, and cancer, that are often manifested later in life. Diatheses were judged to be features of a person’s hereditary constitution. Although the tuberculous diathesis was not banished by Robert Koch’s isolation of the tubercle bacillus in 1882, it did become transformed into the genetic susceptibility to the pathogen.
Genealogy became of special interest for several reasons. Many an aspiring family in Napoleonic Europe, wishing to claim the status of majorat (Napoleon I’s substitute for aristocracy), needed to provide their family genealogies as evidence of the fraction of “blue blood” in their ancestry. In Jamaica the fractional theory was used to draw the line between those descended from mulattos who could and could not be considered white. Hence the classification: mulatto, half black; terceron, one-quarter; quateron, one-eighth; quinteron, one-sixteenth. In England, Francis Galton, concerned about what he saw as a growing mediocrity in urban populations, used genealogy to argue for the inheritance of what he called “genius”—exceptional ability that is inborn. Such he found in families like the Bachs, Bernoullis, and Darwins and thought to find especially among judges. In the early years of the twentieth century, with the advent of Mendelism, the hunt for pedigrees that exemplified Mendelian heredity was all the rage. Hereditary night blindness offered the most extensive pedigree, but many were the studies of the familial incidence of feeblemindedness, inebriation, epilepsy, pauperism, and criminality. Concerns about degeneration of the European races, and the felt need to apply science to the problem, provided a political climate in which Galton decided in 1904 he could launch his bid for the science he had earlier (1883) called “eugenics” and defined as “the science of improving the stock … which, especially in the case of man, takes cognizance of all the influences that tend in however remote a degree to give to the more suitable races or strains of blood, a better chance of prevailing speedily over the less suitable than they otherwise would have” (Human Faculty, p. 17).
The stark hereditarian leaning of Galton did not go un-challenged. His first book, Hereditary Genius (1869), received mixed reviews, the accuracy of his biographical data coming under fire. In Switzerland, Alphonse de Candolle argued persuasively for the effects of the educational, cultural, and political climate, rather than heredity, to account for the remarkably high representation of Swiss scientists among foreign members of the Royal Society and the Académie des Sciences. In this way de Candolle countered the emphasis Galton had placed on heredity in his work English Men of Science (1874). As for the enthusiasts for eugenics, both those in the biometric tradition of Galton and the experimental tradition of Mendel were for the most part supportive. One Mendelian who adopted a more cautious position was William Bateson. Though an elitist, he judged the scientific basis of many of the eugenists’ claims inadequate and kept his group of coworkers at a distance from the eugenically inspired Mendel Society that had formed in England during the early years of Mendelism. As an hereditarian, of course, Bateson was concerned that those carrying harmful genes should be discouraged from bearing offspring. He was thus a supporter of negative eugenics. But as to positive eugenics—the encouraging of selected individuals to mate and have offspring—he was not clear what particular traits should be looked for.
Fine Structure of the Gene
Morgan’s introduction of the fruit fly to genetics revolutionized it because the fly’s rapid life cycle and minute size enabled the scale of experimentation to be markedly increased. Contrast the whole year required between generations of peas and corn with the two weeks needed for the fruit fly. This meant that in a short time over a hundred characters had been studied and many mutants found. Drosophila became as a result the most prominent “model organism” of genetics. Bridges oversaw and maintained the growing stock of the mutant types and made them freely available internationally. The lab at Columbia, known as the “Fly Room,” was an example of team effort, led by a genial, exuberant boss. Morgan had to undergo quite a conversion by his team, but the outcome was a giant step forward in genetics, crowned with the award of the Nobel Prize in 1933.
H. J. Muller was less close to Morgan than the others and did not long remain in the group. Their views on genetics differed. Whereas Morgan was happy to leave to one side the question of the material basis of the gene, Muller wanted to know the answer. His pioneer work on the production of mutations by X rays not only won him the Nobel Prize but offered him the hope of establishing the size of the gene. This approach was used by the brilliant Russian geneticist N. V. Timoféeff-Ressovsky, in Germany, to yield an estimate of the “sensitive volume” of the gene as that space needed by one thousand atoms, or about the size of an average protein. Unfortunately, as later work revealed, the methodology and interpretation of this experiment proved faulty.
Drosophila was by no means the only model organism for genetics. In addition to commercial cereal crops, poultry, mice, and yeast, the bread mold Neurospora figures prominently in the development of the field. Using this organism, George Beadle and Edward Tatum concluded that there is a 1:1 relation between a gene and a given enzyme, thus suggesting that the primary product of a gene is an enzyme. But for the fine structure analysis of the gene the model system that was to bring the analysis down to the molecular level was the viral infected colon bacillus (Escherichia coli). Here the bacterial virus (bacteriophage, or phage) has just one chromosome, and in mixed infections this chromosome can recombine with one from another, thus permitting recombination and making fine structure mapping possible. By 1957 Seymour Benzer had used this system to make an estimate of the likelihood of crossing-over between two mutants one DNA base apart in the bacteriophage T4 to be 1 in 10,000. His own analysis had then reached 1 in 20,000.
The period covering the first half of the twentieth century is often referred to as “classical genetics.” Morgan had set the tone, treating the gene as an abstraction and the Mendelian analysis of experimental data as an algorithm. But as early as 1922 Muller had drawn the analogy between bacterial viruses and genes and glimpsed the possibility of grinding “genes in a mortar” and cooking them “in a beaker.” There existed too a continuing concern during this period to identify gene products chemically, working with flower pigments in plants and eye pigments in insects. Nonetheless, the chemical constitution of the gene remained vague, and geneticists were content to assume it was a protein of a special kind: one that can both catalyze its own reproduction (autocatalysis) and provide an enzyme that catalyzes a quite different reaction in the general metabolism of the cell (heterocatalysis.)
The protein nature of the gene was called into question in 1944 when three Rockefeller scientists, Ostwald Avery, Colin MacLeod, and Maclyn McCarty, published their identification of the so-called transforming principle as deoxyribonucleic acid (DNA). This principle, obtained from dead bacterial cells of one strain, was shown to transfer a characteristic from that strain to another strain. This extract contained only the minutest traces of protein; the rest was DNA. Geneticists knew about this work, but the majority assumed that the DNA was acting as a mutagen, altering the genetic constitution of the recipient cell, not transferring a gene. Evidence from other quarters was needed to shift the status quo. It came from the cytochemists and the phage biologists. The former discovered the correlation between the quantity of DNA in the nucleus and the number of chromosomes. Germ cells had half the content of body cells. Cells containing multiple sets of chromosomes (polyploids) had correspondingly raised DNA content. The same was not true of protein.
Phage biologists did not achieve as clean a transfer of DNA in their work as had Avery in his, but they were able to separate the functions of the protein and the nucleic acid of the phage particle, assigning the protein to the task of attaching to the host and causing it to burst (lyse), whereas the nucleic acid finds its way into the host and is used to constitute the progeny phage particles. By 1952 Alfred Hershey and Martha Chase at Cold Spring Harbor Laboratory could show that 85 percent of the parental DNA is present in the progeny particles. This result had an impact because of the visual evidence previously provided by the electron microscope of the sperm-like particles and their “ghosts” empty, their DNA contents removed.
Making the case for DNA acting as the repository of the genetic specificities of the organism called for establishing the kind of structure DNA possesses that would permit it to function thus. Known to be a long-chain molecule, its backbone composed of sugar rings attached to one another by phosphate arms, it has only four kinds of side-groups attached to the sugars—the bases adenine, guanine, thymine, and cytosine. This contrasts unfavorably with the proteins, for they have twenty different amino acids that can be arranged in countless different sequences.
The proposal of the double-helical model of DNA by James Watson and Francis Crick in 1953 overcame this difficulty because their structure, a cylindrical one with the four kinds of bases packed inside the two helically entwined sugar-phosphate backbones, permits any kind of sequence of the bases. Moreover, these bases are paired by weak bonds across from one base to its opposite number, adenine with thymine, guanine with cytosine. Watson and Crick therefore visualized the duplication of the gene as the result of separating the two chains of the parent double helix and attaching free bases to those now unpaired in accordance with the above complementary relations.
The work of Rosalind Franklin and Maurice Wilkins in London had not only aided Watson and Crick in devising their proposed structure, but when published alongside it offered crucial support. Yet it was not until 1958 that evidence from quite different approaches was published confirming predictions made from the model. Only then did interest in the structure become widespread. In genetics the work of Sydney Brenner, Francis Crick, Leslie Barnett, and R. J. Watts-Tobin, using mutagenesis in bacteriophage to establish the general nature of the genetic code, was published in 1961. It marked a success in applying the genetic approach to questions at the molecular level, for they showed that the genetic message is composed of triplets of bases, read from a fixed starting point, in only one direction, and without commas between the triplets. Meanwhile biochemists had been establishing the identity of the amino acids coded by given triplet sequences of bases.
It was the physicist George Gamow who had first suggested a DNA code for the amino acids in proteins. He had hoped the right code could be established by mathematical reasoning but had to accept that nature does not use the most mathematically elegant solution. The amino acid sequences being discovered in proteins showed no limitations on the permutations of nearest neighbors of the kinds required by these mathematical codes. Hence the need to turn to the biochemists and the geneticists to solve the problem. They attacked it with vigor, and by 1966 the full details of the code were established. But the major transformation of genetics came with the introduction in the 1970s of the techniques of recombinant DNA technology that made directed manipulation of the genetic material possible.
The Molecular Gene
It has been remarked that molecularizing the gene, far from establishing it as a discrete entity, had the opposite effect, fragmenting and destroying it. True, ever since the 1930s there had been discussion of what was euphemistically called “position effect”—the idea that a gene defined by its function can suffer two distinct mutations and that even if one normal example of the two mutated sites is present in the cell, the gene will only function when both lie on the same chromosome. The neat coincidence between the gene defined by function, by location, and by mutation was broken in these cases. But unraveling the mystery of protein synthesis, in which the function of the genes is to specify which amino acids are to be incorporated into the protein and in what order, revealed further complexity. It turned out that the genetic message (messenger RNA) from many genes is cut into parts, some fragments being rejected (known as introns) and the remainder (exons) incorporated into the chain that is transcribed into a sequence of amino acids. Different parts of the same message may thus be incorporated into different gene products. To those working in the field, these complexities are par for the course. The word gene has not died and been buried, but the context in which it is used tells the informed listener in what sense to understand the term. The simple conception of the Mendelian factor or gene of classical genetics has surely suffered a major series of revisions. The simple picture of genes like beads on a string, though essential to get a hand-hold on the problem, has not survived. But the early claim of Richard Goldschmidt that any discreteness of the gene be dropped, and that the chromo-some be considered one continuous developmental unit, has never been accepted. There are codons in the DNA for starting and terminating the genetic message. Genes are interspersed with non-coding regions in the DNA. But the relation between the DNA and the proteins around it is a subtle and dynamic one.
Since Johannsen introduced the term “gene” first in 1909 it has served as a flexible concept, suffering many revisions and acquiring many meanings. In the process the extreme hereditarian view of DNA as dictating the life of the cell has been undermined by the discovery of a hierarchy of interactions between DNA and proteins. Genetics has in truth found its place at the core of biology, and in doing so it has revealed a machinery of the cell more intricate and subtle than could ever have been imagined.