The History of Genetics - Genetics At The Dawn Of Thetwentieth Century

During the years following Mendel's work, understanding of cell division and fertilization increased, as did insight into the component parts of cells known as subcellular structures. For example, in 1869 the Swiss biochemist Johann Friedrich Miescher (1844–95) looked at pus he had scraped from the dressings of soldiers wounded in the Crimean War (1853–56). In the white blood cells from the pus, and later in salmon sperm, he identified a substance he called nuclein. In 1874 Miescher separated nuclein into a protein and an acid, and it was renamed nucleic acid. He proposed that it was the "chemical agent of fertilization."

In 1900 three scientists—Karl Correns (1864–1933), Hugo de Vries (1848–1935), and Erich Tschermak von Seysenegg (1871–1962)—independently rediscovered and verified Mendel's principles of heredity, and Mendel's contributions to modern genetics were finally acknowledged. In 1902 Sir Archibald Garrod (1857–1936), an English physician and chemist, applied Mendel's principles and identified the first human disease attributable to genetic causes, which he termed "inborn errors of metabolism." The disease was alkaptonuria, a condition in which an abnormal buildup of an acid (homogentisic acid or alkapton) accumulates.

Seven years later, Garrod published Inborn Errors of Metabolism, a textbook describing various disorders that he believed were caused by these inborn metabolic errors. These included albinism (a pigment disorder in which affected individuals have abnormally pale skin, hair, and eyes) and porphyria (a group of disorders resulting from abnormalities in the production of heme, a vitally important substance that carries oxygen in the blood, bone, liver, and other tissues). Garrod's was the first effort to distinguish diseases caused by bacteria from those attributable to genetically programmed enzyme deficiencies that interfered with normal metabolism.

In 1905 the English geneticist William Bateson (1861–1926) coined the term "genetics," along with other descriptive terms used in modern genetics, including "allele" (a particular form of a gene), "zygote" (a fertilized egg), "homozygote" (an individual with genetic information that contains two identical forms of a gene), and "heterozygote" (an individual with two different forms of a particular gene). Arguably, his more important contributions to the progress of genetics were his translations of Mendel's work from German to English and his vigorous endorsement and promotion of Mendel's principles.

In 1908 English mathematician Godfrey Hardy (1877–1947) and German physician Wilhelm Weinberg (1862–1937) independently developed a mathematical formula that describes the actions of genes in populations. Their assumptions that algebraic formulas could be used to analyze the occurrence of, and reasons for, genetic variation became known as the Hardy-Weinberg Equilibrium. It advanced the application of Mendel's laws of heredity from individuals to populations, and by applying Mendelian genetics to Darwin's theory of evolution, it improved geneticists' understanding of the origin of mutations and how natural selection gives rise to hereditary adaptations. The Hardy-Weinberg Equilibrium enables present-day geneticists to determine whether evolution is occurring in populations.

The Chromosome Theory of Inheritance

Bateson is often cited for having said, "Treasure your exceptions." I believe Sturtevant's admonition would be, "Analyze your exceptions.…"

—E. B. Lewis, "Remembering Sturtevant," Genetics, vol. 141, 1995

American physician and biologist Walter Sutton (1866–1916) conducted studies using grasshoppers (Brachystola magna) he collected at his family's farm. Sutton was strongly influenced by reading Bateson's work and sought to clarify the role of the chromosomes in sexual reproduction. The results of his research, published in 1902, demonstrated that chromosomes exist in pairs that are structurally similar and proved that sperm and egg cells each have one pair of chromosomes. Sutton's work advanced genetics by identifying the relationship between Mendel's laws of heredity and the role of the chromosome in meiosis.

Along with Bateson, the American geneticist Thomas Hunt Morgan (1866–1945) is often referred to as the "father of classical genetics." (See Figure 1.5.) In 1907 Morgan performed laboratory research using the fruit fly Drosophila melanogaster. He chose to study fruit flies because they bred quickly, had distinctive characteristics, and had just four chromosomes. The aim of his research was to replicate the genetic variation de Vries had reported from his experiments with plants and animals.

Working in a laboratory they called the "fly room," Morgan and his students Calvin Bridges (1889–1938), Hermann Muller (1890–1967), and Alfred Sturtevant (1891–1970) conducted research that unequivocally confirmed the findings and conclusions of Mendel, Bateson, and Sutton. Breeding both white- and red-eyed fruit flies, they demonstrated that all the offspring were red-eyed, indicating that the white-eye gene was recessive and the red-eye gene was dominant. The offspring carried the white-eye gene but it did not appear in the first generation. When, however, the F1 offspring were crossbred, the ratio of red-eyed to white-eyed flies was 3:1 in the FIGURE 1.5
Thomas Hunt Morgan.The Library of Congress. next generation (F2). (A similar pattern is shown for red and white flowers in Figure 1.3.)

The investigators also observed that all the white-eyed flies were male, prompting them to investigate sex chromosomes and hypothesize about sex-linked inheritance. The synthesis of their research with earlier work produced the chromosomal theory of inheritance, the premise that genes are the fundamental units of heredity and are found in the chromosomes. It also confirmed that specific genes are found on specific chromosomes, that traits found on the same chromosome are not always inherited together, and that genes are actual physical objects. In 1915 the four researchers published The Mechanism of Mendelian Heredity (New York: Holt), which detailed the results of their research, conclusions, and directions for future research.

In The Theory of the Gene (New Haven, CT: Yale University Press, 1926), Morgan asserted that the ability to quantify or number genes enables researchers to predict accurately the distribution of specific traits and characteristics. He contended that the mathematical principles governing genetics qualify it as science:

The characters of the individual are referable to paired elements (genes) in the germinal matter that are held together in a definite number of linkage groups. …The members of each pair of genes separate when germ cells mature.… Each germ-cell comes to contain only one set.… These principles … enable us to handle problems of genetics in a strictly numerical basis, and allow us to predict … what will occur.… In these respects the theory [of the gene] fulfills the requirements of a scientific theory in the fullest sense.

In 1933 Morgan was awarded the Nobel Prize in physiology or medicine for his groundbreaking contributions to the understanding of inheritance. Muller also became a distinguished geneticist, and after pursuing research on flies to determine if he could induce genetic changes using radiation, he turned his attention to studies of twins to gain a better understanding of human genetics. In 1946 he was awarded a Nobel Prize for his research on mutations, the source of all genetic variation.

Bridges eventually discovered the first chromosomal deficiency as well as chromosomal duplication in fruit flies. Bridges served in various academic capacities at Columbia University, the Carnegie Institution, and the California Institute of Technology and was a member of the National Academy of Sciences and a fellow of the American Association for the Advancement of Science.

Sturtevant was awarded the National Medal of Science in 1968. His most notable contribution to genetics was the detailed outline and instruction he provided about gene mapping—the process of determining the linear sequence of genes in genetic material. In 1913 he began construction of a chromosome map of the fruit fly that was completed in 1951. Because of his work in gene mapping, he is often referred to as the "father of the Human Genome Project," the comprehensive map of humanity's more than 30,000 genes. His book, The History of Genetics (New York: Harper & Row, 1965), recounts the ideas, events, scientists, and philosophies that shaped the development of genetics.