The History of Genetics - Classical Genetics

Another American geneticist awarded a Nobel Prize was Barbara McClintock (1902–92), who described key methods of exchange of genetic information. Performing chromosomal studies of maize in the botany department at Cornell University, she observed colored kernels on an ear of corn that should have been clear. McClintock hypothesized that the genetic information that normally would have been conveyed to repress color had somehow been lost. She explained this loss by seeking and ultimately producing cytological proof of "jumping genes," which could be released from their original position and inserted, or transposed, into a new position. This genetic phenomenon of chromosomes exchanging pieces became known as crossing over, or recombination.

Together with another pioneering female researcher, Harriet Creighton (1909–2004), McClintock published a series of research studies, including a 1931 paper that offered tangible evidence that genetic information crossed over during the early stages of meiosis (cell division). Along with the 1983 Nobel Prize, McClintock received the prestigious Lasker Award in 1981, making her the most celebrated female geneticist in history.

During the same years, English medical microbiologist Frederick Griffith (1879–1941) performed experiments with Streptococcus pneumoniae, demonstrating that the ability to cause deadly pneumonia in mice could be transferred from one strain of bacteria to another. Griffith observed that the hereditary ability of bacteria to cause pneumonia could be altered by a "transforming factor." Although he mistakenly believed the transforming factor was a protein, Griffith's observation offered the first tangible evidence linking deoxyribonucleic acid (DNA, the molecule that carries the genetic code) to heredity in cells. His experiment provided a framework for researching the biochemical basis of heredity in bacteria. In 1944 Canadian-American immunologist Oswald Avery (1877–1955), along with Canadian-American microbiologist Colin Macleod (1909–72) and American bacteriologist Maclyn McCarty (1911–2005), performed studies demonstrating that Griffith's transforming factor was DNA rather than simply a protein. Among the experiments Avery and his colleagues performed was one similar to Griffith's, which confirmed that DNA from one strain of bacteria could transform a harmless strain of bacteria into a deadly strain. (See Figure 1.6.) Their findings gave credence to the premise that DNA was the molecular basis for genetic information.

Nearly half of the twentieth century was devoted to classical genetics research and the development of increasingly detailed and accurate descriptions of genes and their transmission. In 1929 the Russian-American organic chemist Phoebus Levene (1869–1940) isolated and discovered the structure of the individual units of DNA. Called nucleotides, the molecular building blocks of DNA are composed of deoxyribose (a sugar molecule), a phosphate molecule, and four types of nucleic acid "bases." (See Figure 1.7.) Also in 1929 Theophilus Painter (1889–1969), a cytologist, made the first estimate of the number of human chromosomes. His count of forty-eight was only off by two—twenty-five years later, investigators were able to stain and view human chromosomes microscopically to determine that they number forty-six. Analysis of chromosome number and structure would become pivotal to medical diagnosis of diseases FIGURE 1.6
Oswald Avery's experiments with DNA and Pneumococcus bacteria
SOURCE: "Oswald Avery's experiments showed that DNA from dead S strain of Pneumococcus bacteria could transform a harmless strain into a deadly strain," in Genetics, vol. 1, A–D, Macmillan Reference USA, Gale Group, 2002 and disorders associated with altered chromosomal numbers or structure.

Another milestone in the first half of the twentieth century was the determination by American chemist Linus Pauling (1901–94) that sickle-cell anemia (the presence of oxygen-deficient, abnormal red blood cells that cause affected individuals to suffer from pain and leg ulcers) was caused by a single amino acid (a building block of protein) substitute in the molecular structure of a protein, hemoglobin (the oxygen-bearing, iron-containing protein in red blood cells). Pauling's work paved the way for research showing that genetic information is used by cells to direct the synthesis of protein, and mutation (a change in genetic information) can directly cause a change in a protein. This explains hereditary genetic disorders such as sickle-cell anemia.

From 1950 to 1952 American geneticists Martha Cowles Chase (1930–2003) and Alfred Hershey (1908–97) conducted experiments that provided definitive proof that DNA was genetic material. In research that would be widely recounted as the "Waring Blender Experiments," the investigators dislodged virus particles that infect bacteria by spinning them in a blender and found that the viral DNA, and not the viral protein, that remains inside the bacteria directed the growth and multiplication of new viruses.

FIGURE 1.7
Deoxyribonucleic acid (DNA)
SOURCE: "Deoxyribonucleic Acid (DNA)," in Talking Glossary of Genetic Terms, U.S. Department of Health and Human Services, National Institutes of Health, National Human Genome Research Institute, http://www.genome.gov/Pages/Hyperion//DIR/VIP/Glossary/Illustration/nucleotide.shtml (accessed February 1, 2005)