Morgan, Thomas Hunt

Training and Early Interests

Morgan was born and raised in Kentucky, and received his bachelor's degree from the State College of Kentucky in 1886. He pursued graduate study at Johns Hopkins University in Baltimore, and eventually became a professor of biology at Bryn Mawr College in 1891. His early interests were in developmental biology and evolution. After moving to Columbia University in 1901 and coming under the influence of the great cell biologist Edwin Wilson, Morgan turned his attention to understanding the physical basis of inheritance, which he saw as a means to test theories about the role of mutation in evolution.

At the time Morgan began his work, chromosomes had been seen in cells, but their significance was unknown and not widely considered. A student of Wilson's, Walter Sutton, had recently proposed that chromosomes carried the genetic material, but had little evidence to support this important hypothesis. At the time, the gene itself was an abstract concept with no known physical correlate, and many scientists thought it was not a physical entity at all, but only a convenient fiction for describing some experimental results. In fact, it was Morgan's use of the term "gene" that helped bring it into general use in science.

To attack the issue of heredity, Morgan chose to work with the fruit fly, Drosophila melanogaster. This fly requires little space, breeds quickly, has many observable characteristics, and has only four chromosomes, making it an ideal model organism for genetics studies. Morgan also gathered a trio of very bright students, Hermann Muller, Alfred Sturtevant, and Calvin Bridges, and cultivated an egalitarian system of collaboration that was unknown in most other labs. The combination of the right question, the right model, the right collaborators, and some luck allowed Morgan and his group in their lab, dubbed "The Fly Room," to make their fundamental discoveries. Beginning in 1908, they proved that chromosomes do indeed carry the genes, that genes are discrete physical things arranged on chromosomes like beads on a string, that genes change places on chromosomes, that genes can be mutated and those mutations are faithfully inherited, and that mutations can be caused by exposure to high-energy radiation or other environmental phenomena.

A Lucky Discovery

This long string of seminal discoveries began with the discovery of a single male white-eyed fly among the many thousands of normal red-eyed ones. Morgan bred this mutant male with a red-eyed female. All the offspring were red-eyed, indicating the white form of the gene (called the white allele) was "recessive" to the dominant red allele: Flies carried the mutant allele, but its effects did not show up. When these offspring were crossed, the ratio of red to white was 3:1, just what would be expected for a classical recessive trait.

However, Morgan noted an unusual fact about the white-eyed flies—all of them were male. Morgan knew that the female Drosophila had two so-called X chromosomes, while the male had only one. Combining this fact with his discovery that only males showed the white-eye trait, he reasoned that the white-eye mutant allele must be on the X chromosome. Males show the white-eye trait because the mutant white allele is the only one they have—they don't have a second X chromosome with a normal red allele. Females rarely show the white-eye trait, because they have a normal redeye allele on the other X chromosome.

Morgan's results showed that the white-eye allele is inherited on the X chromosome, and confirmed the discovery that the X chromosome helps determine sex, first shown in 1905 by Sutton and Nettie Stevens. In one step, his discovery proved that genes, the factors governing inheritance, are carried on chromosomes, and that specific genes are carried on specific chromosomes. This provided the crucial evidence that genes are indeed discrete physical objects.

Linkage and Chromosome Mapping

The discovery of more mutated genes allowed Morgan's group to explore how genes are arranged on the chromosome, and to discover an exception to one of Mendel's laws of inheritance. Mendel had proposed the Law of Independent Assortment, stating that the alternative forms of different traits (such as round versus wrinkled pea seeds and short versus tall plant height) separate and recombine independently of each other, so that, for instance, obtaining a wrinkled tall plant is just as likely as obtaining a wrinkled short plant.

Morgan found this was not always true. Rather, certain combinations of alleles are very unlikely to be separated from each other, a fact he attributed to co-inheritance of the two alleles on the same chromosome. While alleles on separate chromosomes assort independently, as Mendel predicted, those on the same chromosome travel together unless separated.

To explore this, Morgan crossed a red-eyed fly with normal-length wings with a purple-eyed fly with stubby wings. After two generations, Mendel's laws predicted that all possible combinations of eye color and wing length should be equally likely. Instead, Morgan found that most flies had the original trait combinations, while red-eyed, stubby-winged flies were rare, as were purple-eyed, normal-winged flies. He concluded that the genes for wing length and purple eye color were on the same chromosome. Like passengers traveling on the same ship, once the particular alleles were together, they tended to stay linked. (Note that the purple eye-color gene is not the same one as the red-white eye-color gene he discovered previously, and is not on the X chromosome.)

However, Morgan noted specific allele combinations didn't always stay together: There were a few flies whose stubby-wing allele and purple-eye allele had become separated from each other. This led Morgan to propose that chromosomes sometimes exchange segments, allowing their passengers to change vessels, so to speak. This phenomenon is known as crossing over, and was later conclusively demonstrated in maize by Barbara McClintock.

Crossing over is now known to occur only during meiosis, the chromosome division that leads to formation of eggs and sperm. During meioisis, homologous chromosomes originally donated from the mother and father pair up for an extended period. In this period, called synapsis, the maternal and paternal chromosomes randomly exchange several segments, resulting in a pair of chromosomes with a mix of maternally derived and paternally derived alleles. These then separate to form the eggs and sperm.

Morgan's student Sturtevant reasoned that the likelihood of two alleles becoming separated during crossing over was proportional to the distance between them. In other words, the closer they are, the more likely they will stay together, and the further apart they are, the more likely they will separate. If A, B, and C are on the same chromosome, and A stays with B more often than it stays with C, then the distance from A to B is shorter than the distance from A to C. In this way, the relative distances of genes can be determined, providing a "linkage map" of the chromosomes. The unit of relative distance is called the morgan, in honor of Morgan himself. Calvin Bridges later devised a method to determine the absolute distance between genes, relying on the distinct banding patterns seen in Drosophila chromosomes in the larval stage.

Morgan's Legacy

In 1915 Morgan, Bridges, Sturtevant, and Muller published The Mechanism of Mendelian Heredity, a highly influential textbook laying out the evidence for the chromosomal theory of heredity and illustrating their methods so others could apply them in further research. In 1928 Morgan moved to the California Institute of Technology to found the Division of Biology. Sturtevant and Bridges went with him. Five years later Morgan was awarded the Nobel Prize in physiology or medicine for his work in genetics. He shared the prize money with Sturtevant and Bridges. Besides his own discoveries, Morgan's intellectual legacy includes the historically important researchers who trained with him, including Theodosius Dobzhansky, who applied the new genetics to an understanding of evolution. Another of his students was George Beadle, who discovered that mutations affect the working of proteins, and proposed the "one gene-one enzyme" definition of the gene.

SEE ALSO FRUIT FLY: DROSOPHILA ; LINKAGE AND RECOMBINATION; MCCLINTOCK, BARBARA; MEIOSIS; MENDEL, GREGOR; MULLER, HERMANN.

Richard Robinson

Bibliography

Allen, Garland E. Thomas Hunt Morgan: The Man and His Science. Princeton, NJ:Princeton University Press, 1978.

Judson, Horace F. The Eighth Day of Creation: The Makers of the Revolution in Biology.New York: Simon & Schuster, 1979.

Morgan, Thomas Hunt, et al. The Mechanism of Mendelian Heredity. New York: HoltRinehart & Winston, 1915. Reprint, with an introduction by Garland E. Allen, New York: Johnson Reprint Corporation, 1978.

Sturtevant, Alfred H. A History of Genetics. New York: Harper & Row, 1965.