Baltimore, MD—The Lasker Foundation awarded Carnegie’s Joseph G. Gall the prestigious 2006 Lasker Award for Special Achievement in Medical Science. The citation recognizes that Gall is “a founder of modern cell biology who has made seminal contributions to the field of chromosome structure and function, who invented in situ hybridization, and who has been a long-standing champion of women in science.”
Gall has been staff scientist at the Carnegie Institution’s Department of Embryology and adjunct professor of The Johns Hopkins University since 1983, and a Professor of Developmental Genetics of the American Cancer Society since 1984. His in situ hybridization technique, developed with graduate students Mary Lou Pardue and Susan Gerbi in 1969, is a powerful method that allows researchers to locate and map genes and specific sequences of DNA on a chromosome. It revolutionized molecular biology and is now used worldwide in gene studies.
“Joe Gall’s achievements are a realization of Andrew Carnegie’s original dream,” remarked Carnegie president Richard Meserve. “Carnegie believed that if exceptional individuals are set free to work in an environment without constraints extraordinary discoveries will result.”
Education and Career Path
As a teenager, Gall spent summers on a farm in northern Virginia, where his interest in the natural world flourished. “After much urging, my parents bought me a microscope when I was 14 years old—not one of the toys I had struggled with up to that time, but the real thing,” he reflected. Without a local high school to attend, Gall was sent to a boarding school near Charlottesville, Virginia, where after three years the headmaster thought he was ready to go to college. “How Yale was chosen I am not sure, but I arrived in New Haven in June 1945, just as the Second World War was coming to a close.”
Gall’s career-long interest is how the structure of the cell, particularly the nucleus, is related to the synthesis and processing of ribonucleic acid, RNA, during gene activity. He specifically looks at changes in the chromosomes and other nuclear components when RNA is synthesized, processed, and transported from the cell’s nucleus to the cytoplasm. The in situ hybridization technique takes advantage of the feature that DNA and RNA bond to each other via their complementary sequences. Gall and colleagues developed their technique of labeling RNA with a radioactive label and placing it on cells on a microscope slide. The RNA hybridizes, or binds, with its complement on the DNA and is detected by its radioactivity. This technique allows researchers to see where genes are and determine whether a gene has been turned on in developing embryos. The advent of fluorescent tags have increased the sensitivity and precision.
Gall’s development of in situ hybridization was a byproduct of his renowned research on the so-called lampbrush chromosomes—the largest chromosomes in any animal. They reside in amphibian eggs and were named when first viewed in the nineteenth century because they look like brushes then used to clean the narrow chimneys of lamps. Gall looks at the unlaid eggs from the frog Xenopus, which are up to 1.5 millimeters (mm) in diameter, with a nucleus, or germinal vesicle (GV), that is 0.4 mm in diameter. Their large size makes them ideal for understanding chromosome structure and function, Gall’s research area since the 1940s. Gall made many discoveries about genes in the lampbrush chromosome including gene amplification in which extra copies of DNA are created at certain times in the oocyte. Similar extra copies of genes are often seen in cancer cells.
Gall has worked with various organisms over the years, from frogs to the fruit fly. It has generally been thought that various factors involved in RNA synthesis travel separately to active genes on the chromosomes for processing. Using Xenopus eggs, Gall now studies this process. By watching fluorescently tagged molecules, he is able to determine where these factors move. This tracking has led Gall and others to propose that the processing machinery is assembled in structures in the GV, called Cajal bodies, named for the man who described them 100 years ago, Spanish neurobiologist and Nobel laureate Ramón y Cajal.
Allan Spradling, department director of Carnegie’s Department of Embryology, commented on Gall’s influence: “Joe Gall stands out especially because of the way he has done cutting-edge science throughout a long career. A true scholar of biology, he repeatedly turns his deep knowledge of diverse biological systems and of the forgotten lore of science history into novel experimental approaches that have sometimes spawned whole new fields of study. He shares his unmatched knowledge of microscopy in a unique course combining mathematically rigorous optics with a hands-on examination of historic instruments from every major phase of the field's development. All of these activities are carried out with the highest standards of integrity, respect for others, genuine modesty and with a sheer joy at the pleasures of discovery that seems undiminished from the days when he roamed the Virginia fields with his butterfly net and microscope. In short, Joe Gall's approach to science has long been an inspiration to others and I feel fortunate to count myself among those who have benefited enormously from his example.”
Honors and Awards
The Lasker Awards, considered the U.S. Nobels, recognize basic researchers and clinical scientists whose work has been seminal to understanding and treating disease. Since 1962, 71 Lasker Award recipients have gone on to win a Nobel Prize. The Special Achievement Award was created in 1994.
Carnegie geneticists Barbara McClintock and Alfred Hershey, both Nobel laureates, also won Lasker awards for their seminal research.
Andrew Carnegie founded the Carnegie Institution (http://www.carnegieinstitution.org/) in 1902 as an organization for scientific discovery. The Department of Embryology, founded in 1913 in affiliation with the Anatomy Department of Johns Hopkins University, is one of six departments within the institution. Carnegie scientists are leaders in plant biology, developmental biology, astronomy, materials science, global ecology, and Earth and planetary science.