David Hungerford
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David A. Hungerford, PhD, was a cancer researcher and co-discoverer of the Philadelphia Chromosome[1]. This discovery was the first association between a genetic abnormality and a type of cancer[2], and it changed the direction of cancer research and paved the way for the development of targeted cancer therapies.
Biography
David A. Hungerford was born in Brockton, Massachusetts in 1927. He received his bachelor’s degree from Temple University, and earned a PhD in zoology from the University of Pennsylvania.
In 1959, while working as a junior research fellow at the Institute for Cancer Research in Philadelphia (the precursor to Fox Chase Cancer Center), Hungerford and Peter C. Nowell, a pathologist at the University of Pennsylvania School of Medicine, discovered what became known as the Philadelphia Chromosome.
After earning his PhD in 1961, he spent more than two decades as a researcher at Fox Chase, retiring in 1982 due to health issues.
Hungerford died from lung cancer in 1993. His widow, Alice Hungerford, was also a longtime Fox Chase Cancer Center employee. She maintains his legacy and the family’s connection with Fox Chase via the David A. Hungerford Endowed Fund in Basic Chromosome Research. Every September she hosts an event to raise money for the endowment.
The microscope Hungerford was using when he made his discovery is on permanent public display at Fox Chase.
Discovery of the Philadelphia Chromosome
At the time of discovery Hungerford was pursuing his PhD, and was studying leukemia cells for a dissertation on human chromosomes. He detected a tiny abnormality in the chromosomes from cultured blood cells taken from two patients with chronic myelogenous leukemia (CML). Part of chromosome 22, and thus some of the genetic code it carried, appeared to be missing. Hungerford later discovered that it was not deleted or truncated, but translocated, meaning the missing piece was attached in a different spot on the chromosome. This abnormality would turn out to be the first consistent genetic irregularity associated with cancer in humans.
The discovery was called the Philadelphia chromosome after the city in which the researchers' respective institutions were located. They presented their findings in the Journal of National Cancer Institute in 1960. At the time, techniques for preparing chromosomes for microscopic study were still crude, and researchers had found no abnormal chromosomes in cells from patients with CML. Further studies verified the findings.
Other Scientific Contributions
Prior to the introduction of banding techniques on somatic metaphase chromosomes, David began investigating chromosomes at the pachytene stage in the development of sperm. Each chromosome has a specific, innate banding pattern (later shown to correlate to the banding pattern of somatic metaphase chromosomes), and in 1970 he described how the trisomy mutation associated with Down syndrome developed in meiosis. At the time of his retirement due to illness in 1982, David had mapped almost half of the normal human complement of chromosomes at pachytene[3].
Legacy
Hungerford’s and Nowell’s discovery provided the first evidence that cancer starts with changes in one or more genes. It galvanized the field of molecular biology—the study of such vital molecules as DNA, RNA, and the proteins that do each cell’s work.
The Philadelphia Chromosome became an important tool for diagnosing CML and monitoring treatment. More importantly, the idea it introduced linking culprit genes with cancers led to the creation of targeted drugs that block the effects of cancer-causing mutations. Drugs developed using the approach they made possible include Herceptin and Gleevec. Herceptin targets the gene involved in an aggressive form of breast cancer, and Gleevec blocks the effects of the cancer-causing gene on the Philadelphia chromosome and has proved effective in treating CML, as well as a rare sarcoma called gastrointestinal stromal tumor, or GIST.
Further reading
- https://www.foxchase.org/blog/2009-05-philadelphia-chromosome
- http://www.nytimes.com/1993/11/05/obituaries/david-a-hungerford-dies-at-66-found-genetic-change-in-cancer.html
References
- ^ Nowell, Peter C. (2007-08-01). "Discovery of the Philadelphia chromosome: a personal perspective". Journal of Clinical Investigation. 117 (8): 2033–2035. doi:10.1172/JCI31771. ISSN 0021-9738. PMC 1934591. PMID 17671636.
{{cite journal}}: CS1 maint: PMC format (link) - ^ "Chromosome Abnormalities and Cancer Cytogenetics | Learn Science at Scitable". www.nature.com. Retrieved 2018-04-24.
- ^ Hungerford, David A.; Mellman, William J.; Balaban, Gloria B.; LaBadie, Gundula U.; Messatzzia, Linda R.; Haller, Gail (September 1970). "Chromosome Structure and Function in Man, III. Pachytene Analysis and Identification of the Supernumerary Chromosome in a Case of Down's Syndrome (Mongolism)". Proceedings of the National Academy of Sciences of the United States of America. 67 (1): 221–224. ISSN 0027-8424. PMID 4248157.
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