In 1961, Leonard Hayflick and his colleague cytogeneticist Paul Moorhead conducted a series of definitive experiments in which they were able to demonstrate that normal human somatic cells have a finite number of replicative cycles. Today this phenomenon is known as the Hayflick Limit. In order to rule out any technical errors due to methodology or contamination, the two scientists mixed equal numbers of male cells, that had replicated many times, with female cells that had only replicated a few times. Unmixed cell cultures were used as controls. Once the male control cells stopped replicating they examined the mixed population of cells and found only female cells left. The results of this experiment disputed accepted dogma of the time that all normal vertebrate cells grown in culture were immortal and to this day there are still some skeptical scientists. In fact, the paper that resulted from their work was first rejected by the Journal of Experimental Medicine but finally was published in 1961 by Experimental Cell Research. To understand how pivotal their work has been, this paper has been cited over 3,000 times since it was first published. Hayflick interpreted his findings to mean that the limited replicative (in vitro) capacity of cultured normal cells was a manifestation of their aging and longevity. He also concluded that immortal cultured cells are predominantly cancer cells.
Once the concept of cellular aging was introduced, Hayflick concluded that an intracellular counting mechanism must exist, and Hayflick set out to find it. Scientists working in his lab discovered that the mechanism was located in the nucleus. The molecular explanation was revealed when it was noted telomeres located at the ends of linear chromosomes and first described in 1938 were involved. Telomere function was unknown, although it was suspected that they might have a role as a stabilizing structure. In many animals, including mammals, telomeres consist of thousands of hexameric repeats of the nucleotides TTAGGG. Knowing this sequence, scientists were then able to determine that telomeres became shorter each time a normal cell divided until a critical length was reached. at which time the cell stopped dividing. This is true in normal cells but not in cells that have undergone neoplastic (cancerous) transformation.
Transformation is a process in which normal cells convert to cells having the characteristics of cancer cells. One of the control points in the cell cycle involves the p53 tumor suppressor protein. This gene product inhibits tumor formation through induction of cell cycle arrest and/or apoptosis. In a recent Swedish study it was demonstrated that is also a powerful inhibitor of human telomerase reverse transcriptase (hTERT). Telomerase is a specialized RNA-directed DNApolymerase that extends telomeres of eukaryotic chromosomes especially in transformed cells. Telomerase gene expression is also active in germline cells (ova and sperm) and stem cells, and it is repressed in normal somatic cells. Repression of this enzyme entails the shortening of telomeres in each round of chromosomal replication. The elimination or reduction of telomerase activity has important implications in potential cancer therapies.
Besides his work on aging and cancer, Hayflick developed the first widely normal human diploid cell strain called WI-38 which is not only used in aging and cancer studies but was demonstrated to be superior to other cell substrates for the preparation of human virus vaccines. Today most of the worlds virus vaccines are made on Hayflick's cell strains. Hayflick also discovered the cause of "walking pneumonia" in humans, naming it Mycoplasma pneumoniae. Mycoplasma are the smallest free-living microorganisms. Besides the over 225 scientific papers and numerous book chapters he has written, Hayflick has also authored the popular book How and Why We Age first published by Ballantine Books in August 1994.
Born in Philadelphia, Pennsylvania, Dr. Hayflick obtained a Ph.D. in Medical Microbiology in 1956 from the University of Pennsylvania. His curriculum vitae includes numerous awards to mention and he has held throughout his career, varied faculty and government positions. In 1988, he joined the faculty at the University of California, San Francisco where he is a full professor of anatomy at the School of Medicine. Hayflick is also a member of several advisory boards and acts as an industry and government consultant. Hayflickis married and has five children.
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