ExperimentalGerontology, Vol. 27, pp. 363-368, 1992 0531-5565/92 $5.00 + .00 Printed in the USA. All rights reserved. Copyright© 1992 Pergamon Press Ltd. AGING, LONGEVITY, AND IMMORTALITY IN VITRO LEONARD HAYFLICK Universityof California, San Francisco,Schoolof Medicineand VAMC,Cell Biology and AgingSection ( 151 E), 4150Clement Street, San Francisco,California94121 Key Words: aging, longevity, immortality, cell aging, cell lines, cell strains, Phase !II THIRTY YEARSago, when I first realized that our work might be telling us something about aging, only a few dozen intrepid people did research in gerontology. At that time the stigma of conducting research in a field recognized for centuries as a black art commanded little scientific respect. And, those using cell cultures in gerontological research 30 years ago were doubly damned because cell culture itself was just emerging from condemnation as a black art. In the late 1950s the main dogma in cell culture was that all cultured cells have the potential to replicate indefinitely in culture, and if they fail to do so, it is simply a reflection of our ignorance of how best to cultivate them. Thus it was no surprise when we found that the fibroblast cell cultures we grew from human fetuses luxuriated for some months and then died. It was no surprise because, with one notable exception and ever since the development of cell culture techniques in the early 1900s by Ross Harrison, every single culture of normal cells ever set ultimately died. It was not until Wilton Earle produced the L cell line in the early 1940s that the first alleged immortal cell line was discovered. I say "alleged" because I do not believe that there are immortal cell cultures--a speculation I will return to later. The paper that Paul Moorhead and I published in 1961 (Hayflick and Moorhead, 196 l) really did not report anything profoundly new when we suggested that cultured cells have a finite capacity to replicate. What was novel in our report was that, unlike our predeces- sors, we proved the cells to be normal, demonstrated that their loss of replicative capacity was not an artifact, and interpreted the phenomenon as aging at the cell level. Before Moorhead's work, no one had shown that cells serially cultured from normal tissue were karyotypically normal. One of the many reasons why this was important was that the dogma stating that all serially cultured cells were potentially immortal had a corollary: Serially passaged cells always transform to become cancer cells and are karyotypically abnormal. Evidence for the alleged truth of this corollary was to be found in the L cell line and in the HeLa and other human cell lines that by 1961 were being reported by dozens of cell culturists. Correspondenceto: L. Hayflick, 36991 GreencroftClose,P.O. Box 89, The Sea Ranch, CA 95497. 363