Interferon and cell differentiation

Abstract

It is indeed a pleasure and a privilege to be asked to give this lecture in memory of a fine medical scientist, whose career was cut so sadly short by violence. In looking at the program today I cannot help but think of another scientist, to whom this field owes so much, whose life was also cut short unexpectedly. Alick Isaacs, the discoverer of interferon, was a brilliant medical scientist and it is a matter of regret to us all that he did not live to see the discovery which he had made, spread so pervasively through the modern medical sciences. I was fortunate enough to work with Alick Isaacs for five years at the National Institute for Medical Research and I was working with him when interferon was discovered. At that time, I was working on the nucleic acids of influenza virus, for it was not known whether they contained RNA, DNA or both; indeed it was still the days of ' after all, the basic phenomena which Alick had observed and which led to the discovery of interferon, had been seen by a number of other investigators who had failed to see the significance of the data -dismissing it as some spurious effect. As I said, we titrated interferon using influenza virus as a challenge and a haemaglutination assay to measure the virus yield. The red cells took about half an hour to settle -so that there was a period of waiting after the titration had been finished before we knew the results of the experiment. Alick always carried a little hand lens in his lab coat pocket and would use this to look at the perspex plate in order to be able to tell as soon as possible where the titration end point was going to be. Long before the cells had settled fully he had interpreted the experiment and planned two or three more. Just occasionally his lens led him astray and after the cells had settled he realised the answer was different, but he would rise to this task very quickly, always producing a stream of new ideas. I found this extremely stimulating, for I had trained in organic chemistry, then a more precise and logical science but with less scope for the imagination, and the way in which biology was then yielding to a molecular approach has, of course, fascinated my generation for the rest of our lives. Alick thought broadly, suggesting ideas which were sometimes wild but always testable. His vision of interferon was broad; for example, when he suggested that it could be regarded as a response to foreign nucleic acids, stimulated by the ideas of foreigness, which Burnet was talking about in immunology at that time. He also tried to relate the

Actions of recombinant human γ‐interferon and tumor necrosis factor α on the proliferation and osteoblastic characteristics of human trabecular bone cells in vitro

“…It is perhaps pertinent, however, that PGE production is probably augmented by increasing substrate availability by phospholipase A2 actions in the membrane (31), whereas actions on protein synthesis (such as alkaline phosphatase) and proliferation are probably exerted by interactions in the nucleus. It has also been reported that interferon has different actions according to cell type and the stage of the cell cycle (32). Using our culture system, which contains both mature osteoblasts and their precursors, interferon's actions on proliferation probably occur on the pre-osteobiasts, whereas it affects alkaline phosphatase production in the mature osteoblast.…”

Interferons as Hormones of Pregnancy*

“…For example, chicken embryo cells from later developmental stages produce more IFN in response to an inducer than cells from earlier stages (156). For example, chicken embryo cells from later developmental stages produce more IFN in response to an inducer than cells from earlier stages (156).…”

Modulation of placental alkaline phosphatase activity and cytokeratins in human HN-1 cells by butyrate, retinoic acid, catecholamines and histamine

“…Indirect labeling of keratins with a polyclonal antibody showed that cytokeratin content was enhanced by butyrate but not by retinoic acid. Further analysis of cytokeratin content using four monoclonal antibodies showed that labeling of cytokeratins (5+8) As is shown in numerous reports, butyrate, retinoic acid, interferon, glucocorticoids, polar solvents, and certain chemotherapeutic agents can modulate terminal differentiation (Augeron & Laboisse, 1984;Burke, 1986;Jetten, 1984;Reiss et al, 1985;Sartorelli, 1985), accompanied by inhibition of proliferation (Pierce & Wallace, 1971;Prasad & Sinha, 1976), morphological changes (Abe & Kufe, 1984;Kamech et al, 1986), and an increase in the production of specific antigens and enzymes (Reese & Politano, 1981;Morita et al, 1982;Abe & Kufe, 1984;Reese et al, 1985), such as CEA and alkaline phosphatase. These effects were in most cases reversible, although some authors claimed a more permanently affected cell progeny after treatment (Augeron & Laboisse, 1984;Reiss et al, 1985).…”