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The surprises of mammalian molecular cell biology

Nature Medicine volume 8, pages 1068–1071 (2002)Cite this article

The opportunity provided by the Albert Lasker Award for Special Achievement in Medical Science to reflect on my 'career' does not, I am sure, give me license to dwell on the humid, sweltering summers of a childhood in Mississippi. But perhaps I may be permitted to say a brief word of thanks to my teachers at the University of Mississippi, especially Dean Parker, a Drosophila geneticist of the T.S. Painter School, and Robert Glaser, at the time an assistant professor of medicine at Washington University School of Medicine. Parker taught us what a gene was and how to observe its effects, but it was in Robert Glaser's rheumatic fever laboratory that I tried to do my first experiments. A colleague, Stephen Morse, and I infected rabbits in their tonsils with Group A streptococci in an effort, not completely unsuccessful, to mimic the secondary heart muscle damage that occurs in rheumatic fever as a sequel to infection by Group A streptococci1.

With Leon Levintow (Fig. 1), a biochemist in the Eagle laboratory, my aims turned to charting the course of virus RNA and virus protein formation to compare this with infectious virus formation. Jerome Vinograd, the father of equilibrium density gradient centrifugation using cesium salts, visited Eagle's laboratory and told us about his work. We were soon able to purify poliovirus conveniently using the equilibrium density gradient technique. By labeling infected cultures with either amino acids or adenosine at various intervals after infection and then purifying the cultures and measuring the radioactivity in the virus at the conclusion of one virus cycle, we could chart how much virus protein or RNA had been made at the time the label was added. We could then deduce the 'growth curve' of the virus constituents to compare this with the growth curve of the infectious virus particles obtained from disrupted cell samples3,4. This was in 1959, before the idea of messenger RNA (mRNA) was born. I was intrigued with the finding that poliovirus RNA was made before poliovirus protein and wondered what it meant. I knew during this time I should eventually leave 'the Eagle's nest', and Bob DeMars suggested that my next step in scientific education plus cultural enlightenment (equally necessary) was to go to Paris and work with Francois Jacob and learn genetics. Eagle agreed that this was a splendid idea and offered to send me and provide me at least a semi-permanent position upon my return to Bethesda. Thus I applied to Andre Lwoff, Chef de Service de Physiologie Microbienne at the Pasteur Institute, in whose service Jacob worked. On one gloriously happy June day in 1959, I received a letter of acceptance from Lwoff.

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Figure 1
Figure 2: Sedimentation and base composition analysis of HeLa cell nuclear RNA and polysomal mRNA.
Figure 3: Analysis of 32P-labeled poly(A)-selected hnRNA and polysomal mRNA.

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Acknowledgements

I thank my more than 150 colleagues, only a few of whom were mentioned, that have journeyed with me on this voyage.

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  1. Laboratory of Molecular Cell Biology The Rockefeller University, New York, New York, USA

    James E. Darnell Jr.

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Darnell, J. The surprises of mammalian molecular cell biology. Nat Med 8, 1068–1071 (2002). https://doi.org/10.1038/nm773

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