Approaches to the In Vivo Finictioii of 

 Subcellular Particles ^ 



ALEX B. NOVIKOFF 



Albert Einstein College of Medicine 

 New York City 



THANKS TO BRACHET (3) wc havc available a popular term which includes the 

 subject matter of this conference, Biochemical Cytology — or, if biochemists 

 prefer. Cytologic Biochemistry. 



Perhaps it is a sign of maturity ot the held that one notes a growing tolerance 

 by specialists in one area of the vast domain of biochemical cytology for the 

 pursuits of those in other areas. There are fewer 'gloomy critics,' as I like to call 

 those people with essentially destructive comments on a technic]ue which they do 

 not themselves employ. 



We can all recall the categorical assertion that hope for significant information 

 concerning the in vivo function of subcellular particles was lost the moment the 

 cell was disrupted or homogenized. Or, that the use of aqueous media like sucrose 

 could yield only misleading particles, especially worthless nuclei. Or, that oxida- 

 tive phosphorylation could never be retained once the organized structure of the 

 complete mitochondrion was broken. Or, that electron microscopy was one huge 

 blunder, based as it was on osmium artifacts. Or, that quantitative microspectro- 

 photometry of stained tissue sections was deprived of meaning by the marked 

 structural heterogeneity of the subcellular particles. Or, that enzyme destruction 

 by fixative, and diffusion of reaction product during incubation, made staining 

 methods worthless for demonstrating the intracellular in situ localization of 

 enzymes, particularly important ones. 



It might be asserted by some that the 'gloomy critics' have helped focus on the 

 pitfalls of biochemical cytology techniques. Others may consider this debatable 

 and contend that it is data rather than critics which move investigators to refine 

 their methods. As the field of biochemical cytology has developed, not only have 

 technical refinements been introduced, but increasingly within the same, or nearby, 

 laboratories integrated studies are pursued, with two or more techniques applied 

 to the same problem. 



^ Work from our laboratory has been supported by grants from the American Cancer Society, 

 Inc.: Public Health Service, U.S. Dcpt. of Health, Education and Welfare; and the National 

 Science Foundation. 



