INTRODUCTION TO FIXATION 27 



make the structural resemblance between the final preparation and 

 the living tissue as close as possible. 



The appearance given in a fixed microscopical preparation is 

 nearly always to some extent artificial. The artifacts (p. 329) are of 

 two main kinds: intrinsic, or caused by distortion of the original 

 tissue-constituents; and extrinsic, or caused by the deposition 

 within the tissue of extraneous objects (such as the mercury pre- 

 cipitate mentioned on p. 103). Intrinsic artifacts are of two kinds: 

 primary, or produced by the fixative itself and therefore visible 

 while the tissue still lies in the fixative ; and secondary, or produced 

 by subsequent treatment. 



Intrinsic artifacts are much more frequent than extrinsic. On 

 the w^hole they have a more serious effect on cells than on inter- 

 cellular matter, though connective tissue fibres are often wrinkled 

 and intercellular spaces distorted. Cells are subject to several 

 different kinds of artificial changes.*^* Objects that are present in 

 the living cell may simply disappear. Lipid globules, for instance, 

 may be dissolved away. Protoplasm may be coagulated in the form 

 of networks or lumps. So frequent is the network appearance in 

 microscopical preparations that it was formerly supposed to be a 

 character of the living substance; but Hardy ^^^ showed in 1899 

 that fixatives produced just such a microscopical network when 

 they coagulated a solution of albumin, and that some fixatives 

 made a coarse and others a fine net. Another frequent artifact is the 

 thickening of membranes. Protein is often coagulated on the inner 

 side of the nuclear and cell-membranes. Retractions also occur. 

 The nuclear membrane is frequently pulled away from the sur- 

 rounding cytoplasm, and both this and the cell-membrane are 

 frequently wrinkled. Blebs of cytoplasm are often extruded from 

 the surfaces of cells directly exposed to the fixative. The technical 

 term for this process is clasmatosis, but it is often called bubbling. 

 The latter is a misleading term, for no gas is formed. 



Only by reference to the living cell can the quality of a fixative 

 be judged. This fact can scarcely be too strongly emphasized. If, 

 however, a particular fixative gives faithful stabilization of struc- 

 ture with certain chosen cells that have been carefully studied in 

 the living state, we have reason to trust it with others that cannot 

 be isolated for vital study. 



Fixation for electron microscopy presents us with special 

 problems. Electron micrographs that show objects of microscopic 



