William S. Tillett
New York University
New York University
For the discovery and purification of the enzymes, streptokinase and streptodornase.
In the course of certain diseases or following injury, an accumulation of pus or fibrin clots frequently occurs which may seriously delay or prevent healing. Up to the present, the treatment of such conditions has been by surgical evacuation, which often included major plastic operations for repair. Through the distinguished collaborative investigations of Dr. William Tillett and Dr. L.R. Christensen at New York University College of Medicine, “streptococcal enzymatic debridement” has been discovered and developed as a new therapeutic principle of important clinical significance. In addition, our knowledge of the nature of a protein-digesting enzyme of human blood has been placed on a new basis and information gained on the composition of pus which changes previous concepts.
Dr. Tillett, an original and profound student of both the clinical and laboratory aspects of infectious disease, discovered in 1933 that hemolytic streptococci produce an enzyme, fibrinolysin, now known as streptokinase, a substance which dissolves human fibrin clots. Twelve years later, Dr. Christensen, a microbiologist with a strong biochemical bent, demonstrated, after a characteristically penetrating and persistent investigation, that streptokinase functions by activation of another protein-digesting enzyme present in blood plasma, but usually in an inactive state. He also described a method of purifying streptokinase which permitted its successful use in patients.
In the course of clinical studies on the liquefaction of fibrinous and purulent exudates, it was recognized for the first time that the viscous character of pus is due in great part to desoxyribose nucleoprotein; moreover, it was found that the streptokinase preparations contained an enzyme, streptococcal desoxyribonuclease (streptodornase) which, through its digestive action on nucleoprotein, causes thick pus to become thin and watery and thereby facilitates its removal. Methods for purifying this enzyme have also been developed by these investigators.
This demonstration of the mode of action and clinical effectiveness of streptokinase and streptodornase is a brilliant contribution to the treatment of human diseases in which accumulated fibrin or pus impedes healing or delays it indefinitely. It is not an exaggeration to state that the principles involved in the clinical use of these streptococcal products stand out as a therapeutic landmark.