Phage Findings

Last week Bacteriologist Albert Paul Krueger of the University of California elaborated a recent announcement of a discovery concerning bacteriophage, the mysterious bacteria-destroying substance which has had a stormy medical history in the 22 years since it first came to light. Bacteriophage--"phage" for short--was discovered during the War by a British medical officer named Frederick William Twort, who was preparing vaccines. When he stained one of his germ colonies he found nothing but the wreckage of dead bacteria. Whatever it was that killed them was able to pass in solution through a fine filter and then infect other colonies. Felix d'Herelle, a Canadian studying at France's Pasteur Institute, found that another kind of phage was fatal to the dysentery bacillus, and that dysentery patients treated with it showed improvement.

D'Herelle prematurely decided that he had a cure for all bacterial diseases, and phage became a sensation. (The young doctor in Sinclair Lewis' Arrowsmith was a phage researcher.) More than 50 different phages were found, and some of them were photographed by ultraviolet light in ultra-microscopes, revealing diameters of two to 90-billionths of a metre. They were tried out as cures for cholera, dysentery, blood poisoning, boils and other diseases, but on the whole proved disappointing. Some bacteria seemed to acquire an immunity to their phages. Some phages worked well in test tubes, failed in human bodies. Thus phage does not cut a major figure in the therapy of bacterial diseases today.

But research on phage was by no means abandoned, and the possibility remained that it might be extremely useful if more were known about it. Was it alive or not alive? What did it consist of chemically? Did it always require the presence of a bacterial host to propagate itself--or could it, under favorable circumstances, multiply alone?

One of those who took the position that phage was not alive was Albert Paul Krueger, who began studying the mysterious killer as a medical student at Stanford. For two years he continued his research at the Rockefeller Institute, went on to the University of California. He discovered a phage of staphylococci (pus germs), showed that its inactivation by heat followed the same course as that of a protein. Poisons such as potassium cyanide and bichloride of mercury inactivated but did not kill it--in other words, like protein, it regained activity after the poison was removed. Finally Rockefeller Institute's John Howard Northrop isolated a phage, showed it to be a protein with the catalyzing properties of an enzyme. These researches convinced many a bacteriologist that phages are nonliving protein molecules, like Wendell Meredith Stanley's crystallized virus which causes tobacco mosaic disease in plants.

Until recently there was no evidence that phage could multiply except in the presence of active bacteria. Krueger, however, made it multiply in the presence of bacteria in the quiescent or nondividing state. It seemed that a phage precursor (parent substance) was secreted by the bacterial cells, that this was chemically activated by the phage to produce more phage. Last week Dr. Krueger announced that he had propagated phage without any bacteria at all. He drained off the precursor through a filter, added phage to it, found that more phage was evolved in unlimited quantities. This phenomenon has a close analog in the behavior of a well-known protein: trypsinogen, inactive precursor of the enzyme trypsin. When trypsinogen extracted from pancreas is added to trypsin, the trypsin begins to multiply. These findings may be of great help to researchers seeking a cure for such virus diseases as poliomyelitis and encephalitis.

Tall, tweedy Dr. Krueger, born 36 years ago in Montana, is a lieutenant commander in the Naval Reserve, a title conferred on him for suggesting and initiating a laboratory research unit for the Navy staffed by university scientists. Married and father of two, he likes fishing, archery. At present he is planning to find out what happens to phage when it is bombarded by powerful atomic projectiles in the cyclotron of University of California's Ernest Orlando Lawrence.

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