Review from Spektrum der Wissenschaften

Healthy Through Viruses – a way out of the antibiotic-resistance crisis

After the political collapse of the Soviet Union, the number of cases of consumption doubled there within only seven years. Today one of 300 inhabitants in the area of the Aral Sea is sick with tuberculosis – a dramatically high number. Between 1972 and 1992 in New York, a disease epidemic due to multi-drug-resistant mycobacteria was rampant, with approximately 400 new TB infections per year, and it cost an estimated billion dollars to control this outbreak. Nosocomial infections – hospital acquired infections – and multi-resistant pathogens, terms which until recently were familiar only to experts, are today topics of the public press. And it is not surprising because, in Germany alone, 20,000 people die annually of nosocomial infections.

The prospects for the future are even gloomier. While it took approximately fifty years before 95 per cent of Staphylococcus aureus strains became resistant to penicillin, today so-called problem bacteria need only a few years to acquire resistance to a totally new class of antibiotics. Additionally, the pharmaceutical industry has far less promising chemical antimicrobials in the research pipeline than they had a decade ago. At the same time, the need continues to increase: ever more patients must be protected against the threat of infections because of weakened immune systems or because they are organ transplant recipients.

New hope is promised by a therapy which is substantially older than penicillin: treatment with bacteriophages. On August 2, 1919, their discoverer, the French Canadian Felix d’Herelle, administered a cloudy broth containing Shigella phages to a deathly-ill boy at the Pasteur Institute in Paris, curing him of dysentery. After an early, world-wide boom, this therapy today is little used outside the former Soviet republic of Georgia and is only now again receiving attention in the West, with many infection control specialists remaining skeptical.

This paradigm shift is the background for an unusually well researched, outstandingly well written and scientifically grounded book by the Swiss journalist Thomas Häusler. From the beginnings to the present, the author, who also holds a doctorate in biochemistry, describes all aspects of a concept (bacteriophage therapy) whose therapeutic potential is not easily communicated during times of AIDS and SARS.

Bacteriophages are indeed extremely dangerous viruses, but with the important difference that they are specialized in attacking only bacterial cells and they do no harm to animal cells. When a phage discovers a bacterium to which it possesses the correct key – that is to say that on the bacterial cell surface there are suitable receptors to which the phage can attach with its tentacle-like extensions – then the phage will inject its hereditary DNA into the bacterial cell within minutes. Taking over the bacterial cell’s biochemical apparatus, hundreds of phage copies are then produced. Special proteins (holins and lysins) break the cell wall open from the inside, the bacterial victim dies, and the released daughter phages attack any remaining sensitive bacterial cells like a pack of hungry wolves.

The advantages of the therapy are obvious. Bacteriophages are very specific parasites and, contrary to antibiotics, do not damage the useful bacteria which live in and on the body. Due to their mode of action, they induce less resistance problems, and if a pathogen is insensitive, then it is most likely that there exists another virus (phage) which will act as the bacteria killer. Phages are ’intelligent’ medicines: They increase just where they are needed (while antibiotics often do not even get to where they are to work).

The high specificity with which phages look for their bacterial victims is at the same time also their therapeutic Achilles‘ heel. Either the infection control specialist must have a cocktail containing many different types of phages, or a phage specifically effective against the pathogen of each patient must be identified through detailed microbiological analytical work and must then be mass-produced. In both cases regulatory authorities tend to loath recognizing such manually produced anti-infection agents as medicines.

For chronic infections on external and internal body surfaces due to multi-resistant pathogens which can not be treated with current methods, phage therapy could become a kind of miracle medicine. Additionally, phages could bring an end to feeding antibiotics in large-scale animal production.

Throughout the book, interviews with researchers who are active at the front of new developments are skillfully intertwined with descriptions of actual patient outcomes. The middle part of the book is also outstanding in describing the trials and errors of phage therapy as practiced between 1930 and 1990. Here, journalist Häusler points out what influence political events have on medical research – from the ’Great Patriotic War’ of Russia against Nazi Germany to the collapse of the Soviet Union and up to September 11, 2001. A long list of footnotes, a detailed list of references and numerous instructive illustrations supplement the text excellently.

A book dealing with an explosive topic, such as one cannot make better.

(Original in German in Spektrum der Wissenschaft, Feb. 2004, p. 95. By Hermann Feldmeier, Professor of Tropical Medicine at the Free University, Berlin and Physician for Microbiology and the Epidemiology of Infectious Disease. Translated by G. W. Riedel and E. Kutter.)