The Cancer Journal - Volume 6, Number 2 (March-April 1993)
Drug-resistant microbes pose a new threat to our society. Infectious diseases
that were prevalent in the Thirties, e.g., pneumonia, meningitis, and typhoid,
and virtually disappeared after the discovery of antibiotics, are gradually
returning. More and more microbes become resistant to antibiotics. While in
1942 virtually all strains of Staphylococcus aureus worldwide were susceptible
to penicillin G, today more than 95% of Staphylococcus aureus worldwide are
resistant to penicillin, ampicillin, and anti-pseudomonas penicillins (1). Multi-drug
resistance is most pronounced in the recently emerging tubercle bacillus (2).
This alarming development was recently reviewed in "Science" (1-5).
Resistance may be acquired in several ways, e.g., chromosomal mutation, inductive
expression of a latent chromosomal gene, exchange of genetic material through
transformation, and conjugation with plasmid transfer of DNA (1). As the pharmaceutical
industry continues developing new antibiotics, more and more microbes become
resistant to a variety of drugs (4). After analyzing the biochemical and epidemiological
aspects of the problem, experts turn to the medical community with the following
advice: physicians should prescribe antimicrobials more selectively, should
be taught to prescribe the right antibiotics for a disease, and finish treatment
only when microbes were wiped out. Some companies advise "combination therapy",
using more than one drug, which may breed more drug-resistant microbes (5).
All this may be of no avail since massive doses of antimicrobials are given
to livestock.
"Bacteria are cleverer than men!" exclaims one expert (1), highlighting the
conceptual bankruptcy of modern microbiology. Nothing in their advice can avert
the danger. At best they hope to postpone it. Experts agree that "the solution
requires more than scientific breakthroughs" (3), but have little to suggest.
They hope to solve the issue by technology, disregarding its biological implications.
Microbes may be smarter than microbiologists but have never outsmarted the human
organism which learned how to resist them long before microbiology was conceived.
True, before the antibiotic era many had died from infectious diseases. On the
other hand, many more had survived them.
An infectious disease results from an interaction between microbes and host
defense e.g., inflammation or immunity (6). Defense strategies evolved throughout
the ages and from generation to generation became more efficient. According
to Darwin's theory, today's organisms are equipped with the best strategies
to deal with microbes, otherwise they would not have survived. The organism
and microbes maintain a delicate balance that is disturbed during infection.
Most antibiotics restore the balance by assisting strategies of the organism,
and when these fail, e.g., during agranulocytosis or agamma-globulinemia, antibiotics
are of no avail. This important aspect of health was forgotten in the wake of
the antibiotic era and is regarded as insignificant. A negligence that bred
multi-drug resistant microorganisms.
Darwin's law applies also to microbes that continuously improve their defense
strategies for dealing with antimicrobial agents. The heavier the selection
pressure, the more resistant they get Microbial resistance is an ecological
problem that may be averted only by reducing the use of antibiotics. Antibiotics
should be reserved only for humans and their administration to livestock, prohibited
or at least restricted drastically.
Contrary to the claim of microbiology, bacteria were not created in order to
destroy us. Of the 200,000 species of microbes on Earth only 400 are pathogenic.
Bacteria are deeply intertwined in the global food chain and it appears that
without their active participation in it, life on Earth would not be possible
(7). The indiscriminate administration of anhbiotics may threaten also this
important task, in the same way as toxic waste does to our environment. In view
of their importance to life, we should not wage a war against microorganisms,
as the expert suggests (3), but attempt to co-exist with them without endangering
our health.
A normal human being hosts about 1.2 kilograms of bacteria (8). The bulk are
in the gut lumen, and the rest in the skin, oro-pharynx, and genitalia. Some
are potential killers and yet they thrive without harming us. How do we protect
ourselves against our own flora and how could medicine apply this protection
against more dangerous pathogens? What is the secret of human carriers of pathogens
who remain unharmed? Our flora might even protect us against dangerous microbes,
e.g., hospital strains, by preventing their colonization in our body. After
all, in order to infect us an antibiotic-resistant microbe has to enter a niche
in our body that might be already occupied by our own "protective" flora. Such
ideas should be explored and considered during antibiotic treatment.
The phenomenon of anti-microbial resistance to chemotherapy is also relevant
to cancer chemotherapy. It is assumed that cancer cells will ultimately respond
to chemotherapy in the same way as microbes do. Unfortunately each treatment
breeds resistant cancer cells, exactly as in bacteria. Oncology should therefore
turn its attention to the role of the organism in cancer and stop its indiscriminate
prescription of chemical drugs.o
G. Zajicek
REFERENCES
1. Neu HC. The crisis in antibiotic resistance. Science 257, 1064-1072, 1992.
2. Bloom BR, Murray CJL. Tuberculosis: Commentary on a re-emerging killer. Science
257, 1056-1063,1992.
3. Koshland Jr. DE. The microbial wars. Science 257, 1021,1992.
4. Cohen ML. Epidemiology of drug resistance: implications for a post-antimicrobial
era. Science 257, 1050-1055,1992.
5. Gibbons A. Exploring new strategies to fight drug-resistant microbes. Science
257, 1036-1038,1992.
6. Zajicek G. What is a disease? The Cancer J 4, 296,1991.
7. From Gaia to Selfish Genes. Barlow C. Editor The MIT Press Cambridge MA,
1991.
8. Bocci V. The neglected organ: bacterial flora has a crucial immunostimulatory
role. Persp Biol Med 35, 251-260, 1992.