them all, perhaps , only a few bas ic kinds of injuries to the cell are responsible. Here and there,
in research widely scattered and sometimes not undertaken as a cancer study at all, we see
glimmerings of the first light that may one day illuminate this problem.
Again we find that only by looking at some of the smallest units of life, the cell and its
chromos omes , can we find that wider vis ion needed to pe netrate s uch mys teries. Here, in this
microcos m, we mus t look for thos e factors that s omehow s hift the marvelous ly functioning
mechanis ms of the cell out of their normal patte rns. One of the most impressive theories of the
origin of cancer cells was developed by a German biochemis t, Profes s or Otto Warburg of the
Max Planck Institute of Cell Physiology. Warburg has devoted a lifetime of study to the complex
proces s es of oxidation within the cell. Out of this broad background of unde rs tanding came a
fascinating and lucid explanation of the way a normal cell can become malignant. Warburg
believes that either radiation or a chemical carcinogen acts by destroying the res piration of
normal cells , thus depriving them of energy. This action may res ult from minute dos es often
repeated. The effect, once achieved, is irreversible. The cells not killed outright by the impact of
s uch a res piratory pois on s truggle to compens ate for the los s of energy. They can no longer
carry on that extraordinary and efficient cycle by which vas t amounts of ATP are produced, but
are thrown back on a primitive and far less efficient method, that of fermentation. The struggle
to s urvive by ferme ntation continues for a long period of ti me. It conti nues through ens uing cell
divis ions , s o that all the des cendant cells have this abnormal method of respiration. Once a cell
has lost its normal respiration it cannot regain it—not in a year, not in a decade or in many
decades. But little by little, in this grueling struggle to restore lost energy, those cells that
s urvive begin to compe ns ate by increas ed fermentation. It is a Darwinian s truggle, in which only
the most fit or adaptable survive. At last they reach the point where fermentation is able to
produce as much energy as res piration. At this point, cancer cells may be said to have been
created from normal body cells.
Warburg’s theory explains many otherwis e puzzling things. The long latent pe riod of mos t
cancers is the time required for the infinite numbe r of cell divis ions during which fermentation
is gradually increasing after the initial damage to res piration. The time re quire d for
ferme ntation to become dominant varies in different s pecies becaus e of different fermentation
rates: a short time in the rat, in which cancers appear quickly, a long time (decades even) in
man, in whom the development of malignancy is a deliberate process.
The Warburg theory also explains why repeated small doses of a carcinogen are more
dangerous unde r s ome circumstances than a single large dose. The latter may kill the cells
outright, whereas the small doses allow some to s urvive, though in a damaged conditi on. Thes e
survivors may then develop into cancer cells. This is why there is no ‘safe’ dose of a carcinogen.
In Warburg’s theory we als o find explanation of an otherwis e incompre hens ible fact—that one
and the s ame agent can be us eful in treating cancer and can als o caus e it. This , as everyone
knows , is true of radiation, which kills cancer cells but may also cause cancer. It is also true of
many of the che micals now us ed agains t cancer. Why? Both ty pes of agents damage
respiration. Cancer cells already have a defective respiration, so with additional damage they
die. The normal cells, suffering respiratory damage for the first time, are not killed but are set
on the path that may eventually lead to malignancy.
Warburg’s ideas received confirmation in 1953 when othe r workers were a ble to turn normal
cells into cancer cells merely by depriving them of oxygen intermittently over long periods.
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