The Prime Cause and Prevention of Cancer
with two prefaces on prevention
Revised lecture at the meeting of the Nobel-Laureates on June 30, 1966
at Lindau, Lake Constance, Germany
Otto Warbugh Director, Max Planck-Institute for Cell Physiology, Berlin-Dahlem
English Edition by Dean Burk
National Cancer Institute, Bethesda, Maryland, USA
The Second Revised Edition
Published by Konrad Triltsch, Würzburg, Germany 1969
Preface to the Second Revised German Edition of the Lindau Lecture
(The way to prevention of cancer)
Since the Lindau lecture of June 1966 many physicians have examined - not
unsuccessfully - the practical consequences of the anaerobiosis of cancer
cells. The more who participate in these examinations, the sooner will we
know what can be achieved. It is a unique aspect of these examinations that
they can be carried out on human patients, on the largest scale, without
risk; whereas experiments on animals have been misleading many times. The
cure of human cancer will be the resultant of biochemistry of cancer and
of biochemistry of man.
A list of selected active groups of respiratory enzymes will soon be published,
to which we recently added cytohemin and d-amino-Levulinic acid, the precursor
of oxygen-transferring hemins. In the meantime commercial vitamin preparations
may be used that contain, besides other substances, many active groups of
the respiratory enzymes. Most of these may be added to the food. Cytohemin
and vitamin B 12 may be given subcutaneously. (A synonym of "active group"
is prosthetic" group of an enzyme.)
There exists no alternative today to the prevention of cancer as proposed
at Lindau. It is the way that attacks the prime cause of cancer most directly
and that is experimentally most developed. Indeed millions of experiments
in man, through the effectiveness of some vitamins, have shown, that cell
respiration is impaired if the active groups of the respiratory enzymes are
removed from the food; and that cell respiration is repaired at once, if
these groups are added again to the food. No way can be imagined that is
scientifically better founded to prevent and cure a disease, the prime cause
of which is an impaired respiration. Neither genetic codes of anaerobiosis
nor cancer viruses are alternatives today, because no such codes and no such
viruses in man have been discovered so far; but anaerobiosis has been
What can be achieved by the active groups, when tumors have already developed?
The answer is doubtful, because tumors live in the body almost anaerobically,
that is under conditions that the active groups cannot act.
On the other hand, because young metastases live in the body almost aerobically,
inhibition by the active groups should be possible. Therefore we propose
first to remove all compact tumors, which are the anaerobic foci of the
metastasis. Then the active group should be added to the food, in the greatest
possible amount, for many years, even for ever. This is a promising task.
If it succeeds, then cancer will be a harmless disease.
Moreover, we discovered recently a) in experiments with growing cancer cells
in vitro that very low concentrations of some selected active groups inhibit
fermentation and the growth of cancer cells completely, in the course of
a few days. From these experiments it may be concluded that de-differentiated
cells die if one tries to normalize their metabolism. It is a result that
is unexpected and that encourages the task of inhibiting the growth of metastases
with active enzyme groups.
a) In press in Hoppe-Seylers Zeitschrift für Physiologische Chemie 1967.
10 g riboflavin per ccm or 10 g d-Aminolevulinic acid inhibit in vitro growth
and fermentation completely but inhibit respiration less. As expected, ascites
cancer in vivo is not cured.
As emphasized, it is the first precondition of the proposed treatment that
all growing body cells be saturated with oxygen. It is a second precondition
that exogenous carcinogens be kept away, at least during the treatment. All
carcinogens impair respiration directly or indirectly by deranging capillary
circulation, a statement that is proved by the fact that no cancer cell exists,
the respiration of which is not impaired. Of course, respiration cannot be
repaired if it is impaired at the same time by carcinogens.
It has been asked after the Lindau lecture why the repair of respiration
by the active groups of the enzymes was proposed as late as 1966, although
the fermentation of the cancer cell was discovered as early as 1923. Why
was so much time lost?
He who asked this questions ignored that in 1923 the chemical mechanism of
enzyme action was still a secret of living nature alone1). The first active
group of an enzyme, "Iron, the Oxygen-Transferring Part of the Respiratory
Enzyme" was discovered in 19242). There followed in two decades the discoveries
of the O2-transferring metalloproteins, the flavoproteins and the
pyridinproteins, a period that was concluded by the "Heavy Metals as Prosthetic
Groups of Enzymes"3) and by the "Hydrogen Transferring Enzymes"4) in 1947
Moreover, during the first decades after 1923 glycolysis and anaerobiosis
were constantly confused, so that nobody knew what was specific for tumors.
The three famous and decisive discoveries of DEAN BURK and colleagues5) of
the National Cancer Institute at Bethesda were of the years 1941, 1956 and
1964: first, that the metabolism of the regenerating liver, which grows more
rapidly than most tumors, is not cancer metabolism, but perfect aerobic embryonic
metabolism; second, that cancer cells, descended in vitro from one single
normal cell, were in vivo the more malignant, the higher the fermentation
rate; third, that in vivo growing hepatomas, produced in vivo by different
carcinogens, were in vivo the more malignant, the higher the fermentation
rate. - Furthermore, the very unexpected and fundamental fact, that tissue
culture is carcinogenic and that a too low oxygen pressure is the intrinsic
cause were discovered6-8) in the years 1927 to 1966. - Anaerobiosis of cancer
cells was an established fact only since 1960 when methods were developed7)
to measure the oxygen pressure inside of tumors in the living body.
This abridged history shows that even the greatest genius would not have
been able to propose in 1923, what was proposed at Lindau in 1966. As unknown
as the prime cause of cancer was in 1923 was the possibility to prevent it.
Life without oxygen in a living world that has been created by oxygen 9)
was so unexpected that it would have been too much to ask that anaerobiosis
of cancer cells should be accepted at once by all scientists. But most of
the resistance disappeared when at Lindau it was explained that on the basis
of anaerobiosis there is now a real chance to get rid of this terrible disease,
if man is willing to submit to experiments and facts. It is true that more
than 40 years were necessary to learn how to do it. But 40 years is a short
time in the history of science10).
Wiesenhof über Idar-Oberstein, August 1967 OTTO WARBURG
Two years after the Lindau lecture LINUS PAULING (Science Vol. 160, Page
265, 1968) proposed to control mental diseases by adding to the food the
active groups of respiratory enzymes. But here the experimental basis was
lacking. No mental disease is known so far, the prime cause of which is an
impairment of the respiration of brain cells.
Preface to the First edition
(Prevention of endogenous cancer)
Most experts agree that nearly 80% of cancers could be prevented, if all
contact with the known exogenous carcinogens could be avoided. But how can
the remaining 20%, the endogenous or so-called spontaneous cancers, be prevented?
Because no cancer cell exists, the respiration of which is intact1 , it cannot
be disputed that cancer could be prevented if the respiration of the body
cells would be kept intact.
Today we know two methods to influence cell respiration. The first is to
decrease the oxygen pressure in growing cells. If it is so much decreased
that the oxygen transferring enzymes are no longer saturated with oxygen,
respiration can decrease irreversibly and normal cells can be transformed
into facultative anaerobes.
The second method to influence cell respiration in vivo is to add the active
groups of the respiratory enzymes to the food of man. Lack of these groups
impairs cell respiration and abundance of these groups repairs impaired cell
respiration - a statement that is proved by the fact that these groups are
necessary vitamins for man. To prevent cancer it is therefore proposed
first to keep the speed of the blood stream so high that the venous blood
still contains sufficient oxygen; second, to keep high the concentration
of hemoglobin in the blood; third to add always to the food, even of healthy
people, the active groups of the respiratory enzymes; and to increase the
doses of these groups, if a precancerous state has already developed. If
at the same time exogenous carcinogens are excluded rigorously, then most
cancers may be prevented today.
These proposals are in no way utopian. On the contrary, they may be realized
by everybody, everywhere, at any hour. Unlike the prevention of many other
diseases the prevention of cancer requires no government help, and no extra
Wiesenhof, August 1966 OTTO WARBURG
The Prime Cause and Prevention of Cancer
(Revised Lindau Lecture)
By OTTO WARBURG
(Director, Max Planck Institute for Cell Physiology, Berlin-Dahlem, Germany)
English Edition by DEAN BURK*), National Cancer Institute, Bethesda, Maryland
*) Note by DEAN BURK: Adapted from a lecture originally delivered by O. Warburg
at the 1966 annual meeting of Nobelists at Lindau, Germany. O. Warburg won
the Nobel Prize in Medicine in 1931 for his discovery of the oxygen transferring
enzyme of cell respiration, and was voted a second Nobel Prize in 1944 for
his discovery of the active groups of the hydrogen transferring enzymes.
Many universities, like Harvard, Oxford, Heidelberg have offered him honorary
degrees. He is a Foreign member of the Royal Society if London, a Knight
of the Order of Merit founded by Frederick the Great, and was awarded the
Great Cross with Star and Shoulder ribbon of the Bundesrepublik. His main
interests are Chemistry and Physics of Life. In both fields no scientists
has been more successful.
There are prime and secondary causes of diseases. For example, the prime
cause of the plaque is the plaque bacillus, but secondary causes of the plaque
are filth, rats, and the fleas that transfer the plaque bacillus from rats
to man. By a prime cause of a disease I mean one that is found in every case
of the disease.
Cancer, above all other diseases, has countless secondary causes. But, even
for cancer, there is only one prime cause. Summarized in a few words, the
prime cause of cancer is the replacement of the respiration of oxygen in
normal body cells by a fermentation of sugar. All normal body cells meet
their energy needs by respiration of oxygen, whereas cancer cells meet their
energy needs in great part by fermentation. All normal body cells are thus
obligate aerobes, whereas all cancer cells are partial anaerobes. From the
standpoint of the physics and chemistry of life this difference between normal
and cancer cells is so great that one can scarcely picture a greater difference.
Oxygen gas, the donor of energy in plants and animals is dethroned in the
cancer cells and replaced by an energy yielding reaction of the lowest living
forms, namely, a fermentation of glucose.
The key to the cancer problem is accordingly the energetics of life, which
has been the field of work of the Dahlem institute since its initiation by
the Rockefeller Foundation about 1930. In Dahlem the oxygen transferring
and hydrogen transferring enzymes were discovered and chemically isolated.
In Dahlem the fermentation of cancer cells was discovered decades ago; but
only in recent years has is been demonstrated that cancer cells can actually
grow in the body almost with only the energy of fermentation. Only today
can one submit, with respect to cancer, all the experiments demanded by PASTEUR
and KOCH as proof of the prime causes of a disease. If it is true that the
replacement of oxygen-respiration by fermentation is the prime cause of cancer,
then all cancer cells without exception must ferment, and no normal growing
cell ought to exist that ferments in the body.
An especially simple and convincing experiment performed by the Americans
MALMGREN and FLANEGAN confirms the view. If one injects tetanus spores, which
can germinate only at very low oxygen pressures, into the blood of healthy
mice, the mice do not sicken with tetanus, because the spores find no place
in the normal body where the oxygen pressure is sufficiently low. Likewise,
pregnant mice do not sicken when injected with the tetanus spores, because
also in the growing embryo no region exists where the oxygen pressure is
sufficiently low to permit spore germination. However, if one injects tetanus
spores into the blood of tumor-bearing mice, the mice sicken with tetanus,
because the oxygen pressure in the tumors can be so low that the spores can
germinate. These experiments demonstrate in a unique way the anaerobiosis
of cancer cells and the non-anaerobiosis of normal cells, in particular the non-anaerobiosis of growing embryos.
The Fermentation of Morris Hepatomas
A second type of experimentation demonstrates a quantitative connection between
fermentation of tumors and growth rate of tumors.
If one injects rats with cancer-inducing substances of different activities,
one can create, as HAROLD MORRIS of the National Cancer Institute in Bethesda
has found, liver cancers (hepatomas) of very different degrees of malignancy.
Thus, one strain of tumor may double its mass in three days, another strain
may require 30 days. Recently DEAN BURK and MARK WOODS 3), also of the National
Cancer Institute, measured the in vitro rates of anaerobic fermentation in
different lines of these hepatomas, and obtained a curve (Fig. 1) that shows
a quantitative relationship between fermentation and growth rate, and therefore
between fermentation and malignancy, in these various tumor strains. The
fermentation increases with the malignancy, and indeed the fermentation increases
even faster than the malignancy.
Special interest attaches to the fermentation of the most slowly growing
hepatomas, because several investigators in the United States believed that
they had found *) that such tumors had no fermentation; that is that anaerobiosis
cannot be the prime cause of cancer.
*) For example see C. H. BÖHRINGER SON, Ingelheim am Rhein, the factory
Work-Journal "Das Medizinische Prisma" , Vol. 13, 1963. Here a lecture of
VAN POTTER (Madison, Wisconsin) is reprinted where owing to the slow-growing
Morris-tumors anaerobiosis as prime cause of cancer is rejected and the lack
of "intracellular feeding back" is claimed to be the real cause of cancer.
Fig. 1. Velocity of growth and fermentation of the Morris-Hepatomas, according
to DEAN BURK and MARK WOODS
DEAN BURK and MARK WOODS saw immediately from their curves that in the region
of the zero point the rate of fermentation was so small that it could no
longer be measured by the usual gross methodology employed by the aforementioned
workers, whereas in the same region the smallest growth rate was always easily
measurable. BURK and WOODS saw, in other words, that in the region of the
zero pint of their curves the growth test was more sensitive than the usual
fermentation test. With refined and adequate methods for measuring fermentation
of sugar (glucose) they found, what any physical chemist after a glance at
the curve would realize, that even the most slow-growing Morris hepatomas
The results of DEAN BURK and MARK WOODS were confirmed and extended by other
workers with independent methods. PIETRO GULLINO, also in Bethesda, developed
a perfusion method whereby a Morris hepatoma growing in the living animal
could be perfused for long periods of time, even weeks, by means of a single
artery and single vein, and the blood entering and leaving any given tumor
could be analyzed. GULLINO found with this method that the slow-growing Morris
hepatomas always produced fermentation lactic acid during their growth. This
was in contrast to liver, where, as known since the days of CLAUDE BERNARD,
lactic acid is not produced but consumed by liver; the difference between
liver and Morris tumors in vivo is thus infinite (+ vs. -). GULLINO further
found that tumors grow in vivo with diminished oxygen consumption. In summary,
GULLINO's findings indicate that the slow-growing Morris hepatomas are partial
anaerobes. SILVIO FIALA, a biochemist at the University of Southern California,
found that not only did the slow-growing hepatomas produce lactic acid, but
also that the number of their oxygen-respiring grana was reduced.
The slow-growing Morris hepatomas are therefore far removed from having refuted
the anaerobiosis of tumors. On the contrary, they are the best proof of this
distinctive characteristic. For forty years cancer investigators have searched
for a cancer that did not ferment. When finally a non-fermenting tumor appeared
to have been found in the slow-growing Morris tumors, it was shown to be
a methodological error.
Transformation of Embryonic Metabolism into Cancer Metabolism
A third type of experiment, from the institute in Dahlem with coworkers GAWEHN,
GEISSLER and LORENZ, is likewise highly pertinent. Having established that
anaerobiosis is that property of cancer cells that distinguishes them from
all normal body cells, we attacked the question, namely, how normal body
cells may become transformed into anaerobes 6)7)8).
If one puts embryonic mouse cells into a suitable culture medium saturated
with physiological oxygen pressures, they will grow outside the mouse body,
in vitro, and indeed as pure aerobes, with a pure oxygen respiration, without
a trace of fermentation. However, if during the growth one provides and oxygen
pressure so reduced that the oxygen respiration is partially inhibited, the
purely aerobic metabolism of the mouse embryonic cells is quantitatively
altered within 48 hours, in the course of two cell divisions, into the metabolism
characteristic of fermenting cancer cells. Fig. 2 illustrates the very simple
experimental procedure involved.
If one then brings such cells, in which during their growth under reduced
oxygen pressure a cancer cell metabolism has been produced, back under the
original high oxygen pressure, and allows the cell to grow further, the cancer
metabolism remains. The transformation of embryonic cell metabolism into
cancer cell metabolism can thus be irreversible, and important result, since
the origin of cancer cells from normal body cells is an irreversible process.
It is equally important that these body cells whose metabolism has thus been
transformed into cancer metabolism now continue to grow in vitro as facultative
anaerobes. The duration of our experiments is still too limited to have yielded
results of tests of inoculation of such cells back into mice, but according
to all previous indications such cells will later grow as anaerobes upon
transplantation into animals.
In any case, these experiments belong to the most important experiments in
the field of cancer investigation since the discovery of the fermentation
of tumors. For cancer metabolism, heretofore, measured so many thousand of
times, has now been induced artificially in body cells by the simplest
conceivable experimental procedure, and with this artificially induced cancer
metabolism the body cells divide and grow as anaerobes in vitro*).
*) The experiments were at once repeated, when they were published, of course
without acknowledgment. See for example Th. Goodfriend, D. M. Sokol and N.
O. Kaplan, J. molecular Biol. 15, 18, 1966.
In recent months we have further developed our experimental arrangements
so that we can measure manometrically the oxygen respiration and fermentation
of the growing mouse embryonic cells during the metabolic transformation.
Fig. 3 shows the experimental arrangement. We find by such experiments that
35 percent inhibition of oxygen respiration already suffices to bring about
such a transformation during cell growth**). Oxygen pressures that inhibit
respiration 35 percent can occur at the end of blood capillaries in living
animals, so that the possibility arises that cancer may result when too low
oxygen pressures occur during cell growth in animal bodies.
**) These experiments show, like the curve of Dean Burk and Mark Woods in
Fig. 1, that it is more correct to designate tumor cells as "partial anaerobes"
rather than "facultative anaerobes". A body cell is transformed into a tumor
cell if only a part of the respiration is replaced by fermentation.
Fig. 2. Method to transform embryonic metabolism into cancer metabolism by
decreasing the oxygen pressure
The induction of cancers by solid materials injected into animals is a further
experimental indication of this possibility. If one implants discs of solid
substances under the skin of rats, the discs will soon be surrounded by capsules
of living tissue that will be nourished with blood vessels from the hypodermis.
Sarcomas very frequently develop in these capsules. It is immaterial whether
the solid discs are chemically plastics, gold, or ivory, etc. What produces
the cancer is not the chemical nature of the solid discs, but the special
king of blood nourishment supplied to the tissue encapsulating the discs.
This blood provision varies with the site and in adequacy within a given
animal, and induces cancer from the low oxygen pressure in the encapsulating
Fig. 3. Method to measure manometrically respiration and fermentation during
the transformation of embryonic into cancer metabolism*)
*) The vessels are not shaken, because shaking inhibits growth. Therefore,
the oxygen pressure in the liquid phase at the bottom of the vessels is much
lower than in the gasphase. For example, when the oxygen pressure in the
gas phase was 2000 mm H2O it was at the bottom of the vessels 130 mm H2O.
(O. Warburg, A. Geissler and S. Lorenz, Zeitschr. Für Naturforschung
20b, 1070, 1965.)
If a lowered oxygen pressure during cell growth may cause cancer, or, more
generally, if any inhibition of respiration during growth may cause cancer,
then a next problem is to show why reduced respiration induces cancer. Since
we already know that with a lowering of respiration fermentation results,
we can re-express our question: Why does cancer result if oxygen-respiration
is replaced by fermentation?
The early history of life on our planet indicates that life existed on earth
before the earth's atmosphere contained free oxygen gas. The living cells
must therefore have been fermenting cells then, and, as fossils show, they
were undifferentiated single cells. Only when free oxygen appeared in the
atmosphere - some billion years ago - did the higher development of life
set in, to produce the plant and animal kingdoms from the fermenting,
undifferentiated single cells. What the philosophers of life have called
"Evolution créatrice" has been and is therefore the work of oxygen.
The reverse process, the dedifferentiation of life, takes place today in
greatest amount before our eyes in cancer development, which is another
expression for dedifferentiation. To be sure, cancer development takes place
even in the presence of free oxygen gas in the atmosphere, but this oxygen
may not penetrate in sufficient quantity into the growing body cells, or
the respiratory apo-enzymes of the growing body cells may not be saturated
with the active groups. In any case, during the cancer development the
oxygen-respiration always falls, fermentation appears, and the highly
differentiated cells are transformed to fermenting anaerobes, which have
lost all their body functions and retain only the now useless property of
growth. Thus, when respiration disappears, life does not disappear, but the
meaning of life disappears, and what remains are growing machines that destroy
the body in which they grow.
But why oxygen differentiates and why lack of oxygen dedifferentiates? Nobody
would dispute that the development of plants and animals and man from unicellular
anaerobes is the most improbable process of all processes in the world. Thus
there is no doubt, that EINSTEIN descended from a unicellular fermenting
organism - to illustrate the miracle, molecular O2 achieved. But according
to the thermodynamics of Boltzmann, improbable processes require work to
take place. It requires work to produce temperature differences in a uniformly
temperatured gas; whereas the equalization of such temperature differences
is a spontaneous process that does not require work. It is the oxygen-respiration
that provides in life this work, and dedifferentiation begins at once when
respiration is inhibited in any way. In the language of thermodynamics,
differentiation represents a forced steady state, whereas dedifferentiation
- that is, cancer - is the true equilibrium state. Or, illustrated by a picture:
the differentiated body cell is like a ball on an inclined plane, which,
would roll down except for the work of oxygen-respiration always preventing
this. If oxygen respiration is inhibited, the ball rolls down the plane to
the level of dedifferentiation.
But why respiratory energy and not fermentation energy can differentiate,
whereas in general, for example in growth, respiratory energy and fermentation
energy are equivalent? Obviously, there would be no cancer if there were
not this discrimination of fermentation energy, that is, if fermentation
like respiration could differentiate. Then, when respiration is replaced
by fermentation, fermentation would take over differentiation, and a high
state of differentiation would be maintained even in the fermenting body
Physics cannot explain why the two kinds of energy are not equivalent in
differentiation; but chemistry may explain it. Biochemists know that both
respiration energy and fermentation energy do their work as phosphate energy,
but the ways of phosphorylation are different. If one applies this knowledge
to carcinogenesis, it seems that only oxidative phosphorylation but not
fermentative phosphorylation can differentiate, a result, that may in future
explain the mechanism of differentiation.
Yet Biochemistry can explain already today why fermentation arises, when
respiration decreases. Figure 4 shows that the pathways of respiration and
fermentation are common as far as pyruvic acid. Then the pathways diverge.
The endproducts of fermentation is reached by one single reaction, the reduction
of pyruvic acid by dihydro-nicotinamide to lactic acid. On the other hand,
the endproducts of the oxidation of pyruvic acid, H2O and CO2, are only reached
after many additional reactions. Therefore, when cells are harmed, it is
probable that first respiration is harmed.
In this way the frequency of cancer is explained by reasons of probability.
To sum up:
1. Impairment of respiration is frequent than impairment of fermentation
because respiration is more complicated than fermentation.
2. The impaired respiration can be easily replaced by fermentation, because
both processes have a common catalyst, the nicotinamide.
3. The consequence of the replacement of respiration by fermentation is mostly
glycolysis, with death of the cells by lack of energy. Only if the energy
of fermentation is equivalent to the lost energy of respiration, is the
consequence anaerobiosis. Glycolysis means death by fermentation, anaerobiosis
means life by fermentation.
4. Cancer arises, because respiration, but not fermentation, can maintain
and create the high differentiation of body cells.
To conclude the discussion on the prime cause of cancer, the virus-theory
of cancer may be mentioned. It is the most cherished topic of the philosophers
of cancer. If it were true, it would be possible to prevent and cure cancer
by the methods of virology; and all carcinogens could be eaten or smoked
freely without any danger, if only contact with the cancer virus would be
It is true that some virus-caused cancer b) occur in animals, but no one
sure human virus-cancer has been observed so far, whereas innumerable substances
cause cancer without viruses in animals and man. Thus viruses do not meet
the demands of Pasteur, that is must be possible to trace the prime cause
in every case of the disease. Therefore science classifies viruses as remote
causes of cancer, leading to anaerobiosis, the prime cause, that meets the
demands of Pasteur.
b) The chicken Rous sarcoma, which is labeled today as a virus tumor, ferments
glucose and lives as a partial anaerobe like all tumors. O. WARBURG, Bioch.
Zeitschrift 160, 307, 1925; F. WIND, Klinische Wochenschrift, Nr. 30, 1926.
Many may remember how anaerobiosis as prime cause of cancer was recently
disputed emphatically, when one single cancer - the slow Morris hepatomas
- was believed (wrongly) to lack in fermentation. In contrast the virus theory
is adhered to although all cancers of man are lacking in virus-origin. This
means the surrender of the principles of Pasteur and the relapse into bygone
times of medicine.
Of what use is it to know the prime cause of cancer? Here is an example.
In Scandinavian countries there occurs a cancer of throat and esophagus whose
precursor is the so-called Plummer-Vinson syndrome. This syndrome can be
healed when one adds to the diet the active groups of respiratory enzymes,
for example: iron salts, riboflavin, nicotinamide, and pantothenic acid.
When one can heal the precursor of a cancer, one can prevent this cancer.
According to ERNEST WYNDER 3) of the Sloan-Kettering Institute for Cancer
Research in New York, the time has come when one can exterminate this kind
of cancer with the help of the active groups of the respiratory enzymes.
It is of interest in this connection that with the help of one of these active
groups of the respiratory enzymes, namely nicotinamide, tuberculosis can
be healed quite as well as with streptomycin, but without the side effects
of the latter c). Since the sulfonamides and antibiotics, this discovery
made in 1945 is the most important event in the field of chemotherapy generally,
and encourages, in association with the experiences in Scandinavia, efforts
to prevent cancer by dietary addition of large amounts of the active groups
of the respiratory enzymes. Since there can scarcely be overdosage, such
experiments can do no harm.
c) V. CHORINE: C. R. sci. Paris, 220, 150 (1945). - H. FUST and A. STUDER,
Schweizerische Z. für allgemeine Pathologie, Band 14; Fasc 5 (1951).
I would like to go further and propose always making dietary additions of
large amounts of the active groups of the respiratory enzymes after successful
operations when there is danger from metastatic growths. One could indeed
never succeed in redifferentiating the dedifferentiated cancer cells, since
during the short duration of human life the probability of such a
back-differentiation is zero. But one might increase the respiration of growing
metastases, and thereby inhibit their fermentation, and - on the basis of
the curve of DEAN BURK and MARK WOODS obtained with the Morris hepatomas
- thereby inhibit the growth of metastases to such an extent that they might
become as harmless as the so-called "sleeping" cancer cells in the prostates
of elderly men.
A Second Example of Application
The physicist MANFRED VON ARDENNE has recently attacked the problem of the
therapy of cancer. ARDENNE discovered that cancer cells owing to their
fermentation, are more acid - inside and on their surface - than normal cells
and hence are more sensitive to high temperatures. On this basis, he and
his medical colleagues have treated cancer patients, after surgical removal
of the primary tumors, by raising the body temperature of the patients to
about 109º Fahrenheit for an hour, in the hope that the metastases will
then be killed or their growth so slowed up as to become harmless. It is
not yet decided whether this idea can be described as a practical success.
But the provisional work of ARDENNE is already of great significance in a
field where hopes of conventional chemotherapy have been dimmed but might
be brightened by combination with extreme or moderate hyperthermy.
A third application. According to an estimate by K. H. Bauer of the Cancer
Institute in Heidelberg, at least one million of the now living twenty five
million male inhabitants of West Germany will die of cancer of the respiratory
tract; still more will die from other cancer. When one considers that cancer
is a permanent menace, one realizes that cancer has become one of the most
dangerous menaces in the history of medicine.
Many experts agree that one could prevent about 80% of all cancers in man,
if one could keep away the known carcinogens from the normal body cells.
This prevention of cancer might involve no expenses, and especially would
require little further research to bring about cancer prevention in up to
80 percent *).
*) Since this estimate was published, some though 80% even to low. Yet prevention
remained taboo and early diagnosis was the only consolation that was offered.
Why then does it happen that in spite of all this so little is done towards
the prevention of cancer? The answer has always been that one does not know
what cancer or the prime cause of cancer be, and that one cannot prevent
something that is not known.
But nobody today can say that one does not know what cancer and its prime
cause be. On the contrary, there is no disease whose prime cause is better
known, so that today ignorance is no longer an excuse that one cannot do
more about prevention. That prevention of cancer will come there is no doubt,
for man wishes to survive. But how long prevention will be avoided depends
on how long the prophets of agnosticism will succeed in inhibiting the
application of scientific knowledge in the cancer field. In the meantime,
millions of men must die of cancer unnecessarily.
Literature to Preface of Second Edition:
1. WILLSTAETTER, WIELAND and EULER, Lectures on enzymes at the centenary
of the Gesellschaft Deutscher Naturforscher. Berichte der Deutschen Chemischen
Gesellschaft, 55, 3583, 1922. The 3 lectures of the 3 chemists show that
in the year 1922 the action of all enzymes was still a mystery. No active
group of any enzyme was known.
2. OTTO WARBURG, Biochem. Zeitschrift, 152, 479, 1924.
3. OTTO WARBURG, Heavy Metals as prosthetic groups of enzymes, Clarendon
Press, Oxford, 1949.
4. OTTO WARBURG, Wasserstoffübertragende Fermente, Verlag Werner
Sänger, Berlin, 1948.
5. DEAN BURK, 1941. On the specificity of glycolysis in malignant liver tumors
as compared with homologous adult or growing liver tissues. In Symposium
of Respiratory Enzymes, Univ. of Wisconsin Press. pp. 235-245,1942. DEAN
BURK, Science 123,314,1956. Woods, M. W., Sandford, K. K., Burk, D., and
Earle, W. R. J. National Cancer Institute 23, 1079-1088, 1959. DEAN BURK,
Burk, D., Woods, M. and Hunter, J. On the Significance of Glucolysis for
Cancer Growth, with Special Reference to Morris Rat Hepatomas. Journ. National
Cancer Institute 38, 839-863, 1967.
6. O. WARBURG und F. KUBOWITZ, Bioch. Z. 189, 242, 1927; H. GOLDBLATT und
G. CAMERON, J. Exper. Med. 97, 525, 1953.
7. O. WARBURG, 17. Mosbacher Kolloquium, April 1966. Verlag Springer, Heidelberg,
8. O. WARBURG, K. GAWEHN, A. W. GEISSLER, D. KAYSER and S. LORENZ, Klinische
Wochenschrift 43, 289, 1965.
9. O. WARBURG, Oxygen, The Creator of Differentiation, Biochemical Energetics,
Academic Press, New York, 1966.
10. O. WARBURG, New Methods of Cell Physiology, Georg Thieme, Stuttgart,
and Interscience Publishers, New York, 1962.
Literature to Preface of First Edition:
1. OTTO WARBURG, A. W. GEISSLER, and S. LORENZ: Über die letzte Ursache
und die entfernten Ursachen des Krebses. 17. Mosbacher Kolloquium, April
1966. Verlag Springer, Heidelberg 1966.
2. Any book on vitamins, such as Th. Bersin. Biochemie der Vitamine. Akad.
Verlags.-Ges. Frankfurt 1966.
3. ERNEST L. WYNDER, SVEN HULTBERG, FOLKE JACOBSSON, and IRWIN J. BROSS,
Environmental Factors in Cancer. Cancer, Vol. 10, 470, 2057.