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578 THE SCIENTIFIC MONTHLY

NATURAL DEATH AND THE DURATION

OF LIFE
By Dr. JACQUES LOEB
THE ROCKEFELLER INSTITUTE FOR MEDICAL RESEARCH

I
HE efforts to prolonglife have resulted in a diminutionof
the chances of premature death. Nations with ade-
quately developed facilities for medical research and an effi-
cient public health service have practically eliminated smallpox
and typhoid, yellow fever and malaria, and have conquered
rabies, diphtheria, tetanus, and cerebrospinal meningitis. If
this development continues to receive the support it deserves,
the time is bound to come when each human being can be
guaranteed with a fair degree of probability a full duration of
life. But why must we die?
The French encyclopedists of the eighteenth century defined
life as that which resists death. What they meant by this defini-
tion was the fact that as soon as death sets in, the body begins
to disintegrate. They argued correctly that the forces of dis-
integration were inherent in the living body but were held in
check during life. Recent progress in physical chemistry per-
mits us to state that the spontaneous disintegration of the body
which sets in with death (at the proper temperature and proper
degree of moisture) is a process of digestion, comparable to
that which the meat we eat undergoes in our stomach and intes-
tine. The essential feature of digestion is in this case the
transformation of the solid meat into soluble products by two
ferments, pepsin, which exists in the stomach, and trypsin,
which exists in the intestine. The successive treatment of meat
by the two ferments results in the breaking-up of the large
insoluble molecules into the small soluble molecules of amino
acids which are absorbed by the blood and carried to the cells
of the body where they are utilized to build up new solid
cell matter.
These two ferments, pepsin and trypsin, exist not only in
the digestive organs, but in many, and possibly in all living
cells, and the question arises, why they do not constantly digest
and thus destroy our body while life lasts. A tentative answer
 NATURAL DEAT T H79

to this question has been given by Dernby, who has been able
to show that the cooperation of both ferments is required in
the same cell for the work of destruction, and that this co-
operation of both ferments becomes possible only at a certain
degree of acidity, which cannot be reached in the living body
on account of the constant removal of acid through respiration
and oxidation. When respiration ceases, the degree of acidity
necessary for the digestive action of both ferments in the same
cell is reached, leading to gradual digestion and liquefaction of
the tissues which characterizes the disintegration of the
dead body.
This is not the only cause of disintegration, since the dead
body becomes also the prey of the destructive action of micro-
organisms from the air and in the intestine. During life these
same microorganisms are powerless in their attack on the cells
protected by a normal membrane, but after death this mem-
brane is destroyed and the action of microorganisms can super-
impose itself on that of digestion. It is also probable that the
normal secretions of the mucous membranes during life have
a protective effect.
Death, then, in a human being means the permanent cessa-
tion of respiration. We know that this result can be brought
about by mechanical violence, by poison, and by disease, and,
since nobody can escape all these agencies, doubts have arisen
whether we do not all die from injury or disease, and whether
such a thing as natural death really exists. If there were no
natural death it should be possible to prolong life indefinitely
if a complete protection against disease and accidents could be
secured. It is impossible to make such an experiment in a
human being, since our intestine and our respiratory tract
can not be kept free from microorganisms. The problem has,
however, been solved for certain insects. A Russian author,
Bogdanow, invented a method of obtaining the common house-
fly free from all microorganisms, by putting the newly laid
eggs for a number of minutes into a solution of bichloride of
mercury of sufficient concentration. Most eggs were killed in
the process, but some survived and these were free from micro-
organisms at their surface. By keeping the eggs on sterilized
meat and in sterile flasks, the maggots leaving the egg could
find their food and develop into flies. A French author,
Guyenot, continuing the experiments on the fruit fly, raised 80
successive aseptic generations, and Northrop and the writer
have raised thus far 87 aseptic successive generations of the
580 THE SCIENTIFIC MONTHLY

fruit fly on aseptic yeast. In these experiments all possibility

of infection, all chances of accidental or violent death were ex-
cluded. To make sure that these flies are absolutely free from
microorganisms, their dead bodies are transferred to culture
media such as are used for the growth of bacteria. If a common
fruit fly is put on such a culture medium, in 24 hours a rapid
growth of microorganisms develops, while the culture medium
on which our aseptic flies were put remained free from all
growth for years (or rather permanently). Aseptic fruit flies,
free from infectious disease and supplied with proper food will,
therefore, not escape death. These experiments, then, indicate
that higher organisms must die from internal causes even if all
chance of infection and all accidents are excluded.

II
These aseptic flies served as a means for testing an idea
concerning the duration of life which presented itself, namely,
that old age and natural death are due either to the gradual
production in the body of a sufficient quantity of harmful or
toxic substances, or to the gradual destruction of substances in
the body required to keep it in youthful vigor, or to both. On
this basis the natural duration of life would be in reality the
time required to complete a chemical reaction or a series of
chemical reactions, resulting in the production of toxic com-
pounds in a quantity sufficient to kill, or resulting in the de-
struction of necessary compounds. Metchnikoff had called at-
tention to the fact that toxic substances were formed in the
intestines under the influence of microorganisms. The intes-
tine of aseptic flies is free from microorganisms, so that the
source for the shortening of life pointed out by Metchnikoff
need not be considered in this case. The toxic substances
formed might be substances formed in one or several organs of
the body during their normal activity. Modern physical chem-
istry furnishes the means of testing such an idea. The period
of time required to complete a chemical reaction diminishes
rapidly when the temperature is raised and increases rapidly
when the temperature is lowered. Exeriments show that the
time required for the completion of a chemical reaction is
doubled or trebled when the temperature is lowered by 100
centigrade. This influence of temperature upon the rate of
processes of nature seems to be typical for chemical reactions.
If, therefore, the duration of life is the time required for the
completion of certain chemical reactions in the body we might
 NATURAL DEATH 581

expect that the duration of life will be doubled or trebled when

we lower the temperature ten degrees centigrade. Such ex-
periments can be carried out only in organisms where acci-
dental death by infection is excluded and our aseptic fruit flies
satisfied this condition. These experiments were made by Dr.
Northrop and the writer, and consisted in putting a number of
newly laid eggs of aseptic flies on an abundance of sterilized
yeast (which is their natural food) in a flask plugged with cot-
ton. These flasks were put into incubators the temperature of
which was kept constant within 0.2 of a degree centigrade.
The temperatures selected for the purpose were 10, 15, 20, 25,
27.5, and 30? C. It is not possible to go into the numerous pre-
cautions which it was necessary to take and the many technical
difficulties involved in this investigation. The result of a large
number of experiments was that the duration of life of such
aseptic flies was a definite one for each temperature, which
means that all the flies died at practically the same age when
kept at the same temperature. Thus, for instance, the total
average duration of life of such flies was 21.15 days at 300 C.
The overwhelming majority died at that age, but a few died a
little earlier and a few a little later. When the number of flies
of a culture which die on successive days is plotted in terms of
percentage of the original number of flies, we get that curve of
death rates usually given in life insurance statistics. But this
curve is very steep in our case owing to the fact that the
majority of flies die at about the same time for a given constant
temperature. The following table gives the average duration
of life of the fly in days for different temperatures.

TABLE I
Temperature. Average Duration of Life of the
ec. Fly from Egg to Death, Days
30 21.15
25 38.5
20 54.3
15 123.9
10 177.5 + x

This table shows that the influence of temperature on the

duration of life of the fly is the same as the influence of tem-
perature on the velocity of a chemical reaction, inasmuch as a
lowering of the temperature by ten degrees results in an in-
crease in the duration of life by two or three hundred per cent.,
and the same figure would be obtained if we investigated the
effect of temperature upon the time required to complete a
chemical reaction. At 300 C. the flies live on an average 21.15
582 THE SCIENTIFIC MONTHLY

days and at 200 C. they will live on an average 54.3 days or a

little over twice as long. At 250 they live 38.5 days and at
150 C. 123.9 days or about three times as long. The fruit fly
is a tropical organism and 300 C. is not far from the optimal
temperature. By lowering their temperature twenty degrees
we prolong the duration of their life by nine hundred per cent.
We cannot lower the temperature below 100 since the flies suf-
fer in the chrysalid stage when the temperature becomes 100
or less. While these are thus far the only experiments on the
duration of life of higher organisms carried out with the neces-
sary scientific precaution, there are many casual observations
mentioned in the literature which suggest that lowering the
temperature prolongs the duration of life of lower animals
in general.
The body temperature of a normal human being is constant,
namely about 35.50 C. and this temperature remains the same
in the tropics and in the arctic regions. Human beings and
most mammals differ in this respect from insects whose tem-
perature is as a rule practically that of their surroundings. If
if were possible to reduce the temperature of human beings and
if the influence of temperature on the duration of life were the
same as that in the fruit fly, a reduction of our temperature
from 37.5 to about 160 would lengthen the duration of our life
to that of Methusaleh; and if we could keep the temperature of
our blood permanently at 7.50 C., our average life would (on
the same assumption) be lengthened from three score and ten
to about 27 times that length, i.e., to about nineteen hundred
years. Unfortunately our body does not tolerate any consider-
able lowering of its temperature and if it did, life at so low a
temperature would probably become very monotonous and un-
interesting since in all probability sensations of pleasure as
well as pain, of joy and of sadness, would be at a very low level.
The experiments on aseptic flies therefore lend support to
the idea that the duration of our life is the time required for
the completion of a chemical reaction or a series of chemical
reactions. If these reactions consist in the gradual accumula-
tion of harmful products in our body, or in the gradual destruc-
tion of substances required for a youthful condition, we under-
stand why senile decay and death are the natural result of life.

III
Unicellular organisms, like bacteria, algae or infusorians,
seem to be immortal. They reach a certain size, divide into
 NATURAL DEATH 583

two, each half growing again to full size and dividing again,
and so on. In this case we may say that it is practically the
same individual which continues to live in the successive gen-
erations. Small pieces of a cancerous tumor can be trans-
planted successfully to other individuals and these pieces grow
again to a large size. This process can also be repeated indefi-
nitely, and it is the same cancer cell which continues to live in
these successive transplantations, as it is the same bacterium
which continues to live in successive generations. In this way
it has been shown that cancers in mice may outlive many times
the natural life of a mouse, in fact they seem to live indefinitely.
Cancer cells may therefore be called immortal as was pointed
out by Leo Loeb many years ago.
It seems that this is true also for certain normal cells like
connective tissue cells. Carrel has isolated connective tissue
cells from the heart of a chick embryo and cultures of these cells
living on the extracts from chick embryos have been kept alive
now for seven years.
All this points to the idea that death is not inherent in the
individual cell, but is only the fate of more complicated organ-
isms in which different types of cells or tissues are dependent
upon each other. In this case it seems to happen that one or
certain types of cells produce a substance or substances which
gradually become harmful to a vital organ like the respiratory
center of the medulla, or that certain tissues consume or destroy
substances which are needed for the life of some vital organ.
The mischief of death of complex organisms may then be traced
to the activity of a black sheep in the society of tissues and
organs which constitute a complicated multicellular organism.

IV
While in human beings there is no sharp limit between youth
and maturity, in many insects and amphibians this limit is
marked by a sudden metamorphosis in the shape of their body.
The frog hatches from the egg as a tadpole without legs and
with a long tail. After a certain length of time legs begin to
grow, the tail disappears, the form of the head and mouth
change, the skin looks different, and the tadpole is transformed
into a frog. It is possible that some of the changes underlying
metamorphosis are due to changes in the circulation of the
blood. Gudernatsch made the remarkable discovery that this
metamorphosis, which in our climate usually occurs during the
third or fourth month of the life of the tadpole, can be brought
584 THE SCIENTIFIC MONTHLY

about at will even in the youngest tadpoles, by feeding them

with thyroid gland, no matter from which animal. By feeding
very young tadpoles with this substance, frogs not larger than a
fly could be produced. Allen added the observation that if a
young tadpole is deprived of its thyroid gland, it is unable
ever to become a frog; and that it remains a tadpole which can
reach, however, a long life and continue to grow beyond the
usual size of the tadpole. When, however, such superannu-
ated tadpoles are fed with thyroid they promptly undergo meta-
morphosis. These observations cleared up an old biological
puzzle. Salamanders also go through a metamorphosis which
is, however, less striking than that of the tadpole of a frog.
In the salamander the metamorphosis consists chiefly in the
throwing off of the gills, and in changes in skin and tail. In
Mexico a salamander occurs which through its whole life main-
tains its tadpole form, namely the axoloti. Attempts to induce
the axolotl to metamorphose failed until after Gudernatsch's
discovery an investigator fed the axolotl thyroid gland, and this
brought about metamorphosis. The thyroid gland stores the
traces of iodine taken up in our food and it seemed possible that
the iodine contained in the thyroid was the active principle
causing metamorphosis in tadpoles. This was confirmed by
Swingle who succeeded in inducing metamorphosis in tadpoles
by feeding them with traces of inorganic iodine. According to
our present knowledge, the duration of the tadpole stage seems
to be the time required to store the necessary amount of certain
compounds, one of which contains iodine.
Insects, like the fruit fly, hatch from the egg as maggots
which grow at the expense of the food they take up and which,
at a certain age, metamorphose into a chrysalid; and from this
chrysalid at a given time will rise the winged fly. Feeding of
thyroid to the maggots of the fruit fly will not accelerate their
metamorphosis, and we can not yet tell whether in this case
metamorphosis is due to the accumulation or formation of a
definite compound in the body, though this may well be the case.
The idea presented itself whetlher the duration of the larval or
maggot stage was not also determined by the temperature (pro-
vided the food supply was adequate). We measured, therefore,
the influence of temperature upon the duration of the larval
state in aseptic fruit flies-i.e., from the time the egg was laid
until the maggot was transformed into a chrysalid. The influ-
ence was practically identical with that of temperature on the
total duration of life. Thus the larval period lasted 5.8 days at
 NATURAL DEATH 585

250 C. and 17.8 days at 150 C., a ratio of about 1: 3. The total
duration of life of aseptic flies is 38.5 days at 250 and 123.9 days
at 150 C., also a ratio of about 1: 3. We are, therefore, justi-
fied in making the statement that the influence of temperature
upon the duration of the larval period or the youth of aseptic
flies is practically identical with the influence of temperature
on the total duration of life.
Experiments by Uhlenhuth on the influence of temperature
on metamorphosis in salamanders have shown that it is similar
to that observed in flies. Salamanders kept at 250 metamor-
phosed when they were 11 weeks old, while salamanders kept at
150, under otherwise identical conditions, metamorphosed when
they were 22 weeks old. All these data suggest the possibility
that the duration of life and the duration of the larval period
or of youth are in reality times required for the completion of
definite chemical reactions. The cessation of respiration lead-
ing to the termination of life and the alterations in circulation
leading to metamorphosis or termination of youth are critical
points; and it seems possible that these points are reached when
a certain toxic substance is formed in adequate quantity in the
body, or when a necessary substance is destroyed or sufficiently
diminished in quantity, or when both conditions are fulfilled.
We can prolong or shorten the period of youth in amphib-
ians not only by modifying the temperature but by withdraw-
ing or offering the specific substance which causes metamor-
phosis, namely iodine or thyroid material. There is no end to
the substances capable of hastening death. Shall we ever find
a substance which will prolong the duration of life? At pres-
ent we can neither deny nor affirm the possibility.