Table Of ContentPROTOMORPHOLOGY
THE PRINCIPLES OF
CELL AUTO-REGULATION
By
ROYAL LEE
and
WILLIAM A. HANSON
of the
Lee Foundation for Nutritional Research
WITH AN APPENDED ARTICLE ON
"CYTOTOXINES"
by
PROF. K. R. VICTOROV
Tintiryazew Agricultural Academy
Moscow, U.S.S.R.
'947
Published by
LEE FOUNDATION FOR NUTRITIONAL RESEARCH
MILWAUKEE 3, WISCONSIN
This book is sponsored by the Lee Foundation for Nutri-
tional Research, a non-profit institution chartered by the
State of Wisconsin, whose objectives are the investigation
and dissemination of facts relating to nutrition and asso-
ciated sciences. Therefore, it is freely offered as a con-
tribution to biological research without restrictions as to
reproduction if the source is properly acknowledged.
Lee Foundation for Nutritional Research
Printed in the United States of America
By the W. A. KRUEGER CO.
Milwaukee, Wisconsin, U.S.A.
Dedicated to the memory of
T. BRAILSFORD ROBERTSON, PH.D., SC.D.
and
FENTON B. TURCK, M.D.
whose keen minds and brilliant experiments have supplied
the germ from which the researches herein have been developed.
PREFACE
THAT OMNIFIC GENTLEMAN Leonardo da Vinci is reputed to have
generalized: "The supreme misfortune that can befall any man is
for him to embrace a theory mistaking it for a fact."
While engaged in compiling an exhaustive survey of the en-
docrine and nutritional factors affecting growth, we were struck
by the similarity of certain specialized growth factors reported
by various experimenters. Dr. Fenton B. Turck's quotation, "The
intrusion of something which the flesh engenders . . . not entering
from outside" (Imhotep, 4000 B.C.) has taken on a new and signifi-
cant meaning. These observations, as will be seen in the following
pages, have led to speculation on the basic problem of biology
and the presentation of a rationally integrated hypothesis for its
explanation.
In preparing the abstract of this hypothesis published herein, we
have constantly kept da Vinci's warning before us. We are fully
cognizant of the inevitable danger of errors in interpretation that
must, by the nature of our method, be inherent in this exposition.
We realize that there is scarcely a paragraph in this volume that
cannot be interpreted in many different ways other than that in
which we have.
We beg the indulgence of the reader, who will realize that the
work of corroboration and review cannot by its nature be estab-
lished on meticulous specialized experimentation. So long as one is
guided by Leonardo da Vinci's axiom and does not embrace the
theory in preference to the fact there is little danger to the scientific
method in its presentation. And if such an hypothesis is presented
freely and with the feeling that our reward will be measured by
the experimental work it stimulates, it can only be of benefit to
scientific progress. Ideas and hypotheses rise and fall on their merits.
It is only through critical experimental investigation that the truth
can be established. Such hypotheses, therefore, should not be de-
fended except by candid examination of factual evidence, for if
founded on misconceptions, no amount of persuasion can prop
them up, but if founded on basic truths, no amount of prejudice
can prevent their ultimate adoption.1
The outline contained herein has been prepared under the most
trying circumstances. Before and during the war both authors have
been forced to spend all but their sparse leisure time in activities di-
rectly related to the engineering of products necessary for national
defense. Our study and corroboration, therefore, is hardly begun.
We have thought it expedient, however, to publish that part of our
outline which has been thought through to a reasonable conclusion.
It is our hope that by doing so we may stimulate experimental
criticism of our hypothesis and thus add to the excellent work now
being conducted in this field. In a sense this outline can be con-
sidered a report of the "Lee Foundation for Nutritional Research"
on its planning of future activity in this field.
If there be any merit to the suggestions within these pages, little
credit can be claimed by the authors. We have been constantly ap-
palled by the insignificance of our difficulties in piecing together
this hypothesis in comparison with the inconceivable obstacles faced
by those men reviewed by us who have supplied us with the facts to
work with. The list of contributors of experimental evidence and
candid postulations, which comprise the true creators of this struc-
ture is substantially the entire bibliographic category of references.
We wish especially, however, to pay tribute to the three men
whose work has held the key to our hypothesis. Dr. Fenton B.
Turck, that practicing physician whose keen insight and monu-
mental curiosity led him to the investigation of the specificity of
ashed tissue extracts, deserves the honor of being possibly the first
to demonstrate some phenomena of Protomorphology and enlarge
upon its importance. Dr. T. Brailsford Robertson, the prolific
thinker, whose allelocatalyst theory, also expounded by others, is,
we believe, the cornerstone of the newer biology, deserves the
greatest credit for original thinking in many fields of biochemistry.
And Dr. Montrose T. Burrows whose investigations into the nature
1 Even while this volume is in process of publication we are gratified to notice
that recent experimental evidence seems favorable to one hypothesis we have ad-
vanced, that toxemia of pregnancy is caused by a disorder in the metabolism of
protomorphogen (thromboplastin).
See: Schneider, C. L., "The Active Principle cf Placental Toxin; Thrombo-
plastin . . ." Am. Jour, Physiol. 149:123-129. 1947.
vi
of "archusia" and "ergusia" have supplied, we believe, a basic
fundamental approach to the cancer problem, deserves commenda-
tion as one of the few original thinkers in American Medicine.
The list of scientific investigators who have contributed material
for our project is of international scope. We pay tribute to all those
whose work we have been honored to review herein.
We wish to acknowledge the financial assistance from those peo-
ple whose interest in sound nutrition has led them to contribute to
the support of the Lee Foundation for Nutritional Research. Their
aid has played no small part in making this publication possible. We
also wish to acknowledge the kindness of Dr. Otto Glaser of Am-
herst College reading the first four chapters and suggesting minor
changes although he cannot necessarily endorse our hypotheses
without more experimental substantiation. Our appreciation is
also extended to Dr. Charles Packard of the Woods Hole Biological
Laboratory, Woods Hole, Massachusetts, for his kindness in mak-
ing possible the use of their extensive library and reprint collection,
and to Dr. F. E. Chidester also at the Woods Hole Biological
Laboratory for his suggestions and generous assistance. Finally our
appreciation is extended to Miss Dorothy Tomsyck on the Research
Staff of the Lee Foundation for her work on bibliographic material
and preparation of the manuscript.
ROYAL LEE
WILLIAM A. HANSON
Milwaukee, Wisconsin
February, 1947
Vll
OUTLINE AND CONTENTS
CHAPTER i—BASIC BIOLOGICAL DETERMINANTS
PAGE
I. FUNDAMENTAL SCIENTIFIC CONCEPTS 3
Inorganic evolution 3
The form and characteristics of matter are a product
of its environment. The development of both inor-
ganic and organic forms is an evolutionary process
dependent upon the surrounding environmental in-
fluences.
Where "inorganic" evolution changes to "organic" ... 5
Organic evolution begins at that point where a special
"determinant" is necessary to maintain the integrity
of complex organic molecules.
II. BASIC BIOLOGICAL DETERMINANTS 8
Chromosomes, genes, cytomorphogens and proto-
morphogens are the basic biological determinants,
(the latter, being the basic determinant for the anti-
genically specific biological protein).
Antigenic "non-protein" substances n
Antigenic reactions involving ashed tissue substance.
Postulation that the antigenic protein is constructed
upon a stable spatial array of mineral linkages, the
fundamental characteristic of the protomorphogen
determinant.
Trace mineral elements and their importance in morphology 15
The suggestion is advanced that some of the impor-
tance of trace mineral elements in morphological de-
velopment is due to their use in the protomorphogen
molecule.
Determinants, viruses and nucleoproteins 24
Genie material and viruses have many points of sim-
ilarity. Assumption that protomorphogens are spe-
cific viruses answers some of the problems in this field
of research.
ix
CHAPTER 2—MORPHOGENS AS REGULATORS
OF CELL VITALITY
I. Experimental Basis of Their Influences in Cultures
PAGE
I. REVIEW OF ELEMENTARY PRINCIPLES 31
The dynamic state of living matter 31
The essential characteristic of living protein is a
dynamic state of anabolism and catabolism, the rate
of which is an index of vital activity.
Miscellaneous problems connected with morphogens. . . 32
Essential difference of protomorphogens and cyto-
morphogens; impossibility of strict definitions due to
the fact that these factors are dealt with in terms
of function rather than structure.
Chemical properties of morphogens 33
II. INTRODUCTION TO GROWTH INFLUENCES OF THE
MORPHOGENS 37
III. FACTORS INFLUENCING DIVISION RATE IN CULTURES OF
PROTOZOA 37
Relation of media volume 37
The vitality of infusoria bears a direct ratio to the re-
lationship between the number of cells and volume of
media.
Allelocatalyst theory 39
Cells secrete a product into the media; when the media
concentration of this product is low relative to the
protoplasmic concentration, it stimulates growth and
mitosis; when the contrary exists, the product inhibits
mitosis.
Stimulating effect of old media 41
When previously inhibited media is diluted into fresh
media, mitosis is stimulated.
Reciprocal ratio of intra-and extracellular auto-catalyst . . 45
Mitosis cannot begin until there is an optimum ratio
between these two which we term the "common de-
nominator" condition. Maximum culture population
is determined by the critical ratio between these two;
at this point mitosis is inhibited.
x
,-> PAGE
Conjugation and endomixis ^
Reproductive capacity of protozoa increased by these
processes. Necessity of considering the effect of these
phenomena on vitality of cells when choosing trans-
fers.
Review of allelocatalyst theory 52
A brief review of fundamental principles basic to the
allelocatalyst theory of control of mitosis.
Further notes on the allelocatalyst theory 53
A list of various experimental reports is presented re-
viewing the consensus of opinions on the allelocata-
lyst theory.
IV. FACTORS INFLUENCING DIVISION RATE IN TISSUE CULTURES . 55
Toxic concentrations of allelocatalyst in media .... 55
A factor secreted by cells accumulates in the media
inhibiting the division rate in cultures of metazoan
tissues.
Relation to media volume 57
Isolated tissue cells will not grow in a large volume
of media, a fact also discussed previously pertaining
to protozoa.
Stimulating influence of diluted allelocatalyst 58
Various investigations are reviewed reporting the
presence of a substance in the media of tissue cul-
tures, derived from the cells themselves, which stim-
ulates the mitotic rate in dilute amounts and inhibits
it when concentrated.
Universal nature of allelocatalyst phenomenon .... 59
The allelocatalytic theory applies to all animal cells
universally. The reciprocal relationship between pro-
toplasmic and media allelocatalyst concentration is the
basic universal influence over division rate and vitality
of the cell; it is primarily responsible for the degenera-
tive processes of old age.
V. THE ALLELOCATALYTIC GROWTH SUBSTANCE IS A
MORPHOGEN GROUP 62
The morphogens secreted by the cells as a product
of their metabolism are identified as the allelocatalytic
growth substance. A review of the theory is pre-
sented.
xi
