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THE VITAMINES



BY



CASIMIR FUNK

**
ASSOCIATE IN BIOLOGICAL CHEMISTRY

College of Physicians and Surgeons
New York City



Authorized Translation

from
Second German Edition

BY

HARRY E. DTJBIN

FORMERLY ASSISTANT IN RESEARCH MEDICINE
University of Pennsylvania
Philadelphia, Pa.



BALTIMORE

WILLIAMS & WILKINS COMPANY
1922



COPYRIGHT 1922
WILLIAMS & WILKINS COMPANY

Made in United States of America

The right of publication in English
is reserved



32NTAL DEPARTMENT



COMPOSED AND PRINTED AT THE

WAVERLY PRESS

BY THE WILLIAMS & WILKINS COMPANY

BALTIMORE, MD., U. S. A.



CONTENTS

Preface to the first edition 9

Preface to the second edition 11

Translator's note 13

Introduction 15

Historical survey 19

Introductory 35

PART I
THE VITAMINE REQUIREMENTS OF PLANTS AND ANIMALS

Chapter I. The role of the vitamines in the vegetable kingdom 49

Yeast 51

Bacteria 56

Fungi 64

Higher plants 65

Chapter II. The role of the vitamines in the animal kingdom 73

Life without bacteria 76

Protozoa 79

Metazoa 81

Growth of tissue in vitro 81

Insects 83

Fish 85

Amphibia 85

Birds 87

Chickens normal nutrition ; chicken beriberi 87

Pigeons beriberi 95

Pathological anatomy and chemical pathology of beriberi in birds. 103

Mammals 109

Rats 110

Mice 125

Guinea pigs 127

Rabbits 134

Cats 135

Lions 136

Dogs 136

Domestic animals sheep, goats, reindeer, pigs, horses, cows,

oxen, (stijfziekte, lamziekte, pica) 140

Monkeys 153

Man.. . 155



4 CONTENTS

PART II
CHEMISTKY, PHYSIOLOGY AND PHAEMACOLOGY OF THE VITAMINES

Chapter I. The antiberiberi vitamine Vitamine B 163

Chemical investigation of rice polishings 167

Chemical investigation of yeast 177

Other sources of supply 192

Synthetic experiments 193

Stability of the antiberiberi vitamine against heat and chemical and

physical agents 194

Demonstration and estimation of antiberiberi vitamine 195

The possible identity of vitamine B with the substance stimulating

the growth of animals and of yeast 203

Specificity of antiberiberi vitamine 205

Physiology and pharmacology of antiberiberi vitamine 207

The influence of the dietary composition on the vitamine requirement . 210

Chapter II. The antirachitic vitamine Vitamine A 218

Chemistry of cod liver oil 218

Chemistry of vitamine A in butter and other sources 220

Nature of vitamine A 222

Demonstration of vitamine A 225

Chapter III. Relationship of the antiberiberi and antirachitic vitamines

to lipoids 228

Chapter IV. The antiscorbutic vitamine Vitamine C 231

The chemistry and the nature of vitamine C 231

Chapter V. Vitamine content of various foodstuffs in the natural and

prepared condition 236

Influence of heating and cooking on the vitamine content 238

Vitamine content of the cooking water 241

Influence of drying 241

Influence of canning 242

Influence of ageing and storing 243

Cereals 244

Rice 248

Barley 248

Oats 249

Wheat 249

Maize 250

Potatoes 255

Milk 256

Demonstration of vitamines in milk 256

Influence of food on the vitamine content and composition of milk 257

Vitamine content of milk 258

Influence of heat on the vitamine content of milk 259

Influence of drying and evaporation 260

Nutritive value of milk. . 261



CONTENTS 5

Meat 262

Table showing the vitamine content of the most frequently used
foodstuffs 263

PART III

THE HUMAN AVITAMINOSES CONDITIONS IN WHICH THE VITAMINES

PLAY A R6LE

Chapter I. Beriberi 275

Mode of occurrence of and diets leading to beriberi 280

Symptomatology and types of beriberi 282

The sensory, motor form 283

The dry, atrophic form ' 287

The wet, atrophic form. 287

Epidemic dropsy 288

The pernicious, acute form 289

Infantile beriberi 290

Pathology 291

General 291

. Blood . 293

Cerebrospinal fluid 293

Urine 293

Therapy 293

General 293

Infantile 294

Ship beriberi 294

Relationship between beriberi and scurvy 295

Chapter II. Scurvy 297

Mode of development 300

Symptomatology and progress of scurvy 303

Infantile scurvy 306

Diagnosis 307

Hematology 308

Metabolism experiments 308

Pathology 308

Barlow's disease 309

Therapy 311

Chapter III. Rickets 312

Occurrence 313

Symptomatology and diagnosis 315

Pathological anatomy and chemical pathology of rickets 315

Metabolism 317

Therapy and therapeutic effect on metabolism 220

Etiology 323

Vitamine etiology of rickets 324



6 CONTENTS

Osteomalacia 329

Symptoms 330

Anatomy 330

Metabolism 331

Therapy 331

Etiology 331

Chapter IV. Some nutritional disturbances in children tetany, carbohy-
drate dystrophy (Mehlnahrschaden), atrophy 332

Tetany (Spasmophilia) 332

Etiology 332

Symptoms 333

Therapy 334

Carbohydrate dystrophy (Mehlnahrschaden) 335

Etiology 336

Atrophy 336

Other nutritive disturbances of children 337

Chapter V. Nutrition in man An introduction to the study of pellagra

and hunger edema 340

Chapter VI. Pellagra 351

Geographical distribution 351

Progress of pellagra ". . . 352

Acute, malignant form 354

Light, sub-chronic form 354

Severe, cachetic sub-chronic form 354

Chronic form 354

Symptomatology and pathology 355

Gastro-intestinal tract 355

Skin 357

Nervous system 357

Circulatory system 359

Bones 360

Sexual organs 360

Other organs 361

Chemical pathology 361

Metabolism ...... 362

Prognosis 362

The relationship of pellagra to the accepted avitaminoses beriberi

and scurvy 362

Mode of development of pellagra 363

Therapy 366

Etiology 366

Chapter VII. Sprue 369

Symptomatology 369

Pathological anatomy 370

Therapy 370

Pathogenesis 371



CONTENTS 7

Chapter VIII. Hunger edema 372

Symptomatology and mode of development 373

Pathology 374

Metabolism 375

Therapy S75

Etiology 376

Chapter IX. Pathological conditions in which the lack of vitamines may

be suspected 378

Kallak 378

Trench Sickness 378

Intestinal stasis, etc 379

Sterility 379

Hemeralopia 379

Exophthalmic goitre (Graves' Disease), 380

Significance of vitamines in infections 380

Ophthalmia 381

Nature of the disease 382

Tuberculosis 384

Leprosy 385

Pneumonia 385

Chapter X. Influence of nutrition (vitamines) on the action of some

poisons and upon pathological conditions of non-infectious origin . . . 386

Anemia, etc 386

Diabetes 387

Cancer 388

Development of teeth 391

Calculi 393

General literature on the subject of the vitamines 395

Literature to the text 399

Index to Sectional Divisions of the Literature 476

Author index 477

Subject index 491



PREFACE TO THE FIRST EDITION

This initial attempt at a classification of our knowledge on vita-
mines and avitaminoses contains, besides a number of facts, the per-
sonal conceptions of the author, new questions, ideas and lines of
research. Much of the material is fragmentary while some of it is
purely hypothetical. This small book is to be regarded as the first
step in a new direction in the field of physiology and pathology.
Many facts are still lacking in this field of work so that hypotheses
must naturally fill the gaps. Even if the structure is skeleton-like,
at least the fundamentals are well established.

At this point, I want to thank Dr. F*aser, Dr. Stanton, Prol
Hoist, Dr. Mott, Dr. Roberts, Dr. Standwith and Dr. Zeller, and the
London Society of Tropical Medicine, for the permission to reproduce
illustrations. I am thankful also to Dr. Macauley of Cape Town for
having called my attention to a South African cattle disease. In
particular, do I wish to express my deepest gratitude to my Father,
Dr. J. Funk, for his unvaried and tireless assistance.

I would appreciate it greatly if the investigators who are conducting
research on problems discussed in this book would be kind enough
to send me reprints of their work which, at times, is available only
with great difficulty.

THE AUTHOR,

Cancer Hospital Research Institute,
Brompton, London, S. W.

October, 1913.



PREFACE TO THE SECOND EDITION

This edition, totally revised and almost completely re-written,
appears seven years after the first edition, deferred because of the
World War. In the interim, we have received many communications
from our colleagues informing us that our effort had provided them
with a welcome stimulus to their work. We have watched the great
development of this field of research since the appearance of The
Vitamines and it is a source of great pleasure that our work has also
contributed to this progress. The views expressed at the time have
been tested, for the most part, and found correct. While the first
edition was published at a time when great differences of opinion
prevailed, our desire then being to take cognizance of all of them, we
feel justified now in reviewing only those investigations, the view-
point of which is not too far removed from ours. In this way, it
has been possible to make the book more comprehensive. The
subject of vitamines, already beyond the stage of hypothesis, is based
on a firm foundation and has received universal recognition. In
spite of this, however, we are well aware that great gaps exist in our
knowledge, so that we can not regard the chapter as closed.

These gaps may be explained by the fact that the field of vitamine
research gave many investigators the opportunity of making a name
for themselves with rather superficial work. Only seldom did they
seriously endeavor to get at the basis of the phenomena observed.
To permit of progress in the subject of vitamines, it would be very
desirable that at least some of the workers should abandon the beaten
path of exclusive animal experiments and break a fresh trail leading
towards the chemistry, physiology and pharmacology of the vitam-
ines, as well as the anatomical pathology of the avitaminoses.

For help in the preparation of this edition, we are indebted to
many of our colleagues; we wish also to express our thanks to the
Medical Research Committee (London) and to Dr. Alfred F. Hess
(New York) for permission to reproduce a number of illustrations.
In addition, we wish to thank those whose permission it was impos-
sible to obtain because of uncontrollable circumstances. We are
especially grateful to Dr. Richard Hamburger, First Assistant at the
Pediatric Clinic, Berlin, who took it upon himself to correct and
critically review the proofs.

11



12 PREFACE TO SECOND EDITION

In particular, however, we take pleasure in recording our apprecia-
tion of the assistance extended by the Hon. Herman A. Metz (New
York) who, although a layman in this field of work, understood its
significance and gave us the opportunity, after an enforced interrup-
tion of many years, of resuming the experimental work in the
"Research Laboratory of H. A. Metz."

This book will be of interest not only to nutrition investigators
and childrens' specialists, but to every physician who comes into
touch with questions of the physiology of nutrition. It treats many
problems which are closely allied to other lines of research and will
be of value to plant physiologists, bacteriologists and animal breeders.

CASIMIR FUNK.

College of Physicians and Surgeons,

Columbia University,

New York City.

December, 1921.



TRANSLATOR'S NOTE

The translator has been associated with the author for three years
in experimental vitamine research, and it is a pleasure to record at
this point the spirit which animates him in his work and his earnest
desire to see real progress made towards the solution of the many
problems of nutrition. It was this which prompted the preparation
of the present edition, intended rather as a stimulus to thought and
further research than as an elaboration of technicalities. Inasmuch
as the author has had the opportunity of reading the manuscript
before it went to press, the reader may be sure that the sense of the
book has been accurately preserved.

In conclusion, the undersigned wishes to extend his thanks to the
Hon. Herman A. Metz for the many facilities provided in the prepara-
tion of this book.

HARRY E. DUBIN.

Research Laboratory of H. A. Metz,
New York City.

December, 1921.



13









INTRODUCTION

The first edition of this book, drafted seven years ago, was intended
to serve the purpose of directing the attention of the medical and
chemical professions to this new and attractive field of investigation.
The findings upon which we based our views in 1913 appeared indeed
to be far from indisputable but time has shown the comparative
accuracy of our conception. Since then, we have made it a point
to note any work that might have some bearing upon the question
of the vitamines, and have now undertaken to point out what may
be regarded as erroneous and what may be looked upon as correct,
in the light of the present status of the subject.

Our original classification included beriberi, scurvy and Barlow's
disease as true avitaminoses, while pellagra, sprue, rickets, and some
metabolic diseases of animals, were held to be hypothetical avitam-
inoses. At present, beriberi, scurvy and Barlow's disease are uni-
versally accepted as true avitaminoses, while rickets is quite generally
acknowledged as such. The etiology of pellagra and sprue, on the
other hand, has not yet been definitely established. Regarding
pellagra, which we shall discuss later, the dietetic hypothesis is at
present in the foreground.

As for the chemistry of the vitamines, an examination of the
literature reveals little progress in this direction. To be sure, one
must bear in mind that the outbreak of 1 the war was not particularly
conducive to the long and tedious research that is necessary, if this
phase of the subject is to be cleared up. From tune to time, word
comes from this or that laboratory to the effect that the puzzle has
been solved that progress has been made even towards the synthesis
of the vitamines but after much patient waiting, nothing more is
heard of the discovery. However, since a large part of the experi-
mental work is being carried on in many industrial research labora-
tories, it is quite possible that definite important progress has been
made, of which reports have not yet been published.

Incidentally, the war has given added impetus to vitamine research
in another direction. The vitamines have now become of great
importance from the point of view not only of pure science and medi-
cine, but also of political economy much greater than could have

15



16 THE VITAMINES

been foreseen when the first edition of this book appeared. The
war, first of all, prevented the normal interchange of foodstuffs
among the various countries. Subsequently, this was followed by a
disturbance in the entire mode of living, due to the necessity of
making war, the utilization of farm labor for other purposes, and the
lack of means of transportation. Although, as this is being written,
more than two years have elapsed since the end of the war, conditions
have become worse instead of better, according to available reports.
Similarly, notwithstanding the national rationing of food both
during and after the war, the people have suffered because of the
mistakes made during the war. In the face of higher prices, general
unrest and unwillingness to settle down again to some productive
work, the abnormal conditions already mentioned will likely prevail
for several years to come. It is not our purpose to suggest that
knowledge of the vitamines will solve the present difficulties. Still,
we shall call attention to facts and principles which, at present, are
of universal interest principles which may contribute to the allevia-
tion of the wretchedness of stricken Europe.

Considering more closely the dietaries of farmers and of the rural
populations in various parts of the world, it is easy to see that no
knowledge of vitamines is necessary to keep those people in good
health. From generation to generation, their nutrition has been
regulated according to the climate, the economic situation, and the
exigencies of the work performed. Of course, in some oriental
countries, where conditions are not so well known to us, instinct some-
times does not choose the correct food and hence the prevalence of
beriberi. All in all, we see that the white races have a wholesome
knowledge of their food requirements, which is only natural. In
certain provinces, before the war, it was possible to see examples of
particularly monotonous and simple dietaries accompanied, on the
whole, by no pathological conditions. We may be sure, however,
that since these same peoples apparently subsisted on a practically
unchanging diet for hundreds of years, they would most certainly not
have survived if their choice of diet had been anything but correct.

When the usual equilibrium is disturbed by extraneous conditions
such as war, a financial crisis or a catastrophe, then the practical
knowledge of centuries suddenly becomes useless to the people, and
they are obliged to seek some other basis of existence. Untold
hardships are endured till this is accomplished, the population func-



INTRODUCTION 17

tioning similar to experimental animals, used to establish the value
of new foodstuffs. Here, at least, there is the added advantage of
successfully applying the various principles of nutrition and sharply
terminating the unnecessarily protracted period. In this connection,
it is not impossible to make immediate use of the enormous amount
of information obtained on the subject, both before and during the
war, especially by the United States and England. During the past
few years, virtually all foodstuffs have been tested as to their nutritive
value and their vitamine content. Although most of the data secured
are the results of animal experiments, they are, with a few reserva-
tions, directly applicable to man especially as it has been demon-
strated that there are no vital differences between the findings
obtained with man and those with animals.

In general, it may be said that during the war, and after, there
was a disarrangement of the nutritional elements resulting in a
decreased consumption of protein and fat and a greater intake of
carbohydrate, together with a diminution of vitamines. It should
be noted here that the more important dietary constituents, in com-
parison with the physiologically inferior ones, have increased greatly
in price, so that there is this danger to contend with in addition to
the element of scarcity. Now, when a well-planned animal experi-
ment is undertaken, all factors are controlled as far as possible except
that one whose influence upon the organism is being determined.
Quite another state of affairs confronts us in the case of nutrition
investigations on man, where conditions arise which are only rarely
met with in animal experiments. If there is a lack of one constituent,
then it is almost certain that the entire choice of diet is not correct.
For example, if the protein content of the diet is too low, it is at the
same time apparent that the carbohydrates are present in excess,
that the vitamine content is diminished, and that the inorganic
elements are inadequately grouped. It is easily possible that right
at this point is where we must search for an explanation of the
pathologically occurring avitaminoses, the etiology of which it is so
difficult to establish. If in such a case as mentioned above, the
missing factor in the diet is supplied, good results do not follow, for the
reason that still other factors have not been taken into consideration.

Under certain circumstances, a seemingly well chosen diet may
prove to be inadequate, particularly when special demands are made
upon the individual, such as hard work, growth, birth, and nursing.



18 THE VITAMINES

All these factors must be taken into account when commenting upon
the pathological conditions which are of exceptional interest to us.
These are chiefly the conditions which give us an insight into the
causes, which are so difficult to determine in hunger edema and
pellagra. Even a well informed physician may easily be led astray.
He questions his patients about their diet, whereupon they enumerate
a long list of foodstuffs, from which apparently nothing has been
omitted. Immediately, his attention will be directed to obvious
things, such as mode of living, nature of work performed, and method
of preparing and cooking the food everything which may be etio-
logically important and may help him solve his problem.

Despite the fact that a number of ideas originated by us are
credited to others, it is a source of pleasure to witness the great
progress that has been made in vitamine research. In our opinion,
the name "Vitamine", proposed by us in 1912, contributed in no
small measure to the dissemination of these ideas. The word,
"Vitamine", served as a catch word which meant something even to the
uninitiated, and it was not by mere accident that just at that time,
research developed so markedly in this direction.

Our view as to the fortunate choice of this name is strengthened, on
the one hand, because it has become popular (and a badly chosen
catchword, like a folksong without feeling, can never become pop-
ular), and on the other, because of the untiring efforts of other workers
to introduce a varied nomenclature, for example, "accessory food
factors, food hormones, water-soluble B and fat-soluble A, nutramine,
and auximone" (for plants). Some of these designations are cer-
tainly not better, while others are much worse than " Vitamine."



HISTORICAL SURVEY

In spite of the fact that the knowledge of the vitamines taken as
a whole is not older than ten years, and although until lately the
idea was prevalent that for the complete nutrition of an animal
organism only proteins, fats, carbohydrates, salts and water were
necessary, there is nevertheless, in the older literature, no lack of
statements which of themselves should have given rise to an eager
search for additional dietary components essential to life. The
progress which has already been made by research in vitamines
removes all doubt as to the actual existence of such substances, and
every year brings forth new findings which enhance the importance
of the vitamines to life.

The scientific research leading to the conception of the vitamines
proceeded through many intermediate stages, which we shall shortly
describe. A great stimulus to the development of the modern science
of nutrition was furnished by the investigations into the chemistry
of the proteins which we owe, above all, to the classical work of
Emil Fischer and Kossel. These investigations not only contributed
to the knowledge of the composition of the proteins, but also gave rise
to the study of the relationship between the individual dietary con-
stituents. They demonstrated particularly, that the various proteins
exhibited, qualitatively as well as quantitatively, a varied composi-
tion, and that naturally occurring proteins have not the same physi-
ological value. Without going into details, which may be found in
any text-book, we shall take up only those facts bearing upon the
study of the vitamines. It has been shown by many investigations
that certain amino acids, such as tyrosine, tryptophane, arginine and
lysine, are more or less indispensable to the animal organism. This
question is not yet completely settled, but we know, however, that
some proteins, for example, zein (which is lacking in tryptophane),
or gelatine (which lacks several important amino acids), are not
sufficient for normal maintenance and growth. Latest developments
also indicate that an animal will utilize a diet containing animal
proteins, better than one made up of plant proteins. This conception
is based preeminently upon the supposition that animal proteins
have a composition more nearly related to body protein than do plant

19



20 THE VIT AMINES

proteins. That is to imply that the animal organism needs a smaller
amount of animal protein to maintain its nitrogen balance. This
view was utilized by Thomas (1) to group the various proteins of
animal and plant origin according to their biological value. All
these questions have exerted their influence upon the development
of the study of the vitamines, and are even now closely related to
many of our problems to which we shall call attention later.

Another matter that is of interest, is the extent of the ability of
the animal body to synthesize many of the substances necessary for
its existence. The peculiar deficiency symptoms, of which we speak
in this book, have often been attributed to the apparent inability of
animals to synthesize some of the body constituents. The sub-



Online LibraryCasimir FunkThe vitamines → online text (page 1 of 44)