title: author: publisher: isbn10 | asin: print isbn13: ebook isbn13: language: subject publication date: lcc: ddc: subject: Biochemical Individuality : The Basis for the Genetotrophic Concept [1998 Ed.] Williams, Roger John NTC Contemporary 0879838930 9780879838935 9780071405027 English Biochemical variation, Human genetics Variation, Nutrition Genetic aspects 1998 QH345.W49 1998eb 612/.015 Biochemical variation, Human genetics Variation, Nutrition Genetic aspects Page iii Biochemical Individuality The Basis for the Genetotrophic Concept Roger J Williams, Ph.D Consultant and Co-Founder, Clayton Foundation Biochemical Institute The University of Texas at Austin With a New Introduction by Jeffrey S Bland, Ph.D KEATS PUBLISHING NEW CANAAN, CONNECTICUT Page iv Biochemical Individuality is intended solely for informational and educational purposes, and not as medical advice Please consult a medical or health professional if you have questions about your health BIOCHEMICAL INDIVIDUALITY © 1956 Roger J Williams Copyright renewed 1984 Roger J Williams © 1998 The University of Texas at Austin By gift of Mrs Roger J Williams All rights reserved No part of this book may be reproduced in any form without the written consent of the publisher ISBN: 0-87983-893-0 Library of Congress Cataloging-in-Publication Data Williams, Roger John, 1893Biochemical individuality : the basis for the genetotrophic concept / Roger J Williams : with a new introduction by Jeffrey Bland.2nd ed p cm Previously published: 1956 Includes bibliographical references and index ISBN 0-87983-893-0 Biochemical variation Human geneticsVariation NutritionGenetic aspects I Title QH345.W49 1998 612'.015dc21 98-5055CIP Publication History John Wiley & Sons, Inc., hardcover (1956) and softcover (1963) The University of Texas Press, softcover 1969 (seven printings; out of print 1988) Translations published in Russian (1960), Italian (1964) and Polish languages (1969) Printed in the United States of America Keats Publishing, Inc 27 Pine Street (Box 876) New Canaan, Connecticut 06840-0876 Full catalog and ordering information: www.keats.com Page v Contents Introduction to 1998 Edition vii Foreword xiii Preface xv I Biochemical Variation: Its Significance in Biology and Medicine II Genetic Basis of Biochemical Individuality III Anatomical VariationsSignificance 19 IV Individuality in Composition 51 V Individual Enzymic Patterns 77 VI Endocrine Activities 89 II Excretion Patterns 109 VIII Pharmacological Manifestations 119 IX Miscellaneous Evidences of Individuality 135 X Individuality in Nutrition 153 XI The Genetotrophic Approach 189 XII Implications for the Biological Sciences 202 XIII Implications for Medical and Dental Research 209 XIV Implications for Advance in Psychiatry Afterword to 1998 Edition 225 In Memoriam: Roger John Williams, 18931988 248 Index 257 240 Page vii Introduction to 1998 Edition What are the characteristics of a "classic book"? Is it the timelessness of the message? The insight which spurred the development of a field? The contribution to a new way of thinking that significantly improved the state of society? Or the ability to see the "obvious" in a way that had never been seen before and so well communicated? The book Biochemical Individuality, authored by the late worldrenowned biochemist Roger Williams, Ph.D., first published in 1956, fulfills all of these characteristics It is a book that should be on the bookshelf of all students and practitioners of modern molecular medicine It is with great admiration and respect that I have the privilege of writing the introduction to the republication of this timeless work Molecular medicine was a term used by two-time Nobel laureate in chemistry and peace Linus Pauling, Ph.D., in his landmark article on the mechanism of production of sickle cell anemia published in 1949.1 It defined a new perspective on the origin of disease based upon the recognition that specific mutations of the genes can create an altered "molecular environment" and therefore the modified physiological function associated with specific diseases Dr Williams contributed to the evolution of the understanding of the molecular origin of disease with the development of the concept of biochemical individuality He described anatomical and physiolog- Page viii ical variations among people and how they related to their individual responses to the environment He was the first to gain recognition for the term "biochemical individuality" and how this related to differing nutritional needs for optimal function among different people He pointed out that even identical twins could be different in their needs for optimal function based upon the fact that they developed in different environments in utero Although identical twins share the same genes, their differing nutrition and developmental environments can result in different expression of the genes as they grow older In the 1980s the field of biochemical individuality became fashionable within science as a consequence of the progress made in understanding the molecular biology of the gene The Human Genome project represented a major international commitment of scientists to understand the genetic code of life by sequencing the human chromosomes As this story has unfolded from laboratories around the world, its implications have been revolutionary in terms of how medicine views genes and their function The genetic structure is no longer seen as "rigid" as previously considered Rather, as Bishop and Waldholz pointed out in their book Genome, "aberrant genes not, in and of themselves, cause disease By and large their impact on an individual's health is minimal until the person is plunged into a harmful environment The list of common diseases which has its roots in this genetic soil is growing almost daily How many human ills will be added to the list is unknown, although some contend that almost every disorder compromising a full and healthy four score and ten years of life can be traced in one way or another to this genetic variability" (Simon and Schuster, New York, 1990) The first major breakthrough that resulted in this revolutionary change in thinking about the origin of disease was the recognition that we are much more different biochemically than was previously acknowledged.2 Dr Williams in Biochemical Individuality pioneered this revolution in thinking forty years ago Genetic polymorphism is the term which has emerged in the past decade to describe this variation in function surrounding a specific genetic trait The second major breakthrough in thinking made by Dr Williams is the recognition that nutritional status can influence the expression of genetic characteristics.3 Once again Dr Williams foresaw this Page ix important concept in Biochemical Individuality and set in motion research and discoveries over the past four decades that have transformed medicine It is now well recognized that our genotype gets transformed into our phenotype as a consequence of nutritional, lifestyle and environmental factors which are important in determining our health patterns In 1976 Dr Williams and his colleague Donald R Davis, Ph.D., co-authored a paper entitled "Potentially useful criteria for judging nutritional adequacy" in which they provided observations about how nutritional status can influence the functional expression of the genes They pointed out that phenotypic characteristics such as voluntary consumption of food, sleeping time after anesthesia, weight gains after surgery, healing time after surgery, hair growth after clipping, voluntary sugar consumption and recovery time after poisoning could all be influenced by nutritional influence on gene expression.4 The concept of biochemical individuality has become part of most contemporary clinical and experimental medical and nutritional research People are now known to fit into personally unique biochemical profiles based upon their own genetic structure, nutrition and environment.5 There is no such thing as a truly "normal" individualmeaning average We are all biochemically unique and need to be dealt with as such The Recommended Dietary Allowances (RDAs) which were developed by the Food and Nutrition Board of the National Research Council to establish the nutritional needs of "practically all healthy people" were not based upon the more recent information concerning the range of biochemical individuality among individuals The RDAs that describe "normal" nutritional needs have questionable relevancy to the concept of optimal nutrition based upon individual needs The contributions of Dr Williams have opened the door for personally tailored nutritional and medical interventions that take biochemical individuality into account Some of the world's foremost nutrition and medical researchers are now actively involved in developing a better understanding of the field which Dr Williams pioneered Rucker and Tinker from the University of California at Davis, Department of Nutrition, have described the role of nutrition in gene expression and its relationship to biochemical individuality as "a fertile field for the application of molecular biology."6 It is now well known that significant biochemi- Page x cal diversity occurs in such physiological functions as the ability of the individual to detoxify both exogenous and endogenous substances, the control of blood cholesterol, the metabolism of the potentially harmful amino acid homocysteine, and the response of certain cancer genes to the diet and environment These are all examples of how nutritional status can influence disease patterns based upon biochemical individuality Dr Williams coined the term "genetotrophic disease" to describe diseases which resulted from genetically determined nutritional or metabolic needs not being met by the individual and which resulted in poor gene expression Motulsky has recently argued that many of the common degenerative diseases are the result of the imbalance of nutritional intake with genetically determined needs for good health.7 The genetic concept with which most nutrition and medical researchers grew up intellectually before the contribution of Dr Williams was that of Gregor Mendel His concept of dominant and recessive genetic characteristics gave us the belief that our characteristics are "locked in stone" when the sperm meets the egg Dr Williams opened the eyes of the research communities that the expression of genes and therefore phenotypic function was modifiable through altered diet and nutritional status He pointed out that human biochemical variation in function was much greater than nutrition and medicine recognized prior to his publications.8 Simopoulos has stated that "of all the recent scientific advances contributing to our understanding of the role of nutrition in disease prevention and the variability in human nutrient needs, the recognition of genetic variation as a contributing factor must rank among the highest."9 Dr Williams made this complicated story easy to understand and compelling to health scientists and the general public alike His clarity of thought and language helped open up this field which had been dominated by Mendelian thinking for nearly one hundred years before the publication of Biochemical Individuality In one of his lectures at which I was in attendance he responded to an inquiry as to why the RDAs were not sufficient to define a person's nutritional needs with the simple insight, "Nutrition is for real people Statistical humans are of little interest." It is very timely that Biochemical Individuality is being reprinted Page xi over forty years after its initial publication, and that it is even more timely today than at the time of its original publication By all definitions Biochemical Individuality fulfills the definition of "a classic" and should have an honored place among the principal reference books of anyone interested in health and nutrition JEFFREY S BLAND, Ph.D HEALTHCOMM INTERNATIONAL, INC GIG HARBOR, WA References Pauling L, Itano HA Sickle cell anemia: a molecular disease Science 1949; 110:543548 Motulsky AG The 1985 Nobel Prize in physiology and medicine Science 1986; 231:126127 Holtzman NA Genetic variation in nutritional requirements and susceptibility to disease: policy implications Am J Clin Nutrition 1988; 48:15101516 Davis DR, Williams RJ Potentially useful criteria for judging nutritional adequacy Am J Clin Nutrition 1976; 29:710715 Robertson EA, Young DS Biochemical individuality and the recognition of personal profiles with a computer Clin Chemistry 1980; 26:3036 Rucker R, Tinker D The role of nutrition in gene expression: A fertile field for the application of molecular biology J Nutr 1986; 116:177189 Motulsky A Nutrition and genetic susceptibility to common diseases Am J Clin Nutrition 1992; 55:1244S1245S Motulsky A Human genetic variation and nutrition Am J Clin Nutrition 1987; 45:11081113 Simopoulos AP Genetic variation and nutrition Nutrition Today 1995; 30:157167 Page 262 Hoch, Paul H., 229 Hollinshead, W Henry, 32 Holmes, Julia Outhouse, 218 Holmes, Oliver Wendell, 191 Holt, L Emmett, 171, 172 Houlahan, Mary B., 10-11 Houssay, B A., et al., 95 humanics, 253 Huxley, Julian, hypertension, 216, 235, 241 hyperuricemia, 213-214 I immunity, 149-150 ''Inborn Errors of Metabolism," 109 inbred animals, 15, 112, 114f disease susceptibility variation, 218-219 nutritional experiments and, 183, 198 pharmacological testing and, 120 individuality, biochemical, 1-7 See also deviates; normal applied science and, 202-204, 206-207 brain anatomy, 226-227 environment vs inheritance, 8-9, 16 exceptional, 123, 197 genetic basis of, 8-18 medical application of, 222-223 metabolic peculiarity and, 209-213 nutrition and, 178-180 quantifying, 204-205 research focus on, insomnia, 235 insulin, 94-97 intelligence, 161-162 International Academy of Preventive Medicine, 254 intestines flora in, 149, 179 variation in, 25-26 intoxication, pathological, 122 iodine, 56, 157 J Javert, Carl T., 168 Jetter, W W., 121 K Kallmann, Franz J., 231, 235 Kalter, Harold, 127 Kerr, Standley E., 54 Kinsey, Alfred C., et al., 98, 105, 231 Kleitman, N., 138 Klemperer, Friedrich, 213 Kraines, Samuel Henry, 230 Krantz, John C., Jr., 119, 131 L Laboratory of Animal Nutrition, Alabama Polytechnic Institute, 178 laryngeal nerves, 45 Lashley, K S., 48-49 Lewis, Paul A., 193 Libman, Emanuel, 139 Liddell, Howard S., 230 Light, R F., 170 lipase in serum, 81 liver cirrhosis of, 216 variations in, 26, 28f, 29, 29f Loeb, Leo, 150 Lowry, Oliver H., 170 Lucas, C C., 80 Lurie, Max B., 193 lysergic acid, 228 M Mack, Pauline Beery, 70 Macy, Icie G., 115, 155, 182 "Mad" hatters, 228 Malamud, William, 230 malformations, 216 Man, Evelyn B., 59 Page 263 Mann, Joseph D., et al., 80 mannose, taste of, 145 ''Man's Understanding of His Own Nature" seminar, 200 Mardones, J et al., 182 Maresh, Marion M heart development study, 30 paranasal sinus study, 37 marijuana, 228 McLester, James S., 167-168 Mead Johnson and Company, 162-163 medicine, individualized, 222-223 Meister, Alton, 78, 82 mercuric chloride, variation in response to, 123 mescaline, 228 metabolism, 203 brain, 227-228 gout and, 213-214 significant peculiarities in, 209-213, 216, 217, 219 methyl thiouracil, 126 microbiology, 206 milk composition, 68-69 production, 103 minerals, variation in levels of, Mitchell, H M., 155 Mitchell, Herschel K., 10-11, 12 monkeys insulin and, 96 niacin and, 174 thyroid hormone and, 92 morphine, 125, 228, 252 morphology, 8-9, 12, 19 multiple sclerosis, 216 Murlin, John R., et al., 161 muscular dystrophy, 216 musculature fat, bone, layers of, 43-44, 44t variations, 40-44 mutation, 9, 10-11 myasthenia gravis, 216 N Nagle, John M., 121 Najjar, Victor A., 171, 172 et al., 173 National Cholesterol Education Program, 242 Nelson, Erwin E., 128 Nelson, Marjorie M., et al., 176 nephrosis, 216 nerve action, 205 facial, 46f pyramidal tracts, 45 quantitative research and, 205-206 neural tube defects, 243 neuroanatomy, variations in, 45-49 Neurospora, mutations in, 9-11 niacin, 174 deficiency, 232 nicotine, response to, 124 Nims, Leslie M., 142 noradrenaline, 126-127 normal abnormal vs., 2-3, 195 exceptional individuals, 197 man, 6, 195-196, 212, 241, 242 ranges, 2-4, 61-64, 99-100 social welfare and, 253 study sample size and, 168-169 nutrition, 153-184 See also deficiencies, nutritional; specific vitamins alcoholism and, 233-235 amino acids, 160-162, 199 calcium, 155-157 dental caries and, 220 excretion patterns and, 110-111 genetic weakness and, 13 genetotrophic principle and, 190, 191, 194-197 Page 264 individual needs and, 178-180, 241 intelligence and, 161-162 interrelations, genetotrophic principle and, 198-199 magnesium, 157 mental disease and, 232-236 metabolism and, 136-137, 136t phosphates, 157 potassium needs, 153-154, 199 self-selection in, 180-184 sodium, 154, 199 starvation, 232 success and failure of, 192-193 trace elements, 157-160 unrecognized factors, 184 vitamins, 162-178, 198-200, 204-205, 253 Nutrition, Division of, Department of National Health and Welfare of Canada, 173 O organ weights studies, 19-21 Orientals, calcium supply of, 156-157 Osler, William, 2, 193 Osteogenesis imperfecta, 69-70 osteoporosis, 243 Osterberg, Arnold E., et al., 65-67 ova, number of, 97 ovaries, 97, 99 oxygen deprivation, 140-142 P Page, Irvine H., et al., 59, 63 pain sensitivity, 139-140 pancreatectomy in different animals, 96-97, 96t pancreatic duct, 23-24, 25f pantothenic acid, 174-176, 253 Papper, E M., 139 paralysis, familial periodic, 154 parasites, 148-150 parathyroid glands, 93-94 paresis, 229-230 Park, E A., 167, 168 Parry of Bath, 2, 193 Paul, Henry E., 164 Paul, Mary F., 164 pellagra, 232 Pennes, Harry H., 138 pepsinogen excretion, 116 peptidases in erythrocytes, 82 pertussis vaccine, 127-128, 127t pervitin, 228 Pett, L B., 173 pharmacological response variation See drugs, response to phenolsulfatase in serum, 81 D-phenylalanine, 84-86, 85t phenylthiocarbamide (PTC), 144-145 physostigmine, 124-125 Pincus, Gregory, 98 pitiuitary gland, 102-106, 102t diabetes and, 95-96 thyroid-stimulating hormone of, 91-92 plant biology, 206 plasma catalase, 81 poliomyelitis, 216 Popper, Hans, 164-165 potassium cyanide smell, 147 potassium needs, 153-154, 199 prolactin, 103-104 propetology, 244 psychiatry, 225-237 brain anatomy and, 226-227 endocrine disorders/imbalances and, 230-231 mental health, 228, 237 paresis manifestations, 229-230 physiologically active drugs and, 228-229 Page 265 psychoneuroses, 232, 233 psychology, 205 pyruvate metabolism, rats, 86 Q quinine, taste, 145 R rabbits, organ weights of, 19-20, 20t, 29 radiation effects, 130-131 Ramsaroop, A., 138 Reader's Digest, 243 Reifenstein, Edward C., Jr., 98 research, medical, 209-223 arthritis, 215-216 dental caries, 218-221 gout,213-215 mental health, 237 metabolic peculiarities and, 210-212 reserpine, 228 respiratory tract, 37-39 rhythms (circadian), 196 riboflavin, 173-174 mutant without, 10-11 Richter, Curt P., 123, 145 rickets, 166-167 Riddle, Oscar, 21, 90, 91, 103 Roger J Williams Nutrition Institute for Disease Prevention Research and Education, 254255 Ronzoni, Ethel, 230 Rose, William C., et al., 161 Ryssing, E., 115 S saccharine, taste of, 145 saliva composition, 64-65, 65t, 66t Saul, Leon J., 139 Sawitsky, Arthur, et al., 79-80 schizophrenia, 227, 228, 232 genetic origins, 235-236 serotonin and, 236-237 Schneider Index, 45 Schull, William Jackson, 32 sciatic nerve, 45 sciences, applied, 202-208 See also research, medical biochemical individuality and, 206-207 metabolism, 203 variations, exceptions and, 202 vision, 202-203 vitamin research and, 204-205 scopolamine, 228 scurvy, 167-168 self-esteem, genetics and, 16 self-selection of foods, 180 Selye, Hans, 230 senile dementia, 34-35, 227, 230 sensory physiology and psychology, 205 serotonin, 236 serum amylase, 80-81 serum lipase, 81 serum phenolsulfatase, 81 sex behavior, 100, 104-105 psychiatry and, 231 sex differences in choline needs, 178 musculature, 42-44, 44t Shaw, E., 236 Shaw, James H., 220-221 sheep corpuscles, potassium and sodium in, 54, 56t Sheldon, William Herbert, 194-195 body types, 216-217 Sherman, Henry C., et al., 163 Siegle, F L., 244 Simmons, Dean, 237 sinuses, paranasal, 37-39, 38f, 39f skin composition, 71 smell, variations in, 147, 205 social sciences, 200, 253 sodium amytal, 228 Page 266 sodium benzoate, taste of, 145-146 somatotypes, 194, 216-217 Sperry, Warren M., 59 Spies, Tom D., 166, 177 spinal cord, 45 splanchnic nerves, 45, 47 starvation, 232 statistics, variation and, Steggerda, F R., 155 Steigmann, Frederick, 165 Stein, William H., 115 steroid excretion, 100-102, 116 Stieglitz, Julius, 251 Stockard, Charles Rupert, 89, 91, 92-93 stomachs, variation in, 22, 22f, 23, 24f sugar consumption, 181-182, 184 taste reactions to, 145 Sunderman, F William, 153 susceptibility, disease, 193-195, 217 dental caries, 218-220 Sutton, H Eldon, 110 symbionts, 148-150 syphilis, 229 T Tappan, D V., et al., 174 taste sensitivities, 4, 144-147 barium sulfate, 147 changing, 146-147 phenylthiocarbamide (PTC) and, 144-145 sodium benzoate, 145-146 Tatum, E L., temperature control patterns, 138-139 testes, 99 thiamine, 169-173 deficiencies of, 171-172, 233 thyroid gland, 90-93 tissue, drug responses to, 119-120 trace elements, 157-160 in blood, 55t, 57 cobalt, 160 copper, 157-159 iodine, 157 zinc, 159-160 transplantation experiments, 150 Trevorrow, Virginia, 54 Trufant, Samuel A., 230 tryptophane, niacin and, 174 Tuba, Jules, et al., 78 tuberculosis, 193, 216 Turgenev, 38 twins, identical, 8, 12, 110 Two Years Before the Mast, 167 typhoid, 193 carriers, 148 survival and, 194f U ulcers, 216 umbilical cord, 72 Unglaub, Walter G., et al., 177 "Unity of Knowledge" conference, 200 V Vallee, Bert L., 157-158 Vanderberg, Steven G., 110 variation, biochemical, 1-7 See also individuality, biochemical as an enemy, 204-206 blood differences, 3-4 deviates, 6-7 normal ranges and, 2-4 quantitative research and, 204, 205 research into, vertebral anatomy, 45 vision, 202-203 vitamin A, 162-166, 169, 199 animal studies, 163-164 growth rate relationship to intake of, 166f human needs award contest, 162-163 ... Significance in Biology and Medicine II Genetic Basis of Biochemical Individuality III Anatomical VariationsSignificance 19 IV Individuality in Composition 51 V Individual Enzymic Patterns 77 VI... WILLIAMS AUSTIN TEXAS Page xix To Benjamin Clayton whose supportmoral and material has been invaluable Page I Biochemical Variation: Its Significance in Biology and Medicine Since the days of. .. widespread existence of critical individual needs which can often be cared for if they are recognized Although ancients and moderns alike have called attention to variability and individuality as factors