“THIS MAY BE THE MOST IMPORTANT BOOK ON HEALTH EVER WRITTEN” National Health Federation Bulletin - THE HEALING FACTOR VITAMIN C Against Disease By Irwin Stone With forewords by Nobel Prizewinners Dr. Linus Pauling and Dr. Albert Szent-Gyorgyi Vitamin C may save your life! A noted biochemist reveals for laymen the exciting research into ascorbic acid’s powers against such deadly enemies as cancer, heart disease, strokes, mental illness, old age, diabetes, arthritis, kidney disease, hepatitis – even cigarette smoking! AGING – ALLERGIES ASTHMA – ARTHRITIS – CANCER COLDS – DIABETES & HYPOGLYCEMIA EYE TROUBLE – HEART DISEASE – STROKES KIDNEY & BLADDER AILMENTS – MENTAL ILLNESS STRESS SYNDROMES – POISONING – POLLUTION ULCERS – VIRUSES WOUNDS & FRACTURES SHOCK COULD THEY BE THE RESULT OF VITAMIN C DEFICIENCY? COULD THEY BE PREVENTED BY TAKING MORE VITAMIN C? COULD THEY BE TREATED WITH VITAMIN C? IS VITAMIN C REALLY A VITAMIN? IRWIN STONE SAYS YES, YES, YES AND NO! After 40 years research, Irwin Stone unfolds his startling conclusion that an ancient genetic mutation has left the primate virtually alone among animals in not producing ascorbic acid (Vitamin C) in his own body. By treating it as a “minimum daily requirement” instead of the crucial enzyme it really is, we are living in a state of sub-clinical scurvy whose symptoms have been attributed to other ailments. The answer is to change our thinking about Vitamin C and consume enough to replenish this long-lost “healing factor.” Stone illustrates, with massive documentation, Vitamin C’s remarkable ability to fight disease, counteract the ill effects of pollution and prolong healthy life – easily and inexpensively! GD/Perigee Books are published by The Putnam Publishing Group ISBN 0-399-50764-7 Copyright © 1972 by Irwin Stone This book is dedicated to my wife, Barbara whose patience and collaboration over the years made it possible. CONTENTS Forewords Linus Pauling Albert Szent-Gyorgyi Acknowledgements Introduction Part I: Our Deadly Inheritance 6.The Nineteenth and Early Twentieth Centuries 1.The Beginnings of Life (omitted) 7.Finding the Elusive Molecule 2.From Fishes to Mammals (omitted) 8.The Genetic Approach 3.Our Ancestral Primate (omitted) 9.Some Effects of Ascorbic Acid 4.The Evolution of Man (omitted) 10. ”Correcting” Nature 5.From Prehistory to the Eighteenth Century Part II: Pathways to Research 14. Bacterial Infection 11. Breaking the “Vitamin” Barrier 15. Cancer 12. The Common Cold 16. The Heart, Vascular System, and Strokes 13. Viral Infection 17. Arthritis and Rheumatism 18. Aging 25. Physical Stresses 19. Allergies, Asthma, and Hay Fever 26. Pollution and Smoker’s Scurvy 20. Eye Conditions 27. Wounds, Bone Fractures, and Shock 21. Ulcers 28. Pregnancy 22. Kidneys and Bladder 29. Mental Disease 23. Diabetes and Hypoglycemia 30. The Future 24. Chemical Stresses – Poisons, Toxins References Cited from the Medical Literature Glossary The numerals set off in parenthesis in the text are intended to guide the reader to the appropriate medical citation listed at the end of the book. FOREWORD by Linus Pauling, Ph.D. Nobel Laureate This is an important book – important to laymen, and important to organization which could and would arrange such studies. Our society physicians and scientists interested in the health of people. spends billions or trillions on killing and destruction but lacks the relatively modest means demanded to keep its own health and prime interest cared Irwin Stone deserves much credit for having marshalled the arguments that for. Full health, in my opinion, is the condition in which we feel best and indicate that most human beings have been receiving amounts of ascorbic show the greatest resistance to disease. This leads us into statistics which acid less than those required to put them in the best of health. It is his demand organization. But there is another, more individual difficulty. If contention, and it is supported by much evidence, that most people in the you do not have sufficient vitamins and get a cold, and as a sequence world have a disease involving a deficient intake of ascorbic acid, a disease pneumonia, your diagnosis will not be “lack of ascorbic acid” but that he has named hypoascorbemia. This disease seems to be present “pneumonia.” So you are waylaid immediately. because of an evolutionary accident that occurred many millions of years ago. Ancestors of human beings (and of their close present-day relatives, I think that mankind owes a serious thanks to Irwin Stone for having kept other primates) were living in an area where the natural foods available the problem alive and having called Linus Pauling’s attention to it. provided very large amounts of ascorbic acid (very large in comparison On my last visit to Sweden, I was told that the final evidence has been with the amounts usually ingested now and the amounts usually found that ascorbic acid is quite harmless. An insane person had the fixed recommended now by physicians and other authorities on nutrition). A idea that he needed ascorbic acid so he swallowed incredible amounts of it mutation occurred that removed from the mutant the ability to manufacture for a considerable period without ill effects. So, apart from very specific ascorbic acid within his own body. Circumstances were such that the conditions, ascorbic acid cannot hurt you. It does not hurt your pocket mutant had an evolutionary advantage over the other members of the either, since it is very cheap. It is used for spraying trees. population, who were burdened with the machinery for manufacturing additional ascorbic acid. I also fully agree with Dr. Pauling’s contention that individual needs for vitamin C vary within wide limits. Some may need high doses, others may The result was that the part of the population burdened with this machinery be able to get along with less, but the trouble is that you do not know to gradually died out, leaving the mutants, who depended upon their food for which group you belong. The symptoms of lack may be very different. I an adequate supply of ascorbic acid. remember my correspondence with a teacher in my earlier days who told me As man has spread over the earth and increased in number, the supplies of that he had an antisocial boy whom he was unable to deal with. He gave ascorbic acid have decreased. It is possible that most people in the world him ascorbic acid and the boy became one of his most easygoing, obedient receive only one or two percent of the amounts of ascorbic acid that would pupils. Nor does wealth and rich food necessarily protect against lack of keep them in the best of health. The resulting hypoascorbemia may be vitamins. I remember my contact with one of the wealthiest royal families responsible for many of the illnesses that plague mankind. of Europe where the young prince had constant temperature and had poor health. On administering vitamin C, the condition readily cleared up. In this book, Irwin Stone summarizes the evidence. The publication of Irwin Stone’s papers and of this book may ultimately result in a great It gives me great satisfaction to see this book appear and I hope very much improvement in the health of human beings everywhere, and a great that its message will be understood. decrease in the amount of suffering caused by disease. Albert Szent-Gyorgyi - Linus Pauling - ACKNOWLEDGMENTS FOREWORD This book took many years to write and involved many people. Because of by Albert Szent-Gyorgyi, M.D., Ph.D. Nobel Laureate a nonexistent budget and the fact that much of the data was in foreign My own interest in ascorbic acid centered around its role in vegetable languages, good friends had to be relied upon to supply translations. respiration and defense mechanisms. All the same, I always had the feeling Among these friends were Lotte and George Bernard, Helene Gottlieb, that not enough use was made of it for supporting human health. The Dorothy Kramer, Irving Minton, Jutta Nigrin, Sal Scaturo, Tanya Ronger, reasons were rather complex. The medical profession itself took a very and Natasha and Otmar Silberstein. narrow and wrong view. Lack of ascorbic acid caused scurvy, so if there Invaluable help and advice on library work were supplied by Eliphal was no scurvy there was no lack of ascorbic acid. Nothing could be clearer Streeter and Vera Mitchell Throckmorton. The medical library of the Statin than this. The only trouble was that scurvy is not a first symptom of lack Island Public Health Hospital and the reprint facilities of the National but a final collapse, a premortal syndrome, and there is a very wide gap Library of Medicine and the Medical Research Library of Brooklyn were between scurvy and full health. But nobody knows what full health is! especially helpful. This could be found out by wide statistical studies, but there is no In any radically new scientific concept, encouragement and inspiration to My wife Barbara, in the latter years, handled the bulk of the library carry on are difficult to come by. The author was fortunate in having men research. To all these people and to many others who have contributed, go of scientific or medical stature such as Linus Pauling, Albert Szent-Gyorgyi, my deep gratitude and thanks. I trust that their efforts effectively contribute Frederick R. Klenner, Abram Hoffer, William J. McCormick, Thomas A. to better health for man. Garrett, Walter A. Schnyder, Louis A. Wolfe, Alexander F. Knoll, Marvin Discovery consists in seeing what everybody else has seen and thinking D. Steinberg, Benjamin Kramer, and A. Herbert Mintz as pillars of strength. what nobody has thought. Miriam T. Albert Szent-Gyorgyi Malakoff and Martin Norris supplied editorial advice and encouragement. INTRODUCTION The purpose of this book is to correct an error in orientation which occurred relating to the use of ascorbic acid in diseases other than scurvy, but only in 1912, when ascorbic acid, twenty years before its actual discovery and very little practical therapeutic information has developed pertaining to its synthesis, was designated as the trace nutrient, vitamin C. Thus, in the successful use in these diseases. The reader may well ask what is the discussions in this book the terms “vitamin C” and “ascorbic acid” are difference between data and information? This can be illustrated by the identical, although the author prefers to use “ascorbic acid.” following example: the number 382,436 is just plain data, but 38-24-36, that is information. Scurvy, in 1912, was considered solely as a dietary disturbance. This hypothesis has been accepted practically unchallenged and has dominated The most probable reason for the paucity of definitive therapeutic ascorbic scientific and medical thinking for the past sixty years. The purpose of this acid information in the therapy of diseases other than scurvy is related to vitamin C hypothesis was to produce a rationale for the conquest of frank the fact that the vitamin C-oriented investigators were trying to relieve a clinical scurvy. That it did and with much success, using minute doses of trace-vitamin dietary disturbance and never used doses large enough to be vitamin C. Frank clinical scurvy is now a rare disease in the developed pharmacologically and therapeutically effective. The new genetic concepts countries because the amounts of ascorbic acid in certain foodstuffs are currently correct this old, but now obvious, mistake by supplying a logical sufficient for its prevention. However, in the elimination of frank clinical rationale for these larger, pharmacologically effective treatments. scurvy, a more insidious condition, subclinical scurvy, remained; since it If the research suggestions contained in this book are properly and was less dramatic, it was glossed over and overlooked. Correction of conscientiously followed through, it is the hope of the author that future subclinical scurvy needs more ascorbic acid than occurs naturally in our medical historians may consider this as a major breakthrough in medicine of diet, requiring other non-dietary intakes. Subclinical scurvy is the basis for the latter quarter of the twentieth century. many of the ills of mankind. While many scientific and medical papers have appeared, the publication of Because of this uncritical acceptance of a misaligned nutritional hypothesis, Dr. Linus Pauling’s book, Vitamin C and the Common Cold, in late 1970 the bulk of the clinical research on the use of ascorbic acid in the treatment was the first scientific book ever published in the new medical fields of of diseases other than scurvy has been more like exercises in home megascorbic prophylaxis and megascorbic therapy, which are branches of economics than in the therapy of the sequelae of a fatal, genetic liver- orthomolecular medicine. Dr. Pauling’s book paved the way for this enzyme disease. volume. One of the objects of this book is to take the human physiology of ascorbic Since the size of the daily intake of ascorbic acid is so important in the later acid out of the dead-end of nutrition and put it where it belongs, in medical discussions, the reader can refer to the following table of equivalents. The genetics. In medical genetics, wide vistas of preventive medicine and dosages are usually expressed in the metric system in milligrams or grams therapy are opened up by the full correction of this human error of of ascorbic acid: carbohydrate metabolism. For the past sixty years a vast amount of medical data has been collected Common MeasuresMetric Equivalents -MilligramsMetric Equivalents -Grams 1000 1 1 ounce2835028.35 ½ teaspoonful*1,500 to 2,0001.5 to 2.0 20 international units10.001 *teaspoons vary in size PART I Note: for the sake of our Christian readers I have omitted the author's cannot make ascorbic acid in his liver. interminable speculations about how “evolution” brought about the This was a serious mutation because organisms without ascorbic acid do not important facts below. last very long. However, by a fortuitous combination of circumstances, the In nearly all the mammals, ascorbic acid is manufactured in the liver from animal survived. First of all, the mutated animal was living in a tropical or the blood sugar, glucose. The conversion proceeds stepwise, each step semitropical environment where fresh vegetation, insects, and small animals being controlled by a different enzyme. The mutation that occurred in our were available the year round as a food supply. All these are good dietary ancestral monkey destroyed his ability to manufacture the last enzyme in sources of ascorbic acid. Secondly, the amount of ascorbic acid needed for this series – L-gulonolactone oxidase. This prevented his liver from mere survival is low and could be met from these available sources of food. converting L-gulonolactone into ascorbic acid, which was needed to carry This is not to say that this animal was getting as much ascorbic acid from its out the various biochemical processes of life. The lack of this enzyme made food as it would have produced in its own body if it had not mutated. this animal susceptible to the deadly disease, scurvy. To this day, millions While the amount may not have been optimal, it was sufficient to ward off of years later, all the descendants of this mutated animal, including man, death from scurvy. Under these ideal conditions the mutation was not have the intermediate enzymes but lack the last one. And that is why man serious enough to have too adverse an effect on survival. It was only later when this animal’s descendants moved from these ideal surroundings, this and what their methods of food preparation and preservation were before Garden of Eden, and became “civilized” that they – we – ran into trouble. “civilization” reached them: the Australian aborigine, the native tribes of Africa, the Indians of the Americas, and the Eskimo, who has worked out a This defective gene has been transmitted for millions of years right up to the pattern for survival in a most unfavorable environment. present-day primates. This makes man and a few other primates unique among the present-day mammals. Nearly all other mammals manufacture In reviewing the diets of these peoples, one is impressed by their variety. ascorbic acid in their livers in amounts sufficient to satisfy their All products of the plant and animal kingdoms,without exception, were at physiological requirements. This had great survival value for these one time or another consumer. Those who ate their food fresh and raw had mammals, who, when subjected to stress, were able to produce much larger more chance of obtaining ascorbic acid. Extended cooking or drying tends amounts of ascorbic acid to counteract adverse biochemical effects. And to destroy ascorbic acid. The availability of food appears to have been the there was plenty of stress for an animal living in the wild, competing for main factor in an individual’s nutrition and, aside from certain tribal taboos, scarce food, and trying to avoid becoming a choice morsel for some other there were no aesthetic qualms against eating any kind of food. A luscious predator. spider’s abdomen bitten off and eaten raw, a succulent lightly toasted locust consumed like a barbecued shrimp, the larva of the dung beetle soaked in To the best of our knowledge, only two other non-primate mammals have coconut milk and roasted were good sources of ascorbic acid. Similarly, suffered a similar mutation and have survived. How many others may have raw fish, seaweed, snails, and every variety of marine mollusk were tasty similarly mutated and died off, we shall never know. The guinea pig morsels for those peoples living near the shores. survived in the warm lush forests of New Guinea where vegetation rich in fresh ascorbic acid was readily available. The other mammal is a fruit- The name “Eskimo” comes from the Cree Indian work “uskipoo,” meaning eating bat (Pteropus medius) from India. The only other vertebrates that are “he eats raw meat.” During the long winter, Eskimos depended upon the known to harbor this defective gene are certain passeriforme birds. ascorbic acid content of raw fish or freshly caught raw seal meat and blood. Any Eskimo who cooked his fish and meat – thereby reducing its ascorbic Because of this missing or defective gene, man, some of the other primates, acid content – would never have survived long enough to tell about his the guinea pig, and a bat will develop and die of scurvy if deprived of an new-fangled technique of food preparation. But, not even the best of these outside source of ascorbic acid. A guinea pig, for example, will die a diets ever supplied ascorbic acid in the amounts that would have been horrible death within two weeks if totally deprived of ascorbic acid in its produced in man’s own liver if he had the missing gene. The levels were, as diet. always, greatly submarginal for optimal health and longevity, especially The evolution of the nervous system and the explosive development of the under high-stress conditions. The estimated life expectancy for an Eskimo brain and intelligence compensated in some measure for this biochemical man in northern Greenland is only twenty-five years. defect by finding new sources of ascorbic acid. The normally herbivorous Two great advances in the early history of man were the development of and insect-eating species became hunters after raw red meat and fish, and agriculture and the domestication of animals. In the temperate zones, later went on to raise their own animals. It was this change in dietary agriculture tended to concentrate on cereal grains or other seed crops, which practice that permitted the wide dispersion of the humanoids. They were no could easily be stored without deterioration and used during the long longer limited to tropical or semitropical areas where plants or insects rich winters. These crops are notably lacking in ascorbic acid and, while they in ascorbic acid were available the year round. To gauge the effect of this supplied calories, scurvy would soon develop in those who depended on factor, just compare the wide dispersion of man on the face of this globe them as a staple diet. Whatever fresh vegetables or fruits were grown were with his less adaptable primate relatives, the monkeys and apes. They are generally rendered useless as an antiscorbutic foodstuff for winter use by still swinging in the branches close to their supply of ascorbic acid. the primitive methods of drying and preservation. This dispersal of primitive man into environs for which he was not A trick for imparting antiscorbutic qualities to seed crops was discovered by biochemically adapted was not easy and was only accomplished at a high various agricultural peoples and then forgotten. It was rediscovered again cost – increased mortality, shortened life span, and great physical suffering. in Germany in 1912, and it has persisted among some Asiatic people. This Man’s survival under these unfavorable conditions is a tribute to this guts simple life-saving measure was to take portions of these seed crops (beans and brainpower. Here was one of Nature’s first experiences with an and the like), soak them in water, and then allow them to germinate and organism that could fight back against an unfavorable environment and sprout. The sprouted seeds were consumed. Ascorbic acid is required by win. But the victory, as we can see all around us, was a conditional one. the growing plant and it is one of the first substances that is synthesized in A study of the remains found in ancient burial grounds reveals some of the the growing seed to nourish the plant embryo. Bean sprouts are even now a privations suffered by Stone Age man and his descendants. Living in the common item of the Chinese cuisine as they have been for thousands of temperate zone, the cold was a constant threat to his existence. The years; but they contain our elusive molecule, while unsprouted beans do exhumed bones give evidence of much disease, nutritional deficiencies, and not. general starvation. Infant and child mortality was enormous, and the life The early people whose culture was based upon animal husbandry may span of those who survived their teens was rarely beyond thirty or thirty- have fared better in the winter than the agricultural people. They had a five years. Some abnormalities evidenced in the fossilized limbs of these built-in continuous ascorbic acid supply in their fresh milk, fresh meat, and ancient populations could have been caused by recurring episodes of blood. If they used these products fresh they were safe, but if they inadequate intake of ascorbic acid. Future studies in paleopathology should attempted long preservation, the antiscorbutic properties were lost and the bring additional interesting facts to light. foodstuffs became potential poisons. Another way of assessing the extent of the ascorbic acid nutriture of these All in all, it has been a terrible struggle throughout prehistory and history to ancient peoples is to find out what current primitive societies used as food, obtain the little daily speck of ascorbic acid required for mere survival 5. FROM PREHISTORY TO THE EIGHTEENTH CENTURY Now we come to man in historical times and find that he has been plagued In describing the disease we must distinguish between chronic scurvy and by the effects of this genetic defect from the earliest days of recorded acute scurvy. Chronic or biochemical scurvy is a disease that practically history. everyone suffers from and its individual severity depends upon the amount of one’s daily intake of ascorbic acid. It is a condition where the normal Before discussing this great scourge of mankind, let us examine the disease biochemical processes of the body are not functioning at optimal levels caused by this genetic defect. Clinical scurvy is such a loathsome and fatal because of the lack of sufficient ascorbic acid. There are all shades of affliction that it is difficult to conceive that an amount of ascorbic acid that biochemical scurvy and it can vary from a mild “not feeling right” to could be piled upon the head of a pin is enough to prevent its fatal effects. conditions where one’s resistance is greatly lowered and susceptibility to disease, stress, and trauma is increased. affected. It was scurvy that led to the ultimate defeat and capture of Saint Louis and his knights. It is certain that, throughout the Crusades, scurvy The chronic form usually exists without showing the clinical signs of the took a far greater toll of the Crusaders than all the weapons of the Saracens. acute form and this makes it difficult to detect and diagnose without special biochemical testing procedures. The acute form is the “classical” scurvy In the great cycle of epidemics that hit Europe in the fourteenth century – recognized from ancient times and is due to prolonged deprivation of the Black Death of the Middle Ages – millions of people died. The Black ascorbic acid, usually combined with severe stress. Death was a fulminating, virulent epidemic of a bacterial disease, bubonic plague, concurrent with pulmonary infection superimposed on scurvy with The first symptom of acute scurvy in an adult is a change in complexion: its diffused superficial hemorrhages that caused the skin to turn black or the color becomes sallow or muddy. There is a loss of accustomed vigor, bluish-black. The fact that the disease attacked a population that was first increased lassitude, quick tiring, breathlessness, a marked disinclination for thoroughly weakened by scurvy accounts for the extremely high mortality: exertion, and a desire for sleep. There may be fleeting pains in the joints one-fourth of the population of Europe – or 25 million deaths. It is known and limbs, especially the legs. Very soon the gums become sore, bleed that resistance to infection is lowered by a deficiency of ascorbic acid, so a readily, and are congested and spongy. Reddish spots (small hemorrhages) disease which would normally be a mild affliction could whip through a appear on the skin, especially on the legs at the sites of hair follicles. scorbutic population with unprecedented fierceness and fatally strike down Sometimes there are nosebleeds or the eyelids become swollen and purple thousands. or the urine contains blood. With the invention of the printing press and the easier dissemination of the These signs progress steadily – the complexion becomes dingy and printed word, the sixteenth and following centuries saw the appearance of brownish, the weakness increases, with the slightest exertion causing many tracts that described scurvy and its bizarre causes, and offered many palpitation and breathlessness. The gums become spongier and bleed, the different exotic treatments and “cures” for the disease. Much earlier, teeth become loose and may fall out, the jawbone starts to rot,and the breath folklore had associated scurvy with a lack of fresh foodstuffs, and the is extremely foul. antiscorbutic qualities of many plants had been known. But these qualities Hemorrhages into any part of the body may ensue. Old healed wounds and were forgotten and had to be rediscovered again and again at a great cost in scars on the body may break open and fresh wounds and sores show no lives and suffering. tendency to heal. Improved ship construction and the ensuing long voyages provided ideal Pains in the limbs render the victim helpless. The gums swell so much that conditions for the rapid development of acute scurvy under circumstances they overlay and hide the teeth and may protrude from the mouth. The where the developing symptoms could be readily observed and recorded. bones become so brittle that a leg may be broken by merely moving it in Sailors quickly succumbed to scurvy due to inadequate diet; physical bed. The joints become so disorganized that a rattling noise can be heard exertions; exposure to extremes of heat, cold, and dampness; and the from the bones grating against each other when the patient is moved. Death generally unsanitary shipboard conditions. In a few short months, out of usually comes rapidly from sudden collapse at slight exertion or from a what started off as a seemingly healthy crew, only a few remained fit for secondary infection, such as pneumonia. This sequence of events, from duty and were able to stand watch. apparent health to death, may take only a few months. The logs of these voyages make incredible reading today. Before scurvy Acute clinical scurvy was recognized early by ancient physicians and was was finally controlled, this scourge destroyed more sailors than all other probably known long before the dawn of recorded history. Each year in the causes, including the extremely high tolls of naval warfare. colder climes, as winter closed in, the populations were forced onto a diet of In 1497, Vasco da Gama, while attempting to find a passage to the Indies by cereal grains and dried or salted meat or fish, all low in ascorbic acid. way of the Cape of Good Hope, lost 100 of his 160-man crew to scurvy. Foods rich in ascorbic acid were scarce if not entirely lacking. The Magellan, in 1519, set sail with a fleet of five ships on one of history’s great consequence of this inadequate diet was that near the end of winter and in voyages, the circumnavigation of the earth. Three years later, only one early spring, whole populations were becoming increasingly scorbutic. ship, with only eighteen members of the original crew, returned to Spain. Thus weakened, their resistance low, people were easy prey for the rampant On occasion, a Spanish galleon would be found drifting, a derelict, its entire bacterial and viral infections that decimated the population. This happened crew dead of scurvy. Many books were written on scurvy during the year after year for centuries and this is the origin of the so-called “spring sixteenth to eighteenth centuries; some authors hit upon means to actually tonics,” which were attempts to alleviate this annually recurring scurvy (by combat the disease, while others, clouded by the medical lore of the times, measures which were generally ineffective). The number of lives lost in were way off base. this annual debacle and the toll in human misery are inestimable. People became so accustomed to this recurring catastrophe that it was looked upon We still find logs of eighteenth-century voyages that recount the devastating as the normal course of events and casually accepted as such. Only in times effects of scurvy, and others where the master of the ship was able to of civil strife, of wars and sieges, or on long voyages, where the toll in lives prevent the disease. In 1740, Commodore Anson left England with six lost to this dread disease was so great, did it merit special notice. vessels and 1500 seamen; he returned four years later with one ship and 335 men. Between 1772 and 1775, on his round-the-world trip, however, Figure 2 Captain James Cook lost only one man out of his crew of 118, and that one Egyptian hieroglyphs believed to indicate scurvy not from scurvy. Cook took every opportunity when touching land to obtain supplies of fresh vegetables and fruit. The earliest written reference to a condition that is recognizable as scurvy is in the Ebers papyrus, a record of Egyptian medical lore written about 1500 He usually had a good store of sauerkraut aboard and he knew the B.C. beneficial qualities of celery and scurvy grass. After the voyage was completed, Cook was presented with the Copley Medal of the Royal Figure 2 shows various Egyptian hieroglyphs for scurvy. The figure of the Society. This award was given for his success in making such a lengthy little man pointing to his mouth and the lips oozing blood indicated the voyage without a single death from scurvy – not for his great navigational bleeding gums of the disease. It is likely that scurvy was clearly recognized and geographic discoveries. His scientific contemporaries understood the at least 3,000 years ago. Hippocrates (ca. 400 B.C.), the father of medicine, great significance of Cook’s accomplishment. described diseases that sounded suspiciously like scurvy. Pliny the Elder (A.D. 23-79), in his Natural History, describes a disease of Roman soldiers Between the time of Anson’s failure and Cook’s great success another in Germany whose symptoms bespeak of scurvy and which was cured by a important event took place; the first modern type of medical experiment was plant herba Britannica. Sire Jean de Joinville, in his history of the invasion carried out by James Lind. We will discuss this later. of Egypt by the Crusaders of Saint Louis in 1260, gives a detailed This is only a very brief record of the easily avoidable havoc caused by description of the scurvy that afflicted this army. He mentions the scurvy on the high seas, but those on land fared little better. In addition to hemorrhagic spots, the fungous and putrid gums, and the legs being the fearful, annually recurring scorbutic devastation of the population in the late winter and early spring, there were special circumstances which been adequately evaluated. In this case Lind did as much as Nelson to brought on deadly epidemics of acute scurvy. Wars and long sieges break the power of Napoleon. The English vessels were able to maintain brought these epidemics to a head. In a brief sampling of the wars of the continuous blockade duties, laying off the coast of France for months at a sixteenth to eighteenth century, scurvy appeared at the siege of Breda in time without the necessity of relieving the men. Were it not for Lind, the Holland in 1625 and at Thorn in Prussia in 1703, where it accounted for flat-bottomed invasion barges assembled by Napoleon may well have 5,000 deaths among the garrison and noncombatants. It took its toll of the crossed the English Channel. Russian armies in 1720 in the war between the Austrians and the Turks, of the English troops that captured Quebec in 1759, and of the French soldiers 6. THE NINETEENTH AND EARLY TWENTIETH CENTURIES in the Alps in the spring of 1795. One would imagine that Lind’s clear-cut clinical demonstration and the Witness also Jaques Cartier’s expedition to Newfoundland in 1535. These experiences of the Royal Navy in wiping out the disease would have were men from a civilized culture with a long background of medical lore. pointed the way toward banishing this disease completely. However, it One hundred of Cartier’s 110 men were dying of scurvy until the Indian takes much more than logic and clear-cut demonstrations to overcome the natives showed him how to make a decoction from the tips of spruce fir inertia and dogma of established thought. The forty-two years that it took which cured his men. This trick, incidentally, was also used by the the British Admiralty to adopt Lind’s recommendations may seem unduly defenders of Stalingrad in World War II to stave off scurvy. long, even for a stolid bureaucracy, but this may be a speed record compared with other agencies. The British Board of Trade took 112 years – By the middle of the eighteenth century ,the stage had been prepared for until 1865 – before similar precautions were adopted for the British advances in the prevention and treatment of scurvy. Admiral Sir Richard merchant marine. There are records of seamen on the merchant vessels Hawkins, in 1593, protected the crew of the Dainty with oranges and succumbing to scurvy even while delivering lemons to the ships of the lemons; among others, Commodore Lancaster, in voyages for the East India Royal Navy. Over 30,000 cases of scurvy were reported in the American Company, had shown by 1600 that scurvy was an easily preventable Civil War and it took the U.S. Army until 1895 to adopt antiscorbutic disease. It remained, however, for James Lind to prove this. James Lind, rations. surgeon’s mate on H.M.S. The saga of scurvy continues, with its incredible toll in human lives and Salisbury, was inspired by the hardships of the Anson fiasco and the many suffering, up to the present day. In the nineteenth century, 104 land cases of scurvy he had treated on his own ships. Lind was a keen observer epidemics have been tabulated. And the twentieth century has had plenty of and eventually became known as “the father of nautical medicine.” He trouble with the disease, not only as a result of the World Wars but in civil conducted the first properly controlled clinical therapeutic trial on record. populations, as a result of ignorance and improper use of food. The crucial experiment Lind performed in 1747 at sea on the Salisbury, was In the latter part of the nineteenth century Barlow’s disease became to take twelve seamen suffering from the same degree of scurvy and divide prevalent, and it was recognized as infantile scurvy. It appeared at the time them into six groups of two each. In addition to their regular diet, he gave when artificial feeding of babies was becoming popular, and took the name each group a different, commonly used treatment for scurvy and observed of the doctor who described the disease in 1883. Actually, the disease was its action. first described in 1650, but it was confused with rickets until Barlow’s clear One group received a quart of cider daily, the second group received differentiation. There were so many cases that it was also known as twenty-five drops of dilute sulfuric acid three times a day, the third group Mueller’s or Cheadle’s disease. Breast-fed babies did not appear to get the was given two spoonfuls of vinegar three times a day, the fourth team drank disease, but those fed with boiled and heated cow’s milk or with cereal half a pint of seawater three times a day, the fifth received a concoction of substitutes did. It is an intensively painful disease and results in stunted garlic, mustard seed, horseradish, gum myrrh, and balsam of Peru. The last growth and delayed development. The disease persists to the present day group received two oranges and one lemon daily for six days. These last and is amenable to the same preventive and curative measures as adult two men improved with such astonishing rapidity that they were used as scurvy – the speck of ascorbic acid contained in fresh fruits and vegetables. nurses to care for the others. Here again the lesson had to be relearned, the hard way, with babies put in the same class as seamen. There was slight improvement in the cider group but no benefit was observed in the others. Here was clear-cut, easily understandable evidence Scurvy and its treatment has had many ups and downs during the long of the value of citrus fruit in the cure of scurvy. Although Lind did not history of man, and one series of events in the nineteenth century raised realize it, he had found a good natural source of our elusive molecule. some mistrust in the prophylactic powers of fresh fruits. This is another example of the kind of mistaken conclusions based on confusion, Lind left the Royal Navy in 1748, obtained an M.D. Degree from incomplete observations, and improper interpretations which has cursed the Edinburgh University, and went into private practice. He was later history of scurvy. At the time this took place all knowledge of scurvy was physician at the Royal Naval Hospital at Haslar and physician to the Royal completely empirical; there was no experimental or quantitative data Household of George III at Windsor. He continued his work on scurvy and, because there were no experimental animals known that could be given in 1753, published one of the classics of medical literature, A Treatise of scurvy. We did not know any more than Lind knew a hundred years before. the Scurvy. What as clear to Lind, and is commonplace to us, was not so readily accepted by the naval bureaucracy of his day. It took over forty The English used the term “lime” indiscriminately for both lemons and years for the British Admiralty to adopt Lind’s simple prophylactic daily limes. In 1850, for political and economic reasons they substituted the dose of one ounce of lemon juice per man. West Indian lime for the traditional Mediterranean lemon used by the Royal Navy since 1795. We now know that the Mediterranean lemon is a good The official order cam through in 1795, just a year after Lind’s death. It has source of our elusive molecule, while the West Indian lime is not. In 1875 been estimated that this 42-year delay cost the Royal Navy 100,000 the Admiralty supplied a large amount of West Indian lime juice to Sir casualties to scurvy. George Nare’s expedition to discover the North Pole. An epidemic of This simple regimen wiped out scurvy in the naval forces of England, and it scurvy broke out and ruined the expedition. A commission was appointed became their secret weapon for maintaining their mastery of the seas. There to inquire into the cause of the disaster but could arrive at no satisfactory is no doubt that this simple ration of lemon juice was of far greater conclusion. It was even more perplexing because a previous Arctic importance to the Royal Navy of the eighteenth and nineteenth centuries expedition in 1850 (the date is important because lemons were used) had than all the improvements in speed, firepower, armor, and seaworthiness. spent two years of great hardships, but without scurvy. It took until 1919 to Naval officers of the time asserted that it was equivalent to doubling the finally resolve the cause of this debacle; in the meantime, however, this fighting force of the navy. Previously, because of the ravages of scurvy, the incident provoked a general and indiscriminate distrust of antiscorbutics – seagoing fleets had to be relieved every ten weeks by a freshly manned fleet especially among Polar explorers. On the Jackson-Harmsworth expedition of equal strength so that the scorbutic seamen could be brought home for of 1894-1897, a party carrying no lime juice, but eating large amounts of rehabilitation. The impact of our elusive molecule on history has never fresh bear meat, remained in good health. The crew left on the ship, taking their daily lime juice and subsisting on canned and salted meat, came down found that the guinea pigs rapidly came down with scurvy instead. This with scurvy. This led to the theory that scurvy was caused by tainted meat. was a startling discovery, because up to this point it was believed that man Thus, in 1913, the Antarctic explorer, Captain Scott, and his companions was the only animal that could contract scurvy. This was also a very suffered miserable deaths because their expedition was provisioned on the valuable and practical contribution because now an experimental animal basis of the tainted meat theory and carried no antiscorbutics. was available that could be used for all sorts of exact and quantitative studies of scurvy. It also showed that there was something very similar an Because of the lack of accurate knowledge concerning our elusive unique about the physiology of the guinea pig and man. This simple molecule, many other odd theories on scurvy were proposed, some as late observation was the greatest advance in the study of scurvy since the as the 1910s when we should have known better. One theory claimed that experiments of Lind in the 1740s. This discovery could have been made scurvy was due to an “acid intoxication” of the blood, another that it was a twelve years earlier had Theobald Smith, the famous American pathologist, bacterial autointoxication, and as late as 1916, someone “discovered” its realized the importance of his observation that guinea pigs fed a diet of oats bacterial origin. Probably the crowning nonsense was put forward in 1918, developed a hemorrhagic disease. But he failed to relate the bleeding of his when it was claimed that constipation was the cause of scurvy. After World guinea pigs with human scurvy. War I, two German doctors who had been assigned to care for Russian prisoners of war came up with the novel idea that scurvy was transmitted by There were many brilliant workers in the field of nutrition, but we need vermin; apparently the Russians had both. only mention one other in the thread of occurrences that led to the present misconceptions regarding our elusive molecule. Casimir Funk, working in Aside from these blunders, the nineteenth century saw many great advances the Lister Institute, prepared a highly concentrated rice-bran extract for the in the sciences. The germ theory of disease was established after much treatment of beriberi and designated the curative substance in this extract as initial resistance from the medical dogma of the time. And progress was a “vitamine.” In 1912-1913 he published his then radical theory that made in the scientific study of nutrition. A brief historical review of the beriberi, scurvy, and pellagra and possibly rickets and sprue were all science of nutrition will provide the reader with some background to better “deficiency diseases,” caused by the lack of some important specific trace understand the theme of this book. factor in the diet. Subsequent work divided these factors into three groups: In the early years of the nineteenth century, experiments were conducted in vitamin A, the fat-soluble antiophthalmic factor; vitamin B, the water- which animals were fed purified diets of the then known food constituents: soluble antineuritic substance; and vitamin C, the water-soluble fats, carbohydrates, and proteins. But the animals did not thrive. Not only antiscorbutic material. It was not known for many years whether each did they not grow well but they also developed an opacity of the cornea of vitamin represented a single substance or many. Vitamin B was later found the eye (which we now know is due to a vitamin A deficiency). Later in the to consist of a group of chemically diverse compounds, while both vitamin century, in 1857 in Africa, Dr. Livingstone noted a similar eye condition in A and vitamin C were single substances. Time added more “letters” to the poorly fed natives. Later, about 1865, similar observations were made of vitamin alphabet. Eventually the different vitamins were isolated, purified, slaves on South American sugar plantations. The condition was attributed and their chemical structures determined and finally synthesized: but this to some toxic constituent in their monotonous diet rather than the lack of took many years. some element. Most of the investigators in the growing science of nutrition In the early decades of the twentieth century, ascorbic acid was still concentrated on learning the basic facts about calories and the utilization of unknown. fats, carbohydrates, and proteins in the diet. Why a purified diet, adequate in these elements, would not support life, long remained a mystery. The sum total of our knowledge was about equal to Lind’s but great changes were in store. In the latter decades of the nineteenth century and early in the twentieth century, many important observations were made which helped unravel this 7. FINDING THE ELUSIVE MOLECULE mystery. The Japanese Tahaki showed that the disease beriberi, then afflicting 25 to 40 percent of the Imperial Japanese Fleet, could be In 1907, with the discovery that guinea pigs were also susceptible to scurvy, prevented by adding meat, vegetables, and condensed milk to the customary experimental work heretofore impossible could be conducted in the study of diet of rice and fish. He missed the significance of his results because he the disease. Foods could be assayed to determine the amounts of believed the improvement was due to a higher calorie intake comparable to antiscorbutic substance they contained. The general properties of our that of the German and British navies. In 1897, the Dutchman Eijkman, elusive molecule could be studied by using various chemical treatments on working in Batavia, was able to produce beriberi in chickens by feeding the antiscorbutic extracts and following them with animal assays to learn them polished rice (rice from which the husk coating is removed) and was why the molecule was so elusive and sensitive. able to cure the birds by giving them extracts of the husk or polishings. But he did not interpret his experiments correctly either. He thought that the The bulk of the experiments on scurvy in the early years of the twentieth polished rice contained a poison and the polishings contained a natural century was carried out by nutritionists who had contrived the vitamin antidote. Four years later another Dutchman correctly interpreted these hypothesis and the concept of deficiency diseases. They had already taken experiments, suggesting that beriberi in birds and men is caused by the lack scurvy under their wing as a typical dietary deficiency disease. They had of some vital substance in the polished rice that is present in the rice bran. even named its cause and cure, vitamin C, without knowing anything more definite than the fact that it was some vague factor in fresh vegetables and In 1905 and 1906, Pekelharing in Holland and Hopkins at Cambridge, fruits. England, repeated the old experiment of feeding rats and mice on purified diets and again found that they failed to grow and died young. But they While the nutritionists were busy with their rats, mice, guinea pigs, and went one step further and found that adding small amounts of milk, not vitamin theories, another important event took place in medicine. We will exceeding four percent of the diet, allowed the animals to grow and live. mention it briefly here because it happened at about this time, and we will Both investigators realized that there was something present in natural come back to it later to explain its significance to ascorbic acid and scurvy. foods that is vitally important to good nutrition. The concept of deficiency In 1908, the great English physician, Sir Archibald Garrod, presented a diseases (the idea that a disease could be caused by something lacking in remarkable series of papers in which he set forth new ideas on inherited the diet) was dawning. metabolic diseases, or as he stated it, “Inborn errors of metabolism.” These Two Norwegian workers, Holst and Frohlich, in 1907, were also are diseases due to the inherited lack of certain enzymes. This lack may investigating beriberi, which was common among the sailors of the cause a variety of genetic diseases depending upon which particular enzyme Norwegian fishing fleet. is missing. They were able to produce the disease in chickens and pigeons but they The fatality of these diseases depends upon the importance of the wanted another experimental animal, a mammal, to work with. They chose biochemical process controlled by the missing enzyme. It may vary from the guinea pig, and a fortunate choice it was for man and the science of relatively benign to rapidly fatal conditions. This was a revolutionary nutrition. After feeding the guinea pigs the beriberi-inducing diets, they concept for those days – a disease caused by a biochemical defect in one’s inheritance. 8. THE GENETIC APPROACH Now getting back to the main thread of our story, the nutritionists continued Although the search for our elusive molecule has ended, our story has not. their work with their new-found experimental animals and in the next Actually, the means for ascorbic acid’s unlimited synthetic production decades uncovered more information about our elusive molecule. provide us with a second beginning. We shall now see how the subsequent To study the chemistry of a substance such as ascorbic acid, it is necessary investigations of the following forty years got off to a wrong start which to concentrate it from the natural extracts, to isolate it in pure form, to hindered our understanding of this unique molecule and the thorough crystallize it, and to recrystallize it to make sure it is just one single exploitation of its vast therapeutic potentialities. To better understand the chemical compound. Only then can it be identified chemically, and its circumstances of this paradoxical situation, we will try to look into the molecular structure determined. Once the structure of the compound is mental climate of the most advanced investigators in this field in the early known, it is relatively easy to find ways to synthesize it. Comparison of the 1930s. A reader of the previous historical chapters would know vastly synthetic material with those of the original crystals will either confirm or more about ascorbic acid and its place in human evolution than anyone in deny whether the chemist’s tests and reasoning were correct. that era. The mechanisms of the natural synthesis of ascorbic acid by plants and animals were still unknown and their genetic significance was not even In the early 1920s scientists began concentrating the vitamin C factor and a gleam in any researcher’s eye. The important enzyme L-gulonolactone studying its behavior under various chemical treatments by means of oxidase was awaiting discovery in the far distant future and the importance quantitative animal assays. It was a long drawn-out procedures but it was of this and related enzyme systems were not even suspected. All the gradually becoming clear why the molecule vanished so easily. The real investigators had been brought up on the dogmatic tenets of the then thirty- tests, however, had to wait its isolation and crystallization in pure form. year-old vitamin-C theory. Scurvy was an avitaminosis (a dietary As scientists approached the home stretch of the search their pace deficiency disease) and this nutritional disturbance could be prevented or quickened and attracted more workers. There was a group at the Lister cured by ingesting minute amounts of this trace nutrient into the diet. Thus Institute in England and another in the United States; a Russian directed vitamin C was considered a trace food constituent found in certain group in France and later other groups formed. History has a way of foodstuffs and was not even remotely associated with the idea that it might playing tricks on the course of events. In the years before our elusive have been a product of man’s original metabolism. molecule was finally pinned down, there were a few close calls in the In the early and mid-1930s the status of scurvy had changed little from the attempts to isolate it in pure form which, for one reason or another, were time of Lind in 1753 when it was considered a food-related disease, except never successful. In the early 1920s a student worker at the University of that 20 years earlier someone had called the unknown substance a Wisconsin, studying the biochemistry of oats, isolated a crude crystalline “vitamine.” As time rolled one and more facts were gathered, it seemed that fraction which may have been our elusive material. The work was carried “vitamin C” was not behaving like a typical vitamin. For nearly all animals no further because the dean refused a research grant of a few hundred it was not even a “vitamin” because of its widespread manufacture in their dollars which was required to pay for animal assays of these crude crystals. own bodies; they never got scurvy no matter how little vitamin C was in In 1925, two U.S. Army workers at Edgewood Arsenal were on the verge of their food. Out of the thousands of different animals existing in Nature obtaining crystals of the antiscorbutic substance when they were transferred only three (man, monkeys and guinea pigs) were known to need vitamin C to different stations; their work was never completed. Bezssonov, the in their foodstuff. The effective dosages of vitamin C were also Russian worker in France, may have isolated antiscorbutic crystals from considerably higher than those for the other known vitamins. As the cabbage juice in 1925, but for some unknown reason these crystals were chemical and enzymatic mechanisms of how plants and animals make their never thoroughly investigated. own vitamin C became known, the terms “vitamin C” and “ascorbic acid” In 1928, Albert Szent-Gyorgyi, working at Cambridge, England, on a became more and more synonymous. In the field of biochemical genetics, biochemical problem unrelated to scurvy or vitamin C, reported that he has great advances were being made in understanding the mechanisms of isolated crystals of a new sugarlike substance with very unusual chemical heredity. A vast amount of clinical work was reported on the use of properties from the adrenal gland of the ox. He called the substance ascorbic acid in the treatment of all known diseases, much without “hexuronic acid.” Similar crystals were isolated from oranges and spectacular success except in the case of scurvy. These developments and cabbages. While these crystals were isolated in connection with another others, covering a quarter of a century, were instrumental in shaping the biochemical problem, Szent-Gyorgyi noted their similarity to the chemical author’s genetic concepts of the human need for ascorbic acid. The vitamin reaction of vitamin C and suspected there was some connection. He made C hypothesis never attempted to explain why we were susceptible to scurvy, arrangements to have the crystals tested by animal assay but before he could only how we got it. This hypothesis no longer served the new accumulation obtain enough crystals he left England and the matter was left in abeyance. of facts, and clearly a new approach was required. However, up until 1966, It was not until 1931, after he had resettled in Hungary, that he was able to the vitamin C hypothesis was an unquestioned part of published medical pick up the threads and carry out the necessary tests which proved dogma. hexuronic acid to be vitamin C. In that year, a student of Hungarian For the development of these new concepts we have to return to Sir descent, J.L. Svirbely, who had worked with the American team of vitamin Archibald Garrod, mentioned in the last chapter, who in 1908 introduced C researchers at the University of Pittsburgh under Charles Glenn King, the concept of the inherited enzyme disease into medicine. At the time, this returned to Hungary and joined forces with Szent-Gyorgyi to work on the was a revolutionary way of explaining the cause of disease in man. These problem. The years 1932 and 1933 were very fruitful and saw many genetic diseases are caused by the inherited lack or inactivity of a certain published reports by American, Hungarian, English, and other workers. All specific enzyme. The inability of the enzyme to function normally prevents this research showed that hexuronic acid was indeed our elusive molecule, the body from carrying out the biochemical process involved. This may and it was soon renamed “ascorbic acid.” cause toxic by-products to accumulate or abnormal biochemical pathways With the pure crystals of ascorbic acid available, its chemical structure was to develop which bring on the symptoms of the genetic disease. As quickly determined and methods for its synthetic production from the mentioned earlier, the diseases range from the relatively harmless to those sugars were devised. The development of these syntheses permitted that are rapidly fatal. The reader will remember that the body contains unlimited production of ascorbic acid at a low price and provided a thousands of enzymes for carrying out the living process and the absence of practical solution to a problem that had always beleaguered man – but of any one can bring on an “inborn error of metabolism.” Since each of the which he was still unaware. body’s enzymes is synthesized from a single gene in the chromosome, a slight mutation of the gene can cause the loss of an enzyme and thus cause a Thus our elusive molecule was finally pinned down and revealed. The genetic disease. search had ended. The importance of this work was recognized in 1937 by the award of two Nobel Prizes: one to Szent-Gyorgyi for his biochemical Sir Archibald, in his original 1908 papers, described four genetic diseases discoveries and the other to the English chemist, Sir Walter Haworth, for but the list has now grown and new ones are constantly being reported. He his research on the chemical structure and synthesis of ascorbic acid. reported on albinism, alkaptonuria, cystinuria and pentosuria, all due to the lack of a particular enzyme in the afflicted individual’s biochemical 9. SOME EFFECTS OF ASCORBIC ACID inheritance. At this point it is best to discuss briefly some of the effects of ascorbic acid Albinism, a relatively harmless condition, is due to the lack of an enzyme on various important bodily functions. This will give the reader a better used in the production of the black skin pigment, melanin. Alkaptonuria insight and background for the later chapters. Ascorbic acid is involved in and cystinuria are both diseases of protein metabolism in which the missing so many vital biochemical processes and is so important in daily living that, enzyme causes an accumulation of intermediate protein digention products, after forty years of research, we still have no clear idea of all the ways in which causes changes in the urine and other parts of the body. which it works. Alkaptonuria is relatively benign until late in life when it produces a severe Throughout the evolution of the vertebrates, including the mammals, Nature type of arthritic condition. has used ascorbic acid to maintain physiological homeostasis. In simple Cystinuria induces the formation of kidney and bladder stones, while the nontechnical terms, this means that when stressful situations arose which relatively rare and harmless pentosuria causes pentose, a sugar, to appear in disturbed the biochemical equilibrium of the animal, ascorbic acid was the urine and may be confused with diabetes. produced in increased quantities to get things running normal again. The amount of ascorbic acid produced is related to the severity of the stresses Like many other great discoveries in medicine, Garrod’s work was almost and if enough was produced soon enough, then the animal was able to ignored for a generation. In fact, an examination of the major genetics survive the bad biochemical effects of the stresses. If, however, the enzyme textbooks in use in 1940 fails to reveal any mention of alkaptonuria, system for producing ascorbic acid was overwhelmed or poisoned by the described by Garrod thirty-two years earlier. Time has corrected this stresses and too little ascorbic acid was produced, then the animal oversight and the importance of Garrod’s pioneering work is now succumbed. Man, unable to produce his own ascorbic acid, could not take acknowledged by all. advantage of this natural protective process. Instead stresses only further Two more recent genetic diseases, now much in the news, will be briefly depleted his low stores of this vital metabolite. Now he can easily duplicate mentioned: galactosemia, which afflicts infants, is caused by a missing this time-tested defensive mechanism by reaching for the bottle of ascorbic enzyme, galactose-1-phosphate-uridyltransferase, (all enzyme names end acid and swallowing additional quantities whenever he is subjected to with “ase”) that prevents babies from properly digesting the sugar in milk. biochemical stresses. In duplicating this normal process for combating Unless they are promptly taken off a milk diet, they will sicken and may die. stresses, man has one great advantage over the other mammals – he can get Those that survive will be stunted in growth, may develop cataracts, and an unlimited supply of ascorbic acid without being dependent upon an may be mentally retarded. The other genetic disease, phenylketonuria (or enzyme system which may not produce enough, quickly enough. PKU), is another disease of infants and is caused by the inherited lack of the All man needs to know is how much to take. enzyme, phenylalanine hydroxylase, producing a profound disturbance of protein digestion. Unless the victims are placed on special low-protein One of the outstanding attributes of ascorbic acid is its lack of toxicity even diets, irreversible brain damage can occur as well as mental retardation and when given in large doses over long periods of time. This has been other nervous disorders. recognized since the 1930s, and ascorbic acid can be rated as one of the least toxic substances known of comparable physiological activity. It can Figure 3 be administered in huge doses, intravenously, without registering any Sugar Metabolism and Conversion to Vitamin C serious side effects. Now back to ascorbic acid. In mammals, ascorbic acid is produced in the Because of human variability and because the human organism has been liver from blood glucose by the stepwise reactions shown in Figure 3. Each exposed to such low levels of this essential substance for so long, some step, except the last, is controlled by a specific enzyme. In the last step, the usually transient side effects may occur in a small percentage of 2-keto-L-gulonolactone, once formed, is automatically converted into hypersensitive individuals. ascorbic acid. No enzyme is required. On the right side of the diagram, the This may be evidenced as diarrhea or rashes which clear up on lowering step of transforming L-gulonolactone into 2-keto-L-gulonolactone is the dosage. In many cases it is possible to avoid these reactions by building catalyzed by the enzyme L-gulonolactone oxidase. This is the critical up to the desired dosage gradually, which permits the body to become enzyme for humans who, because they carry a defective gene, cannot accustomed to these essentially normal mammalian levels. Taking the produce an active enzyme. This is the gene that mutated in a primate ascorbic acid with food or before meals often helps. ancestor of ours millions of years ago. It is this step that is blocked in man and prevents him from producing large amounts of ascorbic acid from Chemically, ascorbic acid is a rather simple carbohydrate related to the glucose in the liver. blood sugar, glucose (see Figure 1, page __). Unlike glucose, it contains an unusual, highly reactive combination of molecules called the “ene-diol Here we have the classic conditions for a genetic, missing-enzyme disease, group.” The presence of this group confers upon the ascorbic acid molecule and yet for years these simple facts have been ignored and scurvy has certain unique biochemical characteristics which amy explain its vital continued to be regarded as avitaminosis. In 1966, this author published importance in the living process. It transforms a relatively inactive sugar the paper “On the Genetic Etiology of Scurvy,” in which the history and into a highly reactive, labile, and reversible carbohydrate derivative which pertinent facts were reviewed and it was pointed out that in scurvy we were readily donates or accepts electrons from its surrounding medium. This is dealing with a genetic, liver-enzyme disease and not simply a dietary know technically as an “oxidation-reduction system.” disturbance. Since it is the prerogative of the discoverer to name a new disease, the author called it “hypoascorbemia” because low levels of On a molecular basis, the whole living process is nothing more than an ascorbic acid in the blood are characteristic of this disease. orderly flow and transfer of electrons. Therefore, having an abundance of a substance like ascorbic acid present in living matter makes this orderly flow This genetic approach now provides a natural rationale for the use of large and transfer of electrons proceed with greater ease and facility. It acts amounts of ascorbic acid which served so well in the survival of the substantially like an oil for the machinery of life. This was discovered by mammals in the course of evolution. Its implications for health and well- Nature billions of years ago. Recent work indicates that this oxidation- being are vast because it furnishes the basis for the new unexplored fields of reduction system can form even more active free radicals which may preventive medicine and therapeutics (megascorbic prophylaxis and explain some of its unusual biological effects. megascorbic therapy). It is hoped that the publication of these new ways of using ascorbic acid will stimulate the flood of research similar to that which There are no large storage depots for ascorbic acid in the body and any occurred when ascorbic acid was discovered in the early 1930s. Let us see excess is rapidly excreted. When saturated, the whole body may only how long it will take to break down the “vitamin-barriers” of current contain 5 grams. orthodox medical dogma. This means that the body requires a continuous supply to replenish losses and depletions. The livers of nearly all mammals are constantly making and pouring ascorbic acid into their bloodstreams, but man’s liver is unable to particularly sensitive to the lethal action of ascorbic acid. do this. He needs a constant, large, outside supply to make up for this One of the body’s defenses against bacterial infections is the mobilization genetic defect. of white blood cells into the affected tissues. The white blood cells then When the different organs and tissues are analyzed, it is found that ascorbic devour and digest the invading bacteria. This process is known as acid concentrates in the organs and tissues with high metabolic activity; the phagocytosis and is controlled by ascorbic acid. The number of bacteria adrenal cortex, the pituitary gland, the brain, the ovaries, the eyes, and other that each white blood cell digests is directly related to the ascorbic acid vital tissues. Any form of biochemical stress or physical trauma will cause content of the blood. This is one of the reasons why a lack of ascorbic acid a precipitous drop in the ascorbic acid levels of the body in general, or in the body produces lowered resistance to infectious diseases. locally in the affected organs or tissues. In animals biochemically equipped Ascorbic acid is also a potent and nonspecific virucide. It has the power to to produce their own ascorbic acid, any stressful situation causes them to inactivate and destroy the infectivity of a wide variety of disease-producing synthesize more and greater amounts to replace that destroyed or utilized in viruses including poliomyelitis, herpes, vaccinia, foot-and-mouth disease, combating the stresses. and rabies. It only does this, however, at relatively high doses, not a One of the most important biochemical functions of ascorbic acid in the “vitamin” level. body’s chemistry is the synthesis, formation, and maintenance of a protein- There is a relationship between ascorbic acid and the production and like substance called collagen. Collagen cannot be formed without ascorbic maintenance in the body of the adrenal cortical hormones. The adrenal acid, which is absolutely essential to collagen production by the body. gland, where this hormone is produced, also happens to be the tissue where Collagen is the body’s most important structural substance. It is the ground the highest concentration of ascorbic acid is found. substance, or cement, that supports and holds the tissues and organs together. It is the substance in the bones that provides the toughness and In 1969 it was reported that laboratory tests conducted at the National flexibility and prevents brittleness. Without it the body would just Cancer Institute showed that ascorbic acid was lethal to certain cancer cells disintegrate or dissolve away. It comprises about one-third of the body’s and harmless to normal tissue. This might be the long awaited total weight of protein and is the most extensive tissue system. It is the breakthrough in cancer therapy. Intensive study and research should substance that strengthens the arteries and veins, supports the muscles, immediately be concentrated to investigate these possibilities. toughens the ligaments and bones, supplies the scar tissue for healing wounds and keeps the youthful skin tissues soft, firm, supple and wrinkle This has been a brief and incomplete summary of ascorbic acid’s many free. When ascorbic acid is lacking, it is the disturbance in collagen biochemical functions and of its vital importance in keeping the body in formation that causes the fearful effects of scurvy – the brittle bones that good operating condition. Even this incomplete review should not only fracture on the slightest impact, the weakened arteries that rupture and give the reader an idea of the many important functions of ascorbic acid, but hemorrhage, the incapacitating muscle weakness, the affected joints that are also leave the very distinct impression that ascorbic acid can be of much too painful to move, the teeth that fall out, and the wounds and sores that greater use to man than as a mere prevention of clinical symptoms of never heal. Sub-optimal amounts of ascorbic acid over prolonged periods scurvy. during the early and middle years, by its effect of producing poor quality collagen, may be the factor in later life that causes the high incidence of 10. “ CORRECTING” NATURE arthritis and joint diseases, broken hips, the heart and vascular diseases that No one would have any difficulty recognizing the violent, extreme cause sudden death, and the strokes that bring on senility. Collagen is symptoms of totally “uncorrected” hypoascorbemia – the clinical scurvy; intimately connected with the entire aging process. but the milder forms, from which most people suffer, are difficult to detect. Ascorbic acid has a marked activating effect on many bodily enzymes and Chronic hypoascorbemia, or as it was previously called, “subclinical makes the processes controlled by these enzymes proceed at a more scurvy,” is relatively symptom-free and can only be diagnosed by clinical or favorable rate. It is very important in nutrition, the digestion of food and chemical testing, or by difficult long-term observations. Acute scurvy in the biochemistry of the body’s utilization of carbohydrates, proteins, and the well-developed nations is, nowadays, not a common disease for two fats. In carbohydrate metabolism it has a pronounced activating effect on reasons. insulin. It is essential to the proper functioning of the nervous system. First, the daily amounts of ascorbic acid needed to protect against the Brain chemistry is dependent on the maintenance of proper levels of symptoms of clinical scurvy are very small and, second, the improvements ascorbic acid and high levels are essential in treating nervous and mental in food preservation and distribution make it easy to obtain these small disorders, as we shall see in a later chapter. amounts in foods available the year round. This is not the case, however, Ascorbic acid is a potent detoxicant which counteracts and neutralizes the for chronic hypoascorbemia. Anyone who depends solely on foodstuffs for harmful effects of many poisons in the body. It will combat various ascorbic acid cannot expect “full correction” of hypoascorbemia. The more inorganic poisons, such as mercury and arsenic, and it neutralizes the bad stress that such an individual is under, the higher would be the deficit. It is reactions of many organic poisons, drugs, and bacterial and animal toxins. the lack of recognition of the distinction between acute scurvy and chronic Ascorbic acid detoxifies carbon monoxide, sulfur dioxide, and carcinogens, hypoascorbemia, and the narrow aims of the “vitamin” theory, that have so it is the only immediate protection we have against the bad effects of air given a false sense of security, for the past sixty years, as to the adequacy of pollution and smoking. It has also been shown that ascorbic acid increases foodstuffs to fully supply the body’s needs for ascorbic acid. the therapeutic effect of different drugs and medicines by making them Hypoascorbemia can be “corrected” by supplying the individual with more effective. Thus, less of a drug is required if it is taken in combination ascorbic acid in the amounts the liver would be making and supplying to the with large amounts of ascorbic acid. Diabetics could reduce their insulin body if the enzyme were not missing. How, then, can we determine the requirements if this were practiced. Even an aspirin should be accompanied amounts of ascorbic acid the human liver would be producing by an enzyme by a large does of ascorbic acid to heighten its analgesic effect and lessen that is not there? The solution to this question may not be as difficult as it its toxic action on the body. may seem at first glance. If the requirements for ascorbic acid in man are Ascorbic acid in large doses is a good nontoxic diuretic. A diuretic is a assumed to be similar to those of other, closely related mammals, then, by substance that stimulates the excretion of urine. Thus, ascorbic acid at measuring the amounts of ascorbic acid produced by other mammals, we proper dosage levels will drain waterlogged tissues and reduce accumulated should be able to get a pretty good estimate of what man would be making, water in the body in heart and kidney diseases. had he the complete synthetic enzyme system. The antiseptic and bactericidal qualities of ascorbic acid have long been When we look for this very important data in the literature, it is amazing known. how little we find. The only information available is on the rat. No one has bothered to determine the amounts of ascorbic acid the larger mammals At relatively low levels it will inhibit the growth of bacteria and at slightly such as the pig, dog, or horse are capable of producing. higher amounts it will kill them. The bacteria causing tuberculosis is