Against Disease

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Coming in the next issue: THE EVOLUTION OF MAN

OUR ANCESTRAL PRIMATE If we come forward to a time some 55 to 65 million years ago we will find that the warm-blooded vertebrates are the dominant animals, and they are getting ready to evolve into forms that are familiar to us. Life has come a long way since it discovered how to make ascorbic acid. In the warmer areas the vegetation is dense and the ancestors of our present-day primates -- the monkeys,apes, and man -- shared the forests and treetops with the innumerable birds. At about this time something very serious happened to a common ancestor of ours, the animal who would be a progenitor of some of the present primates. This animal suffered a mutation that eliminated an important enzyme from its biochemical makeup. The lack of this enzyme could have proved deadly to the species and we would not be here to read about it except for a fortuitous combination of circumstances. Perhaps we should digress here and review some facts of mammalian biochemistry as related to this potentially lethal genetic accident. It will not be difficult, and it will help in understanding the thesis of this book. All familiar animals are built from billions of cells. Masses of cells form the different tissues, the tissues form organs, and the whole animal is a collection of organs. The cell is the ultimate unit of life. Each cell has a cell membrane, which separates it from neighboring cells and encloses a jellylike mass of living stuff. Floating in this living matter is the nucleus, which is something like another, smaller cell within the cell. This nucleus contains the reproducing macromolecule called desoxyribonucleic acid (DNA). DNA is the biochemical basis of heredity and determines whether the growing cells will develop into an oak tree, a fish, a man or whatever. This molecule is a long, thin, double-stranded spiral containing linear sequences of four different basic unit molecules. The sequence of the four unit molecules as they are arranged on this spiral is the code that forms the hereditary blueprint of the organism. When a cell divides, this double-stranded molecule separates into two single strands and each daughter cell receives one. in the daughter cell, the single strand reproduces an exact copy of itself to again form the double strand and in this way each cell contains a copy of the hereditary pattern of the organism. These long threadlike molecules are coiled and form bodies in the nucleus that were called chromosomes by early microscopists because they avidly absorbed dyes and stains and thus became readily visible in preparations viewed microscopically. These microscopitst suspected that these bodies were in some way connected with the process of inheritance but did not know the exact mechanisms. Certain limited sections of these long, spiral molecules, which direct or control a single property such as the synthesis of a single enzyme, are called genes. A chromosome may be made up of thousands of genes. The exact order of the four different unit molecules in a gene determines, say, the protein structure of an enzyme. If only one of these unit molecules is out of place or transposed among the thousands in a gene sequence, the protein structure of the enzyme will be modified and its enzymatic activity may be changed or destroyed. Such a change in the sequence of a DNA molecule is called a mutation. These mutations can be produced experimentally by means of various chemicals and by radiations such as X rays, ultraviolet rays, or gamma rays. Cosmic rays, in nature, are not doubt a factor in inducing mutations. It is on these mutations that Nature has depended to produce changes in evolving organisms. If the mutation is favorable and gives the plant or animal an advantage in survival, it is transmitted to its descendants. If it is unfavorable and produces death before reproduction takes place, the mutation dies out with the mutated individual and is regarded as a lethal mutation. Some unfavorable mutations which are serious enough to be lethal, but which the mutated animal survives, are called conditional lethal mutations. This type of mutation struck a primitive monkey that was the ancestor of man and some of our present-day primates. In nearly all the mammals, ascorbic acid is manufactured in the liver from the blood sugar, glucose. The conversion proceeds stepwise, each step being controlled by a different enzyme. The mutation that occurred in our ancestral monkey destroyed his ability to manufacture the last enzyme in this series -- L-gulonolactone oxidase. This prevented his liver from converting L-gulonolactone into ascorbic acid, which was needed to carry out the various biochemical processes of life. The lack of this enzyme made this animal susceptible to the deadly disease, scurvy. To this day, millions of years later, all the descendants of this mutated animal, including man, have the intermediate enzymes but lack the last one. And that is why man cannot make ascorbic acid in his liver. This was a serious mutation because organisms without ascorbic acid do not last very long. However, by a fortuitous combination of circumstances, the animal survived. First of all, the mutated animal was living in a tropical or semitropical environment where fresh vegetation, insects, and small animals were available the year round as a food supply. All these are good dietary sources of ascorbic acid. Secondly, the amount of ascorbic acid needed for mere survival is low and could be met from these available sources of food. This is not to say that this animal was getting as much ascorbic acid from its food as it would have produced in its own body if it had not mutated. While the amount may not have been optimal, it was sufficient to ward off death from scurvy. Under these ideal conditions the mutation was not 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 Garden of Eden, and became "civilized" that they -- we -- ran into trouble. This defective gene has been transmitted for millions of years right up to the present-day primates. This makes man and a few other primates unique among the present-day mammals. Nearly all other mammals manufacture ascorbic acid in their livers in amounts sufficient to satisfy their physiological requirements. This had great survival value for these mammals, who, when subjected to stress, were able to produce much larger amounts of ascorbic acid to counteract adverse biochemical effects. And there was plenty of stress for an animal living in the wild, competing for scarce food, and trying to avoid becoming a choice morsel for some other predator. To the best of our knowledge, only two other non-primate mammals have suffered a similar mutation and have survived. How many others may have similarly mutated and died off, we shall never know. The guinea pig 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-eating bat (Pteropus medius) from India. The only other vertebrates that are known to harbor this defective gene are certain passeriforme birds. Because of this missing or defective gene, man, some of the other primates, the guinea pig, and a bat will develop and die of scurvy if deprived of an outside source of ascorbic acid. A guinea pig, for example, will die a horrible death within two weeks if totally deprived of ascorbic acid in its diet.