Zinc; Interferon and RNA-DNA Complex; Zinc and Health
Contents in in this issue:
- “Zinc, a Vital Micronutrient” (includes Beatrice Trum Hunter’s book review of Zinc Metabolism by Ananda S. Prasad, PhD),
- “Interferon and the RNA-DNA Complex,”
- “Zinc and Health.”
The following is a transcription of the October 1967 issue of Dr. Royal Lee’s Applied Trophology newsletter, originally published by Standard Process Laboratories.
Zinc, a Vital Micronutrient
Zinc is a necessary component of several enzyme systems that regulate various metabolic activities within plants and animals. A biological report by B.L. Vallee and J.G. Gibson in J. Biol. Chem., pp. 176, 445 (1948), and subsequent studies by Vallee and several other associates reported in Physiol. Rev., pp. 39, 443 (1950), J. Biol. Chem., pp. 195, 531 (1952), and J. Amer. Med. Assoc., Vol. 162, No. 11, p.1053 (1956), stimulated further interest in mineral metabolism. Through these and later studies we have learned much in regard to the significance of zinc in various tissues of the body.
The early recognition that carbonic anhydrase is a zinc enzyme, with the mineral becoming an integral part of the enzyme molecule, led to further interesting scientific facts. The spade work of Vallee et al. has led to the isolation of the alcohol dehydrogenases, lactic dehydrogenases, glutamic acid dehydrogenase and carboxyl peptidase as zinc-associated enzymes.
The experiments revealed that zinc ions increased the activity of many enzymes and important biological functions regarding cellular oxidation and, we presume, other important aspects of metabolism.
Zinc has been found to be an important constituent of blood plasma. Although leukocytes contain only about 3 percent of the zinc in whole blood, the individual normal leukocyte is rich in zinc and “probably contains more zinc than does any other cell in the body.” However, Vallee and associates found that the zinc contents of leukemic leukocytes were from 10 to 40 percent less than normal values and observed that “one characteristic of the blood dyscrasias known as leukemia is an inability of the leukocytes to attain a normal zinc content.” H.P. Wolfe reported in Lin. Woch., pp. 34, 409 (1956) relatively low values for the serum zinc of leukemic patients. More recently we learn from Med. World News, March 3, p. 9 (1967) that “zinc content of leukocytes is found to be low in certain types of cancers of the larynx, tongue and tonsils as shown by test on the enzymes systems of these tissues.”
The early importance of zinc in human nutrition was established by Gilbert in Mineral Nutrition, Oklahoma University Press, 1943, when he stated, “The human body contains about half as much zinc as it does iron.” In his experiments he found it to be of great importance in the functioning of the pancreas. Later it also was found to be of importance in the male genital tract, especially the prostate gland, the eye, and other organs. The pancreas, he determined, needed zinc for the normal synthesis of insulin. “Insulin being a carrier of organic zinc, the pancreas gland necessarily has a content of zinc.”
Information as to the high importance of this micronutrient in the physiological processes of both plant and animal life is constantly increasing. In plant life zinc deficiency has caused cellular disturbances leading to structural abnormalities in seeds, leaves, stems, and roots.
In mammalian life we find:
- Zinc deficiency causes birth defects in the rat. A diet containing only 9 parts per million of zinc provided normal growth in the female rat but caused congenital malformations in nearly every offspring. (Nutrition Reviews, May 1967.)
- Zinc deficiency causes physical disturbances. Retardation of growth and lack of sexual maturation in children in the tropics and subtropics was found to be due to zinc deficiency. Iron deficiency often accompanies zinc deficiency but does not cause these particular disorders. (American Journal of Clinical Nutrition, May 1967.)
We continue “Zinc, a Micronutrient” with the complete reprint of the review of a recently published book entitled Zinc Metabolism, compiled and edited by Ananda S. Prasad, PhD (Charles C. Thomas Pub. Co., Springfield, IL., USA, $16.75.)
The subject of zinc in terms of farming has long been of interest to this reviewer, after having heard a dramatic incident about the profound influence of this micronutrient. A Florida citrus grower was despondent because his sickly trees failed to bear fruit. He tacked up a “For Sale” sign on his trees that bordered the highway, hoping to attract a buyer. Due to the poor appearance of the grove, there were no buyers. But in the following season, there was an astonishing sight. Each tree bearing the “For Sale” sign blossomed forth with magnificent flowers and fruit. The grove had been zinc deficient. The infinitesimal amount of zinc present in the zinc-coated nails that had been used for tacking up the signs was enough to spell the difference between crop failure and success. Armed with this knowledge, the grove was restored to vigor.
The need for zinc as an essential for plants and animals was demonstrated nearly a century ago. Zinc deficiency is becoming recognized worldwide and considered only secondary to nitrogen deficiency among soil fertility problems. At present, of 17 western states (and Hawaii) in U.S.A. all but Nevada show zinc deficiency in at least one crop. Some 32 states throughout U.S.A. show zinc deficiency in one or more crops. It occurs in severe form in at least four states in Australia; two districts in New Zealand; in broad areas across Central and South Africa, Brazil, and Western Europe (in fruit trees and grapes); in south central Asia; in U.S.S.R. (corn); and in the Netherlands (grass).
Zinc deficiency is most prevalent in neutral to alkaline soils, which contain lime in the profile. It is also common on acidic leached and on very acidic peat soils. It is rare on cool temperate podzolic soils and deep black soils of true prairies. All soils, however, are more apt to produce crops with zinc deficiency symptoms when they are pushed to high levels of production. Experimentally, attempts have failed to produce zinc deficiency by heavy applications of manure, urine, or soil compaction.
Zinc deficiency, according to the participants in the symposium on Zinc Metabolism, has become more prevalent since World War II due to changes in soil and crop management. Some crucial aspects are mentioned. There is less recycling of the plant-available forms of zinc on the farm since the tractor has been substituted for the horse. Fewer cattle are fed from farm crops, and more of the grain and forage as hay and ensilage are sold off the farm to a commercial feeder. Hence, the feeder who disposes of manure off the farm does not return it to the soil that produced it. Dairying and poultry operations have become concentrated away from the farm where the feed is grown, and this breaks the zinc cycle.
The use of commercial fertilizers has been responsible for zinc deficient soils. These fertilizers have become “purer.” Most of the nitrogen now comes from synthetic ammonia plants and contains no zinc. More of the phosphates presently comes from electric-furnace phosphoric acid, low in zinc. Many superphosphates once sold in the Western U.S.A. contained much zinc, largely from zinc-contaminated sulfuric acid used in their manufacture.
The western United States produced superphosphates that contained five times more zinc than eastern ones. Fillers added to the concentrated fertilizers now marketed have less zinc as contaminant than formerly. Zinc deficiency may be induced by the overuse of phosphates, and so may over-liming and acid soil, since zinc and calcium are antagonistic. With the demands for higher yield of crops, produced in sequence of four crops with nitrogen fertilizers, heavy demands are made on the available zinc supply. Experiments show that doubling the per acre yield doubles the total zinc removed.
Man’s need for zinc has been demonstrated relatively recently. Signs of zinc deficiency were suspected as recently as 1961 and only pinpointed in 1963, in adult males in Iran and Egypt. The subjects suffered from severe dwarfism and marked underdevelopment of gonads. Zinc supplementation increased their growth and gonadal development.
Currently, facts are not well established, but it is believed that zinc in the cells controls physiological processes through its associations with enzymes. Zinc is found throughout the human body. The hair contains the greatest concentration. Next comes the prostate gland, and then, in descending order: kidney, liver, muscle, aorta, heart, pancreas, spleen, ovary, testes, lung, brain, and adrenal.
Zinc Metabolism attempts to survey the subject from the points of view of this metal’s nutritional, biochemical, and clinical significance to living organisms. The book is a symposium of experts writing from different scientific disciplines. It forms a compilation of impressive proportions of present knowledge on the subject of this vital micronutrient.
—Beatrice Trum Hunter, reported in Mother Earth—Journal of the Soil Association, April 1967
In part from “The Trace Elements,” Food: The Yearbook of Agriculture 1959 (p. 129):
“The function of zinc appears to be to hold the molecules diphosphopyridine nucleotide and triphosphopyridine nucleotide (derivatives of the vitamin niacin) in proper orientation for reactions involving the transfer of hydrogen atoms and electrons between these nucleotides and a number of other organic molecules. The zinc is thought to be attached to the surface of the enzyme, and the nucleotide attached in turn to the zinc. The metal in this case may be envisioned as important in properly modifying the surface of the enzyme” (p. 125).
“The emphasis in research has begun to shift. The function of trace elements in the action of enzymes has become one of the central problems in biochemistry today, and the nutritional research with respect to the trace elements now is motivated more by the desire to understand these constituents of living things than by economic necessity.
“We cannot foresee what practical applications will be made of this more fundamental research. It is important to remember that life is a delicate balance of a seemingly infinite number of competing chemical and physiological processes. The trace elements are obviously of great importance to these processes and to that balance.
“Health, we are beginning to realize, is more than the absence of disease. It is, rather, the ideal in which the perfect balance of the processes of life is achieved. The study of trace elements and their functions is therefore the study of health.”
As reported by Kenneth J. Monty and William D. Mc Elroy (Dept. of Biology, John Hopkins University and the McCollum-Pratt Institute) in “The Trace Elements,” Food: The Yearbook of Agriculture 1959.[Ed. note: “The Trace Elements” is mistakenly cited as “The Trace Minerals” in the source material. We have corrected the error.]
Interferon and the RNA-DNA Complex
Over ten years ago Dr. Alick lsaacs, a British research scientist, and his colleagues discovered a protective protein substance in living body tissue. This cellular substance seemed to protect the cell from, or at least interfere with, the production of viruses. It was therefore called interferon.
Now a new research team led by Dr. R. Hilleman, director of virus and cell biology research at the Merck Institute for Therapeutic Research in Pennsylvania, has discovered that this protective tissue (which they continue to call interferon) can be produced by the body itself. They found this protection involved a broad range of virus so they believe it could have a major public health significance.
The living cells of every plant and animal are organized and run by its tiny nucleus. The key chemicals of the nucleus are the nucleic acids DNA and RNA. We know that in the nucleus of a healthy cell the DNA molecules carry the blueprints for the busy normal life processes. They issue orders that are obeyed and handed on by RNA molecules. Usually RNA molecules are found in a single strand. Virus infection may upset this orderly procedure. According to biologists who have studied virus under the electron microscope, it takes at least a million of these miniature organisms to measure an inch. Because of lack of knowledge they are not classified as either plants or animals at this time.
In suitable surroundings they move and multiply, and like living cells they can mutate or alter their structure. To add to the confusion, in the study of viruses they also are found to be composed of DNA-RNA molecules. With this newer knowledge it is easier to understand how a miniscule virus can invade the nucleus of a cell and interfere with its normal processes—in fact, in some instances, causing the DNA molecules in the nucleus to neglect their own duties and to produce copies of the virus.
The misunderstanding of this piratical biological action has in the past led a few chemists to proclaim that the nucleic acids may be carcinogenic. Newer biological investigation of cellular life, viruses, and the nucleic acids in their relation to each other have completely nullified that theory. In fact, Dr. Hilleman’s researchers have found that the RNA in viruses may occur in double strands rather than in single strands as usually found in nucleoli RNA. He advises that it is only in the double-stranded form that RNA will trigger the production of interferon. Again, we find that nature has furnished the necessary protective material within the body. When RNA in the virus is transformed into interferon it apparently causes the virus to lose its identity.
This new knowledge of interferon production has been used to protect mice against two viruses that would otherwise have been fatal. Interferon research is reported in three scientific papers to be published in the Proceedings of the National Academy of Sciences.
Zinc and Health
In a recent report of research done by Dr. William Strain and Charles Rob at the University of Rochester Medical School, Rochester, NY, earlier evidence has been confirmed. Zinc was found to be essential to human health through increasing life expectancy, stimulating growth, accelerating healing, and involvement in sexual development. Dr. Strain believes that zinc may be effective in the treatment of atherosclerosis, alcoholism, and heart disease.
A report in The Lancet, January 21, 1967, indicates that zinc is needed for optimal healing in man and confirms clinically some of Dr. Strain’s research evidence. Wounds of several airmen, surgical patients treated by Medical Officers Walter Pories and John Henzel of Wright-Patterson Air Force Base Hospital, Dayton, Ohio, healed over 40 percent sooner than those of fellow patients not receiving oral doses of a zinc supplement. Lack of side-effects and the benefit of rapid healing has convinced Major Pories and associates concerned that zinc deficiency may be very common in man.
A deficiency of microminerals together within sufficient protein (amino acids) and loss of vitamins (all cooperating constituents of enzymes) inhibits enzyme activity, thereby causing imbalances by deaccelerating necessary body chemical reactions. “The trace elements are obviously of great importance to these processes and to that balance.”