Mysteries of Ribonucleic Acid; Cholesterol (Editorial)
Contents in this issue:
- “The Mysteries of Ribonucleic Acid,”
- “Cholesterol (Editorial from Clinical Physiology).”
The following is a transcription of the March 1964 issue of Dr. Royal Lee’s Applied Trophology newsletter, originally published by Standard Process Laboratories.
The Mysteries of Ribonucleic Acid
Much has been discussed in the past few months about ribonucleic acid (RNA) and desoxyribonucleic acid (DNA). These appear to be the nucleic acids that are responsible for cell self-duplication. Thorell comments that the content of ribonucleic acid in the cytoplasm is an index of metabolism and also of the protein synthesizing capacity of the system.
Let us review a few facts about nucleic acids and nucleoprotein metabolism:
- Desoxyribonucleic acid is exclusively found in the nucleus, probably in the chromatin;
- Ribonucleic acid is found both at the nuclear wall, where it is capable of being synthesized, and in certain basophilic cytoplasmic granules;
- It is the ribonucleic acid fraction of the nucleoprotein that is a growth promoter when added to tissue in vitro;
- An increase in the cytoplasmic content of ribonucleic acid is associated with protein synthesis and cell division.
Fisher demonstrated that the nonspecific growth-promoting properties of beef embryo nucleoproteins are primarily due to the ribonucleic acid fraction rather than the desoxyribose fraction. It is now widely believed that one fraction of the ribonucleic acid of a cell, the “messenger RNA,” is responsible for the transmission of genetic information from the desoxyribonucleic acid of the nucleus to the cytoplasm. This “messenger RNA” has been identified and differentiated from the total RNA.1
Carnegie Institution scientists in Washington, DC, have now developed an elegant method for comparing directly the genetic material of different species. The technique developed by Drs. Ellis T. Bolton and Brian J. McCarthy, of the institute’s Department of Terrestrial Magnetism, is based on a procedure originated by Dr. Saul Spiegelman at the University of Illinois. With it, the Carnegie investigators can compare both desoxyribonucleic acid (DNA), the nuclear material whose linked helices carry the hereditary information, and the messenger ribonucleic acid (RNA) that transports the information to the cell cytoplasm.
The Carnegie researchers are applying the technique to other biological problems. Dr. McCarthy, for example, has used it to study DNA and messenger RNA in different tissues of a single individual, including the brain, liver, kidney, spleen, and thymus. He finds that while DNA is alike in all the tissues, different types of RNA are manufactured by different parts of the animal’s DNA molecule. Thus, there is an intimate relationship to the type of cell produced and ribonucleic acid.2
Davidson remarks that the phospholipid-ribonucleoprotein particles of the cytoplasm lend themselves admirably as organs of protein synthesis. Even more significant is his comment: “It appears probably, therefore, that the phospholipin-ribonucleoprotein macromolecules constitute some of the fundamental units out of which living matter is built.”
A study performed in Russia by Z.A. Ryabinina to show the correlation between growth, DNA, RNA, and protein intake indicated that the protein nutrition (or at least some nutrient which is found in protein foods) is necessary for optimal synthesis of DNA and RNA on an intracellular basis. On a protein starvation diet, growth was retarded, follicular differentiation delayed, and intensification of follicular atresia at intermediate stages of follicular development led to a cessation of sexual development in immature rats and to a cessation of the estrus cycle in mature females. The amounts of RNA in both nucleoli and cytoplasms were reduced, but RNA did not completely disappear. DNA granules were larger and mainly concentrated about the nucleoli. The RNA was absent in the cytoplasm of the generative organs that had ceased to function, and the DNA was noticeably reduced.3
Dr. Holger Hyden, of the University of Goteborg, Sweden, reported qualitative changes of RNA in the neuroglia and the neuron in Parkinson’s disease. Interestingly enough, the amount of RNA changes in the neuroglia remained constant regardless if the patient was severely ill or only had mild symptoms. However, the change in RNA in the neuron or actual nerve cell corresponded to the severity of the condition. It should be noted that the RNA components were changed in the most bizarre way in every case.4
Memory Improved with RNA
Substantial improvements were recorded in a clinical study of aged patients consisting of presenile, senile, and arteriosclerotic individuals with severe memory loss. Dr. D. Ewen Cameron, of Canada’s McGill University, dramatically demonstrated some striking clinical information by the use of yeast RNA. Memory defects in this group were first measured by the Wechsler Memory Scale, a counting test and a series of conditioned reflex-retention tests. The results after two weeks of RNA therapy were: “Substantial increases recorded in all tests in all subjects.”
Although all patients responded, Dr. Cameron and his research colleagues noted that as a group the arteriosclerotics got the best grades; the preseniles came in second.
It was interesting to note the although there were side effects with the intravenous RNA, oral administration did not demonstrate any reactions whatsoever, even if the dosage was increased over the injectable dosage. It was found that normally the oral dosage took longer for comparable effect, although it was considered safer and less troublesome.
“Before RNA came along, we really had nothing which favorably affected memory defects in these patients,” says Dr. Cameron. “This discovery opens a wide horizon with remarkable possibilities. It is a great thrust forward into the most devastating problem of the aging man—impairment of his memory.”5
Vitamin E and Nucleic Acid Metabolism
The influence of vitamin E deficiency on nucleic acid metabolism was investigated in rats, rabbits, and monkeys. The concentrations of both RNA and DNA were elevated in skeletal muscle and bone marrow in vitamin E deficient states. This can lead to a variety of theories, among them the influence that vitamin E has on the repair process in the body. During a deficiency, the nucleic acids—due to their effect on cellular duplication—increase in order to synthesize the necessary substances needed for cell repair.6
“Messenger RNA” in a Fission Yeast
Yeast cells growing experimentally in culture media were found to have the ability to produce what is known as the “messenger RNA,” which is that part of the ribonucleic acid molecule responsible for the transmission of genetic information from the DNA (desoxyribonucleic acid) of the nucleus to the cytoplasm. It was only after the yeast was transferred to a special media in which the food content was considerably poorer than that of normal media that the step-up in RNA production was noted. This again substantiates the theory that in times of stress the DNA and RNA factors become hyperactive.
RNA Can Be Transferred
Experiments with planarians—or flatworms seldom more than half an inch long— have shed new light on the part that ribonucleic acid plays in the memory process. They possess some anatomical peculiarities, being the lowest animals to have a bilaterally symmetrical body, a central nervous system with a brain, and two symmetrical nerve cords with ladder-like cross-strands and a definite head and tail. They reproduce by binary fission, becoming constricted across the body and splitting into two parts. After fission, in a few weeks the tail regenerates a new head, and the head a new tail.
Planarians have two clearly visible, beady eyes, which do not form images but only react to light. These creatures sense food, move upon it or wrap themselves around it, breaking it up by sucking motions. Small pieces of food visibly diffuse through the translucent tissues. A starved worm survives by digesting itself to a size five or six times smaller than normal, and regrows when adequate food supplies become available.
Dr. McConnell of the University of Texas developed a simple conditioning box in which planarians were subjected to a light for two seconds, then jolted with an electric shock. At first the light was ignored, although the shock resulted in them cringing or making a sharp turn. After 130 or more light-shock pairings, they would cringe at the light alone.
Following this experiment, Dr. McConnell and psychologist Margaret Clay at Ann Arbor began a more complicated study. Due to the ability of the planarian to regenerate a new head and tail when bisected, they cut large planarians in two, discarding the tails and conditioning heads only; they then allowed the educated heads to regenerate new tails, bisected these reconstituted worms again, and finally let the new tails grow heads.
Would these worms, made of tissue entirely regenerated after conditioning, “remember” anything at all? In spite of the repeated hemi-sections, they did; it took them only half as many trials as control worms to acquire the conditioned reflex. Then a further study known as the “cannibal study” in which it was definitely shown that “memory” could be transmitted by feeding pieces of a learned worm to a naive one, proved previous theories.
Further work to determine if actually RNA was involved proved conclusively that it was the RNA factor that provided the memory. If RNA was involved in the learning processes of flatworms, the enzyme ribonuclease— which destroys RNA—would interfere with the retention of conditioning during regeneration. A weak solution of ribonuclease was introduced into the pond water where halves of conditioned worms were reforming and found that educated worm heads retained as much conditioning as heads regenerated in plain pond water. But the educated tails grew up into worms that had “forgotten” everything. There was the evidence sought: RNA, the hereditary messenger, was now directly implicated in the learning process.7
- Nature, July 21, 1962.
- Medical World News, February 14, 1964.
- Nutrition Reviews, Vol. 16, No. 10, 1958.
- Medical World News, Jan. 3, 1964.
- Medical World News, Feb. 1, 1963.
- Biological Abstracts, Vol. 43, No. 5, September l, 1963.
- Medical World News, Feb. l, 1963.
Editorial as it appeared in Clinical Physiology, Vol. 4, No. 4.
Cholesterol is not a fat but a higher alcohol. It does resemble fat in its physical and chemical properties and plays an important part in the body’s transport of fats, but it is actually a steroid. It occurs in the body in a free form and also a cholesterol ester, the form it takes when it combines with fatty acids.
Cholesterol is present in every animal cell, so our main source of ingested cholesterol is animal protein— particularly eggs and cheese. On the other hand, all cells are capable of making cholesterol from the readily available 2-carbon acetate, which comes from carbohydrate, fat, and protein. One of the most important sites for the manufacture is the liver, which is the source of much of the cholesterol that is absorbed from the intestine. The liver manufactures free cholesterol and secretes it into the duodenum in the bile, where it is reabsorbed from the intestine. We also know that animals maintained on a cholesterol-free diet thrive normally and even continue to form atheroma; so can humans with low or normal cholesterol levels.
The Effects of Diet
The source of ingested cholesterol appears to have great influence on the serum-level of it. The same amount of cholesterol in meat will not affect the serum degree as will the same amount from eggs. Penguin eggs affect less than hen’s eggs. More than anything else, the fat content of the diet affects the blood cholesterol level. A meal with high fat content may increase the cholesterol level by 40 to 50 mg percent. This is believed to be due to an increased deposition of fat in the liver that increases the rate of fat metabolism and provides an increased source of acetyl co-enzyme A—the source of endogenous cholesterol. This fat content may be much more important than the cholesterol content of the diet in determining the serum cholesterol level.
—Arthur Grollman in Consultant, p. 10, May 1962.