Cancer - Within The Cell
( Originally Published Early 1960's )
The new biological frontier.
It is no exaggeration to say that the last decade has witnessed discoveries concerning the structure, synthesis and function of living matter that are as profound and as far-reaching as the discoveries of Louis Pasteur and other microbiologists of the 19th century. A new discipline, molecular biology, has arisen, and some of the work already has been rewarded by three Nobel prizes: to George W. Beadle, E. L. Tatum and Joshua Lederberg of the United States in 1958; to Severo Ochoa of Spain and the United States, and to Arthur Kornberg of the United States in 1959; and to James D. Watson of the United States and F. H. C. Crick of Great Britain in 1962. These advances have direct application not only to cancer, but to virus diseases, metabolic disorders, congenital malformations and even to the manipulation of genetic characteristics.
The cell is composed of a darkly-staining, compact nucleus, a liquid cytoplasm around the nucleus containing particles some of which are called ribosomes, and the cell membrane enclosing the structures. The nucleus contains chromosomes, discrete strands that carry the genetic orders that determine whether the cells develop into men, mice, or whales, whether the individual has blue eyes or black, and whether he will or will not be susceptible to one or another disease.
In man, there are 46 paired chromosomes, as established only in 1956. Until then, due to an old error of observation, it was taught that man possessed 48 chromosomes. With modern techniques of tissue culture, squash preparation of the cells, and the stopping of cell division at a point when the chromosomes separate by the use of a drug called colchicine, a whole series of important observations became possible. One pair of the chromosomes determine the sex of the individual: an XX pair resulting in a female, and an XY pair resulting in a male. The sex chromosomes look different, and the sex of a person can be determined by looking at his individual cells. Sometimes an extra sex chromosome is found, and such persons may be sterile and show other sex abnormalities. A very specific chromosome abnormality is always seen in a mental deficiency called Mongolism, recently renamed Down's syndrome. In one form of cancer, chronic myelogenous leukemia, there is often a specific chromosomal abnormality, the so-called Philadelphia chromosome.
The chromosomes consist of tightly coiled double strands of a molecule that has an external backbone of sugars, and internally interlinked, in a zipper-like fashion, a series of nucleic acid components. These molecules, with molecular weights of several million, are called desoxyribonucleic acid, or DNA for short. They govern not only the genetic continuity of the species, but all the essential processes of the life of the cell.
The arrangement of the four nucleic acid components along the DNA molecules determines these operations in a manner analogous to the instructional tapes of the computers. For the reproduction of the cell by division, the DNA strand unzippers itself into 2 halves, and from the raw nucleic acid building blocks and other components in the cell, constructs an exact copy of the half-strand, and then segregates the identical chromosomes for the mitotic phase of division.
The chromosomal DNA is also the manager for the daily life functions of the cells, which it guides through two other key chemicals. These are: RNA, much smaller, single strand molecules of nucleic acid arranged along a more soluble form of the sugar, ribose; and proteins. The RNA molecules are formed in the nucleus according to the blueprint of the DNA, and these messengers proceed into the cytoplasm to attach themselves to the ribosomes. There other RNA molecules convey the amino acids for assemblage into the operational proteins such as enzymes.
A reasonable analogy may be fashioned with the activities of a newspaper. The nuclear DNA is the editor. The mes senger RNA molecules are copy boys that carry the editorials to the typesetters, the cytoplasmic RNA, that take the letters of nucleic acid and set them into the ribose slots in accordance with editorial directions. There are the workers that melt out-worn letters, and other workers that remake new letters for further use; these are the enzymes. In this analogy, the Owner of the newspaper remains the hidden mystery.
In order to exist, the cells of the body must obtain oxygen for their respirative functions, a whole series of nutrients as sources of energy, and amino acids, vitamins and other essential chemicals that they cannot manufacture themselves for the building blocks to replace and substitute worn out or lost portions of their structure. The body and all its component parts are in a constant, active state of dynamic equilibrium. One of the great contributions of the use of stable and radioactive isotopes as tracers of biological reactions was the demonstration that there are no "fixed" tissues, that all tissues and cells of the body constantly replace themselves in part, substituting new molecules for old.
In the dynamic state of biological life, the myriad of chemical reactions must occur within a limited range of temperature, yet they must occur rapidly and smoothly. Even such a relatively simple event as the transfer of oxygen through a membrane between the air sac of the lung and the blood would take too long at the body temperature of 38° C. All such reactions or transfers, splitting into component parts, and the synthesis of new complexes, are mediated through the action of specialized proteins called enzymes. Several hundred of these, from aldose to zymohexase, have been identified, and many have been isolated and crystallized. The enzymes are manufactured from amino acids by the RNA on instructions from the genic DNA of the cell, and go forth to regulate the life chemical processes in the cells or at sites distant from the cells. Enzymes do not participate in the chemical reactions but accelerate their process.
Vitamins are of importance because they may form a part of certain enzymes, but the body cannot synthesize these parts of these enzymes and must obtain them from its environment. Closely allied in activity to enzymes are chemical cell products called hormones, which also regulate at a distance many of the metabolic and endocrine functions of the body. The pituitary protein hormones act as the thermostat in the coordination of another large species of steroid hormones.