Cancer Cells And Organisms
( Originally Published Early 1960's )
The basic biological unit of plant and animal life is the cell. All higher animals that multiply by sexual reproduction begin with the union of the male and female sex cells, which are specialized cell units containing only half of the genetic material characteristic of the species. The resultant divisions of this union eventually form the whole organism.
The original few cell divisions are symmetrical, but if this continued, we would be monotonous spheres. Soon the cells orient themselves along a longitudinal plane and the mass begins to assume increasingly different shapes at various points. This is the phase of differentiation, in which from the originally identical cell units there arise the different tissues and organs of the body. Eventually, from the original fertilized egg there develops a complex, closely integrated community of some 100 billion cells that comprise the adult human body. Each one of these cells has the genetic identity of that individual, yet the cells can be as different as those that make up the brain, the liver and the skin. Some tissue cells continue to divide at relatively constant rates throughout the life of the individual, replacing the worn out cells and thus maintaining a dynamic equilibrium. This is the case for the skin, which is continually replaced from the deeper layer. Other tissues, such as the liver, have the power to replace cells following injury or removal of part of the organ. Still other cells, among them those of the central nervous system, are so specialized that they lose their property of being able to replace themselves by division.
As important as the process of differentiation, which converts a round ball of a few dozen cells into mice, whales or human beings, is the process of regeneration or healing. When a tissue is injured so that some of the cells are destroyed, ordinarily the remaining cells divide to bridge and repair the damage. If this damage is too great, or if it involves cells that are unable to divide, the special connective tissue cells complete the repair by forming scar tissue. In both the process of differentiation and of healing, the remarkable feature is that the cells "know" when to stop dividing.
A technique which has been most useful in the study of cells is known as tissue culture, first introduced by Ross Harrison of Yale in 1907. A small fragment of tissue, usually from an embryo, is placed in blood plasma, and maintained under sterile conditions in a small flask in moist, warm conditions. The cells from the tissue will continue to grow and to divide, and can be observed under the microscope and photographed. Under optimum conditions certain tissues may continue to multiply indefinitely. Alexis Carrel of France, a good showman as well as a Nobel prize winning scientist, celebrated for many years the birthdays of such a tissue, first derived from the heart of an embryo chick. He would point out that were the cells able to divide without limitation, their mass would have exceeded that of the earth.
It is this built-in limitation of growth, the acquisition and maintenance of function, the dynamic equilibrium between various parts and organs, in other words, the planned discipline of an integrated complex colony of cells of the individual that distinguishes normal growth and cancer.
Cancers of all kinds are tissues, too. They are composed of cells, as can be observed under the microscope. Many of the cells are somewhat larger and abnormal in shape, but even more resemble the normal organ tissue from which they arose and by which they can be identified. Many cancers form glands and secrete the same materials as the glands they mimic. But the restraint of growth is missing, and instead of stopping their reproduction at the appropriate boundary, the cells continue to divide, invade and behave in a manner that is not compatible with the integrated behavior demanded of normal tissue. Cancer growth is not necessarily more rapid than normal growth. In fact, many normal growth processes exceed those of mass cancers. Among these are embryonic growth, which develops from one cell to a 7-pound baby in 9 months. But the baby is then ready to emerge into the world, to continue its well regulated growth; for cancer there is no such end point.
Cancer cells, too, can be grown in tissue culture. In this environment also the division rate of cancers is often no more rapid than that of connective tissue cells. But their lack of integrated behavior is again evident. Normal connective tissue cells grow in smooth, 1-cell thick layers on surfaces provided for them, producing net like structures; when a cell encounters another cell, further division is inhibited or proceeds in another direction. But cancer cells tend to grow in clumps, and the proximity of their neighbors does not inhibit them. Instead, they climb on each other, and as a consequence choke off some of their kind from the food and oxygen supply.
That cancer is a process affecting the cell is further shown by experiments involving the transplantation of cancers from one animal to another. This was first performed successfully in dogs by a Russian veterinarian, M. Novinsky, in 1877. When inbred animals became available, the transplantation of cancers from one animal to another of the same genetic constitution could be carried out with uniform success. Small bits of sterile cancer tissue are taken from a mouse or a rat and injected under the skin of another mouse or rat of the same strain. After a short time, the cancer starts growing in its new location, by the multiplication of the cells that comprise it, and so on through a whole series of animals. Some transplantable tumors have been maintained in this manner since the early years of this century, and are known by the names of their original discoverers. This continuity of the tumor with maintenance of its appearance and behavior through many generations indicates that the cellular change involves a permanent change in either the genetic mechanism of the cell, or some transmissible, reproducible material within the cell. When the tumor tissue is ground so finely as to destroy all the cancer cells, or the material passed through a filter that holds back all cells, no tumors will arise at the site of transplantation.
In 1936 Jacob Furth of New York took another step in the demonstration of cancer as a disease of the cell by transplanting tumors from one mouse to another with single cancer cells. And in 1943, the late Wilton Earle and his associates at the National Cancer Institute published their meticulous studies on the conversion of normal cells to cancers in tissue culture. Whatever the mechanism of this conversion, it was again shown that it occurs at the level of the cell, without the need of the whole organism and its many reactions, and that this conversion is a permanent one transmissible to the progeny of the cell.