Embryos, Genes, and Cancer

The sperm and the egg unite to form a single cell. This cell proceeds to divide. The cells rearrange themselves until a fully formed animal is made. What causes this to happen is one of the great unsolved problems in biology.


The pathologists at the turn of the century were fascinated by the similarity of certain stages in the development of embryos to the appearance of certain cancers. There is even a tumor that consists of such a diversity of tissue types that one might consider it to be truly embryonic. It is called a teratoma. The cells that comprise this tumor are capable of becoming almost any tissue imaginable: nerve, muscle, connective tissue, blood, skin, and even teeth and hair. That a single cell is capable of doing this was shown by transplanting single cells, or groups of cells arising from a single cell of a teratoma, into animals; and finding that they still gave rise to the wide spectrum of tissues. This proved that one cell was capable of becoming all of these different tissues, rather than postulating that a whole bunch of different tumors arose at the same time. Of course, fertilized eggs also give rise to different tissues. Teratomas can be artificially produced by transplanting the right piece of embryonic tissue into a mouse of the right strain. That right piece is the part of the embryo that eventually yields an ovary or testis.

An embryo is not a tumor because the cells do what they are supposed to do and the organs and tissues eventually stop growing. We know little more about what makes them stop, than we do about what makes them start again when they become tumors. The explanation of how cancers start does not begin with cancer, or even with the virus which triggers it; it starts with the egg. In order to understand the egg, we must go back and study the virus again; but not the virus as a destructive disease-causing agent, but as a basic life form.

It is necessary to understand, much more thoroughly than we do now, how the egg unfolds to yield a complete individual; what the Germans called "developmental mechanics." While we are in the business of unraveling this, it is also important to understand the development of the fully formed individual; how his cells function, and how the entire organism functions.

As far as we know today, it is the genes that tell the cells what to do. A small amount of experimental evidence indicates that every cell in an individual has the same number and kinds of genes. This was done in frogs by taking the nucleus out of an egg and replacing it with the nucleus of an intestinal cell. At least some of the eggs that were handled in this way were developed into normal frogs. That kind of evidence is very convincing, and if it happens in frogs, it probably is basic and happens in everything else. The mechanism probably originated long before frogs or people were invented. If this is true, then every cell in our bodies has all of the information necessary to create another human being identical to us; but it doesn't do it. Not only that, but every cell has the capacity to become every other kind of cell. If one cell becomes a tumor, every other cell is capable of doing the same thing. None of these things happen; cells usually preserve their identity for the lifetime of an individual. No one knows why. If we are going to attempt to solve the cancer problem, here is one good place to start, among many others.

Every cell has a large number of genes. Of these, only a fraction are needed at any one time. The genes for making black pigment, for example, are not needed by cells in the liver. The genes that tell the cell to make mucus are not needed by skin cells, and so forth. There are a number of genes that probably function only in the embryo. Molecular geneticists talk about genes being turned on and being turned off. The precise way in which this mechanism functions is not known. Genes that were functioning in the cell could be turned off, or genes that were not functioning could be turned on. When this happens, the cell will behave differently from the way it did before the change.

Each one of us started as a single cell and, theoretically, all of our cells have the same numbers and kinds of genes. In practice, this is not true. All genes are subject to mutation (a change in the gene), and mutations occur continually. The mutation can consist of a small change in the gene itself, a rearrangement of the genes on the chromosomes, or the addition or loss of segments of chromosomes or of whole chromosomes. There is, therefore, a large amount of genetic variation in the cells of our bodies. Many mutations or chromosome changes are incompatible with the life of the cell, and the cell carrying the mutation simply dies. Others are of no consequence and the mutation is passed on from cell to cell, but does nothing to effect the cell's function for better or for worse. Still others may effect a cell only slightly. It may cause it to multiply a little faster or a little slower. If it causes it to multiply faster, then the cell will have a "selective advantage" over its neighbors and it won't be long before most of the cells in the area are of the same constitution as the mutated cell. If, on the other hand, the cell does not do quite as well, it will be at a selective disadvantage and will probably be replaced by more successful cells. The same laws of natural selection that apply to populations of bacteria, fruit fies, animals, and plants also apply to populations of cells within the body of the single individual.

Genetic information can be added to a cell by the addition of a virus made up either of DNA or RNA. A DNA virus can incorporate into the cell and function as an additional gene, and an RNA virus is capable of producing changes in the information carried by the DNA.

Substances that inhibit cell division are found throughout nature. We know that they exist, not because too many of them have been isolated, but because of their well documented effects. Certain plants will prevent the growth of others, and it is now well established that the presence of certain bacteria will inhibit the growth of other bacteria. In bacteria, this mechanism is extremely useful to man and to other animals that harbor intestinal bacteria. Some of the normal bacteria which do not cause disease can inhibit the growth of disease-causing bacteria. It ordinarily takes a very large dose of typhoid or paratyphoid organisms to produce an infection. In an animal without normal organisms, this can be accomplished with only a few bacteria. This phenomenon of the inhibition of one organism by another goes by the name of antibiosis, and the substance that is isolated is called an antibiotic. If the antibiotics produced are not poisonous to man, then they become very useful drugs. You might remember, however, that bacteria knew about antibiotics long before we did. This phenomenon may have evolved along with other organisms, with the result that all cells now produce some kind of substance that inhibits cell division around them. When the concentration of the cells becomes high enough, all cell division activity stops. These substances that inhibit cell division go by the name of chalones (pronounced kalones).

It is not really contradictory to say that a good deal of work has been done in an attempt to clarify the role of growth inhibitors and stimulators in a wide variety of cells, but the surface has barely been scratched.

If we are to understand cancer, we have to understand the basic laws of life; and nature keeps these well concealed. What we know about cancer today is less a function of what the people who have studied cancer have found out than it is a function of what has been discovered about biology in general. Every advance in science, particularly in biology and biological chemistry, has an application to the study of cancer. The domain of cancer research is, in fact, the domain of experimental biology.

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