Problems with the Somatic Mutation Theory

By Linda L. Isaacs, M.D.

The most commonly accepted theory of how cancer develops, frequently presented to students as a fact, is the Somatic Mutation Theory. In this model, cancer develops because of changes in the DNA, the genetic material of a mature cell, due to aging, toxic exposures, radiation, etc. Decades ago, one mutation was thought to be enough. Now, as more and more presumed carcinogenic mutations have been found, many scientists believe it takes many genetic changes for a cell to turn into a cancer.

Any theory requires re-evaluation as new information becomes available. And there are problems with this theory, as described in a 2022 article in the Journal of Cancer.

Here are the issues the Journal of Cancer article lays out.

Paradoxes

Changes in genetic structure are more likely to occur during cell division. If cancer comes about because of genetic changes, cancer should be most common among cells that divide frequently. But not all rapidly diving cells are prone to cancer. Hair follicles produce new hairs constantly. Cells that line the small intestine are replaced every 2-3 days. Yet cancer is rare in both locations.

There are toxic compounds that affect DNA and do not cause cancer. There are toxic compounds that cause cancer and do not affect DNA.

Some tissues in the body accumulate mutations thought to be carcinogenic, and yet no cancer is seen. For example, in a study of tissue removed in cosmetic eyelid surgery, the skin appeared normal. No cancer or pre-cancer was seen. Nonetheless, many of the cells had a number of these mutations present.

Cancer caused by changes in the tissue, not mutations

In animal experiments, implanting a foreign body can induce cancer. This can happen in humans as well; asbestos is an example. A foreign body should not cause mutations.

Some non-cancerous cells migrate, as cancer does, without any mutations

White blood cells migrate throughout the body to perform their role of immune surveillance. Embryonic cells reproduce, migrate, invade, and create blood supplies as part of normal development. The Journal of Cancer article reviews in detail the similarity of cancer to cells of early development.

Experimental models of transplanted stem cells and cancer cells

On this point, the Journal of Cancer review is quite technical. To summarize, various experiments have shown that normal stem cells, if transplanted into an animal, can become cancerous without damaging exposures. And, cancer cells transplanted into embryonic tissues can become normal cells. If the Somatic Mutation Theory is correct, a cancer cell should not be able to become normal, because its genetic material has been irreversibly damaged.

Cancer regression

The Journal of Cancer article provides a lengthy discussion of cancer regression, which happens in cell cultures, in experimental animal models, and in clinical medicine. But again, if the Somatic Mutation Theory is correct, regression should not happen.

Supporters of the Somatic Mutation Theory have explanations for many of the above points. For example, clinical cases of spontaneous regression are explained by activation of the immune system, which then destroys the cancer. (This would not explain spontaneous regression in cell cultures.)

But when explanations to support a theory become more and more complicated, it may be time to look at other theories.

Next Section: Alternatives to the Somatic Mutation Theory

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