Cancer as an Evolutionary Response – January 2, 2011

Of all the diseases and disorders to which flesh is heir, the most intractable seems to be cancer—or, more properly, “the cancers,” as there seem to be as many types of cancer as the organs and tissues affected.1 This is frustrating, because we can find and isolate the virus that causes the common cold and the bacillus that causes tuberculosis. We can trace out the immune system breakdowns that lead to asthma or multiple sclerosis. But cancer remains a complicated mystery, of which we can only discern the edges and effects. This leads me to ask, what if cancer is not a disease at all, in the usual sense of the word, but instead an evolutionary response?

Cancer is not your typical “genetic disease.” When we think of such diseases, it’s usually a single-point mutation arising in a specific gene which causes its protein to be ineffective. For example, a coding deletion in the protein that regulates a cell membrane’s ability to pass molecules like sugars and peptides results in cystic fibrosis. And any one of several mutations that damage one of the proteins in the cascade that facilitates blood clotting can result in hemophilia. These are mutations that exist, or not, in the parent and can be passed on, or not, to the offspring, usually as recessives—which means that both chromosomes must carry the defective gene for the disease to arise. Right now, the most we can say about cancer is that some genes and their mutations give a person an increased risk for it.

The occurrence of cancer is also subject to mutating forces that arise in the environment, such as exposure to radiation or various toxins and viruses. But it’s not always possible to link one of the cancers to any specific mutation or even to a single mutating event. Intense radiation exposure, for example, does not immediately raise a crop of tumors, although they may appear years and even decades after a recorded exposure. And some cancer-related diseases, like Hodgkin’s lymphoma, appear to throw off tumors as a symptom or side effect while the disease itself arises from some cause that precedes the tumors.

Cancer is certainly a genetic disease in the sense that something goes terribly wrong inside the nucleus of a cancer cell. Researchers have described the nuclear consequences of an active cancer as a genetic disaster, with many extra copies of various chromosomes present in the nucleus. But such an explosion—a catastrophic “going wrong”—cannot account for the subtle mechanisms that make the tumor itself viable. Consider three specific mechanisms that every tumor employs.

First, tumors need to overcome the natural limits to growth and lifespan in most cell lines. Telomeres are the genetic structures at either end of a chromosome that support duplication in advance of cell division. These structures normally get shorter with each copy made from the cell, providing a count-down mechanism that limits the number of cell divisions and so limits the age that any single cell can reach. However, the body also produces telomerase, an enzyme that can repair and lengthen the telomeres. This process allows certain cells—or cells at certain times in their life, such as in the developing embryo—to grow beyond the natural limit. Telomerase production is normally suppressed in cells that are supposed to live and divide for a while and then eventually die out. But cancer cells appear to release telomerase through their own processes to aid their wild and uncontrolled growth.

Second, tumors need their own blood supply if they are to grow beyond about one millimeter in diameter, a mere pinhead. Cells at wound sites normally release enzymes that promote the sprouting of new blood vessels from existing ones, a process called angiogenesis, to support the growth of new tissue. Cancer tumors are also able to release these enzymes to promote blood supplies for their own growth.

Third, tumors release into surrounding tissues their own kind of cancer stem cells. Once these cells travel to other parts of the body they grow new tumors of the same type. This is how cancer spreads, or metastasizes, and colonizes new tissues and organs. And this is why simply removing a tumor surgically does not guarantee an end to the cancer.

Clearly, while cancer is a nuclear disaster and a kind of genetic insanity, there is a method to its madness. The cancer tumor acts more like a new kind of organ—a malignant and treacherous one, to be sure, intending the body only harm—than a simple failure of existing organic mechanisms such as in cystic fibrosis or hemophilia. In fact, if you wanted to design a “self-destruct” mechanism for the body, you could do worse than plant a “cancer bomb.” It’s not as fast acting as a hypnotic compulsion to jump off a cliff, but it operates automatically and is not subject to whim, reason, or volition.

As a convinced evolutionist, when I see a complex mechanism at work—one that goes beyond a mere accidental breakdown like a single-point mutation—I tend to think it may be an evolutionary response to some environmental pressure.

There’s an obvious problem with this thought, of course. Most evolutionary changes take effect in the organism before the onset of breeding. Immediate benefits help the organism survive in order to pass its genes along to the next generation. Or detriments take the organism out of the breeding mix before the genes are passed. So how can an evolutionary response operate when it doesn’t, in most cases, appear until long after the organism has bred the next generation? How can cancer be an evolutionary artifact when it strikes mostly mature or elderly people?2 How does that benefit the next generation?

Consider that, in the case of humans at least, we have the potential to live far longer than our breeding age. A human becomes fertile at 12 to 14 years. In a natural state, such as the hunter-gatherer cultures that dominated most of our history as primates, a human can have its first child at about 13 years old. If that child becomes fertile and breeds in the normal course, then the parent becomes a grandparent at about age 26, a great-grandparent at 39, a great-great-grandparent at 52, and so on. Clearly, it is beneficial to any generation to have a set of parents to care for and nurture the young. It is also beneficial to have grandparents, who can undertake that care while the parents are out foraging and can also pass along the skills and wisdom learned over a lifetime. But great-great-etc.-grandparents are superfluous.

Barring accidents and misadventure, a normal human body can live to age 80 or 90.3 Of course, most people did not live so long in the rough-and-tumble world of the hunter-gatherer. But if a largish fraction of the population were to attain 50 or 60 years, in a time when the span of a generation unmodified by social conventions was about 15 years, then you have a plague of great-great-grandparents competing for victuals around the campfire. Considering that old people can be crafty, authoritarian, and insistent, that’s going to be bad for feeding the younger generations and the rug rats. And those young ones are precisely the generation that the future needs. Some evolutionary mechanism that abets the accidental cliff fall and lurking leopard in taking out the surplus old ones would be good for the survival of the next breeding generation.

Consider also that environmental stress seems to be linked to cancer and, although study results are conflicting, there may be a further link between psychological stress and cancer.4 Crowding, reduced food supplies, intense competition for the daily necessities—all can weaken the immune system and cause bodily harm. One of the harms may be an increased incidence of cancer. So, when the supply of berries and small game puts pressure on the hunter-gatherer clan, the old ones will weaken and sicken and die, to the advantage of the young.

All of this is speculation, of course. Cancer might just be one tough nut of a disease to figure out. But if it’s something more, if it’s a mechanism developed by evolution for a purpose, then unlocking cancer may require a change in our medical perspective. Cancer as an evolutionary byproduct that is bad for the individual but, in the worst of times, good for the species may require different approaches to diagnosis and treatment.

Modern medicine is all about survival of the individual. But, as biological examples have shown again and again, evolution cares only for the health and fitness of the overall population. Our understanding of cancer may be caught between the two paradigms.

1. I once thought the only tissue immune to cancer was the muscles. After all, you hear of bone cancer, brain cancer, skin cancer, but you never hear of heart cancer or quadriceps cancer. But ten seconds with the Google search engine turned up “soft tissue sarcoma,” which develops from fat, muscle, nerves, and fibrous tissue in any part of the body. Cancer seems to be everywhere.

2. There are childhood cancers, to be sure, mostly brain cancers and leukemias. But common adult cancers such as those of the lung, breast, colon, and stomach are rare in children. Clearly, if cancer is an evolutionary auto-destruct mechanism, it’s an unruly and imperfect one. But then, it’s always dangerous to place a bomb in a structure—the chance of it accidentally going off is going to be high.

3. Consider, in The Iliad, the character Nestor, King of Pylos, who is a white-haired old man. Based on his ruling the “third generation” of his kingdom (figured by scholars at about 30 years for each generation) and on the various wars and adventures he is said to have experienced, his age is put at about 85. That’s a remarkable age, given the rough times and Nestor’s active life, but it’s clearly not unheard of. Nestor’s age is not presented as any kind of marvel or the result of divine intervention.

4. Certainly people who have experienced a grave emotional setback, life reversal, or deep loss seem also to develop cancer as one of their woes. For example, during the turmoil that ended his reign, the Shah of Iran developed lymphatic cancer.