Has evolution found ways to prevent cancer and halt progression to old age?

By Prof.Kirthi Tennakone

The high incidence of cancer alarms us. Around six percent of the human population worldwide suffers from cancer. It is the most challenging health issue to resolve and the leading cause of death, only second to cardiovascular disease. More than 10 million people die of cancer every year. In some regions, cancer deaths exceed heart disease mortality because of the availability of more successful preventive and curative measures for the latter.

With all these fears, the relief and the promise are cancers occur less frequently than expected. Many live beyond 100 years without contracting cancer but die because of other natural causes. Animals also get cancer, but there are species exceptionally resistant to it. And evolution has found solutions to suppress malignancy. Following them would be a hopeful avenue to prevent and cure this dreadful malady.

DNA damage, the primary cause of cancer is also a factor that induces our progression to old age. Evolution seems to have found clues to address both problems in one stroke.

Cause of cancer

Nearly 40 trillion cells of different kinds constitute our bodies. All of them carry the same genetic material (DNA) unique to the individual but some express only a portion of the encoded genetic information. Cells divide constantly to produce new cells for growth and replace those that naturally die. Each day, several trillion cells divide, replicating the DNA, and copying the mode of genetic expression. The replication, prone to random error, may not be exact, sometimes leading to mutations. Cancer is caused by mutant cells with altered genetic expression. Even one such mutant cell could cause the disease because it can divide and multiply. According to the above scenario, multicellular organisms are inherently subjected to the threat of cancer. Environmental influences such as pollutants and radiation could indeed induce malignancy in normal cells. Even if these external triggers are eliminated, cancer occurs because of molecular accidents in the process of cell division. Most of the time, someone getting cancer is not the fault of an external cause or a habit. Of course, this wouldn’t mean that the prevalence of cancer is not increased by external influences and habits. Exposure to mutagenic chemicals, radiation and many habits notably; chewing betels, alcohol and smoking has been proven to increase the risk of cancer.

Multicellular life

Life on Earth originated about 4 billion years ago. The primitive forms of life were self-replicating molecules created in prebiotic oceans via a yet unknown process. Fossil evidence suggests single-cell (unicellular) microbes appeared 3.7 billion years ago. They acquired more and more capabilities via several steps of evolution and finally gained a propensity to agglomerate into colonies – macroscopic structures or blobs made up of the same kind of cells.

The pivotal epoch in biological evolution was the period beginning about 600 million years ago when multicellular organisms with colonies of specialised cells emerged. Cells in all the colonies contain the same DNA but specialised by closing the expression of some coded information and manifesting selected genes. This mechanism provided animals and plants with organs cooperatively interacting with each other for the benefit of the organism. The division of biochemical and physical functions between different organs was an unprecedented adaptive advantage – multicellular life diversified, dominating the earth. The strategy is analogous to the division of labor as society advances. Primitive humans, although they liked to segregate, each undertook all essential tasks such as gathering food, building shelter and making tools. Later, they abandoned some tasks and specialized. There were farmers, carpenters, smiths and physicians; cooperatively working together for mutual benefit.

The fact that multicellular organisms evolved from a unicellular microbe remains latent in their developmental process. All animals and plants begin their lives as single cells that divide, differentiate and expand spatially according to a plan written in the genetic code. Billions of years of evolution have perfected the scheme. Yet, multicellular life encountered three inevitable biological hurdles; infection, carcinogenesis and aging, leading to death.

Microbes (mostly unicellular) invade multicellular organisms, causing disease. Mutations introduced during DNA replication or due to external influences such as chemicals in the environment or radiation cause cancer. Irreversible chemical changes in the body lead to aging and eventual death.

Evolution attempts to find solutions to every problem confronting life. The immune system fights invading microbes to prevent infection, a similar mechanism eliminates mutated cells causing cancer and repair processes prolong life.

Peto’s paradox

Every cell in the body of an animal has a non-zero probability of giving birth to a carcinogenic daughter cell as a random uncontrollable event during cell division and proliferate developing tumors. Therefore, larger- bodied animals carrying a greater number of cells should be more susceptible to cancer and very large animals would go extinct because of carcinogenesis.

In 1776, the English epidemiologist and statistician Richard Peto pointed out among animals there is no correlation between body size and incidence of cancer. The absence of the expected relationship between body size and the incidence of cancer is referred to as Peto’s paradox.

Elephants and humans have similar life spans, but the former are built out of nearly 100 times more cells than the latter. If the risk of cancer relates to cell content, the prevalence of the condition in elephants would be so high that almost every one of them will prematurely die of cancer. However, elephants are known to be highly resistant to cancer, with an incidence estimated to be five times lower compared to humans. Whales are thousands of times bulkier than humans and known to live 200 years or more. These gigantic animals live so long because they have acquired an exceptional resistance to cancer. A few dinosaur fossils indicative of bone malignancy have been discovered. Undoubtedly, cancer in these reptiles was very rare. Otherwise, they could not live long enough to reach extraordinary sizes and dominate the earth for 160 million years.

The fact that big made individuals in the same species are more likely to have cancer than small made indicates the Peto’s paradox is evolutionary in origin.

How do these giant animals resist cancer? Elephants have 20 copies of the gene named T53, whereas humans and most mammals have one. The gene T53 gives instructions to synthesize a protein P53, which acts as a tumor suppressor facilitating the repair of damaged DNA. Whales are believed to adopt a similar technique to eliminate malignant cells.

Gigantism favors animals to repel predators and easily feed by roaming around. However, a large enough number of these animals cannot grow to massive sizes and reach reproductive age, without suppressing carcinogenesis. Small animals reach maturity early and have shorter life spans and cancer would not be a threat to the survival of the species.

Naked mole rat: an animal that keeps cancer at bay

The naked mole rat is one of the most fascinating animals we have on this planet. A subterranean mammal about the size of a domestic mouse and distantly related to it. Lives in arid regions of East Africa, borrowing kilometers – long tunnels 1-2 meters below the ground. A strict vegetarian feeds on roots and tubers and never drinks water. Their bodies are pinkish with sparingly distributed hair, accounting for the name they earned. Protruding incisor teeth help it to dig tunnels even in hardened dry soil. The animal is virtually blind and senses the environment mainly by the tactile facility of its hair. Mole rats are social animals governed by a queen who associates one or two princely mates, reproduces and supervises a colony of about three hundred members, giving vocal commands. All other females and males are sexually inactive workers who dig tunnels, take care of young and serve the royalty. If the queen dies, females fight to the death and one who succeeds in securing the ‘throne’ becomes sexually active.

A mole rat lives more than 40 years, showing no apparent signs of physiological aging. The queen lives longer and continues to reproduce. Related animals of similar size live only 2-3 years. Mole rats are resistant to infections and tolerate very low levels of oxygen without asphyxiation. And most importantly keep cancer at bay – no evidence of cancer in thousands of animals examined, except one or two zoo animals. They die of tunnel accidents or snake attacks when they reach heavily guarded tunnel vents.

Current research has revealed mole rats possess tumor suppressing genes. They give instructions to repair damaged DNA and produce agents that inhibit tumor growth. Perhaps, the same genes effectively suppress ageing. One of the main causes of human and animal aging is genomic instability, the failure to repair DNA deteriorating in replication or due to chemical influences. These are also the primary biomolecular events responsible for cellular carcinogenesis.

Recently, longevity genes of mole rats have been successfully transferred to mice. Amazingly, an increase in life span and a betterment of health were observed. In the future, similar procedures may rejuvenate youth in humans! After all, the effort of the alchemists of antiquity to find an elixir of immortality may not be entirely absurd.

Unprecedented healthy longevity of mole rats is a lesson to humans.

We humans live in an elusive atmosphere of a brightly lit carnival, do everything possible for pleasure, curiosity and economic advantage, but have failed to resolve imminently crucial issues, good health free of cancer, neurodegenerative diseases and rapid aging. The naked mole rat living in dark ill – ventilated narrow tunnels beneath the ground has solved these problems. Humans need to look at the workings of animals more closely and preserve their habitats.

The author can be reached via email: ktenna@yahoo.co.uk