Peto’s Paradox

What is Cancer?

To understand cancer, we must first understand the cell. The cell is a complex structure run only by biochemical pathways or interactions of proteins, that constitutes the magic we know as life. This system is not complete, however, and it is susceptible to mistakes. In complex organisms (multicellular organisms) that require billions of cells to work together in sync, there cannot be a rogue cell that cannot function properly with the other cells. Therefore, cells in multicellular organisms have a kill switch that makes the cell undergoes apoptosis in which the cell commits suicide when the cell senses that a part of their system has gone wrong. Sometimes, apoptosis doesn’t function properly and the immune system kicks in. As an example, a macrophage of the immune system could eat the cell that failed to commit apoptosis. But, even this kill switch and secondary measure is not infallible. When a broken cell manages to escape these, it becomes cancer.

Peto's Paradox

The size of a cell in all animals are similar. The only factor is the number of cells and not the size. A rat cell would have roughly the same size as a human cell or a blue whale cell. The chance for a cell to become a cancer cell is similarly the same for all animals and that would mean that humans would have a much higher chance of developing cancer than rats, because of the sheer amount of cells. But, in the natural world, this is not the case. Bigger animals show the same rate of cancer as smaller animals, and bigger animals like whales seem to be immune to cancer. This is the Peto’s paradox.

▲Peto’s Paradox [5]

Possible Explanations

2 possible explanations that have been explored, but the answer to this paradox has not been discovered as of yet.

Evolution

▲Tumor Suppressor Genes [3]

The first possible explanation is that through evolution, animals that grew larger bodies encountered this problem and built a counteractive system to prevent cancer. For cancer to form, several specific parts of the genes need to become corrupt. These genes are called proto-oncogenes. When these proto-oncogenes mutate, that is when cancer forms. What I mean by “several specific”, there are multiple mutations necessary to create cancer. One would be a mutation to disable the gene that causes apoptosis. Another would be a mutation to be able to hide from the body trying to detect cancer. There might also be another mutation which would allow the cancer to redirect blood vessels to itself to accelerate growth by feeding off of the bodies resources. But, these proto-oncogenes are not left alone. There are tumor suppressor genes that look after the proto-oncogenes, and when the proto-oncogenes mutate, the tumor suppressor genes either repair them or commit apoptosis when it decides that it is beyond repair. It turns out that larger animals possess more of these compared to smaller animals. So, a human cell would need more mutations to occur to become a cancer compared to a rat cell. This natural adaptation must come with a cost, but scientists have not discovered that yet.

Hypertumors

▲Hypertumor [4]

The second possible explanation is called a hypertumor. This hypertumor which may sound intimidating is just a tumor of a tumor(named after the hyperparasite (the parasite of a parasite)). Like mentioned in the introduction of cancer, normal cells are required to cooperate with other cells. The formation of cancer can be described as a breakdown in cooperation. The birth of a selfish cell that only cares about itself. The cancer now free from the system of apoptosis, now have a higher tendency to mutate, and eventually one of the cancer cells would mutate enough to think of itself as an individual, creating the cancer of a cancer. The limiting growth factor of these cancers is how much nutrients it’s getting. Cancer cells trick the body to redirect blood vessels to speed up its growth. But, since there are now 2 different cancer cells, they compete for this nutrient source. The new cancer would redirect the blood vessels from the original cancer to themselves which would starve the original cancer and kill them off. This process can repeat indefinitely as long as the host continues to live. For large animals, this tumor can be negligible in size. For example, a 10g tumor would take up a much significant portion of a rat’s body, than it would for a human and the same thing could be said for a whale, in which 10g for a whale would be comparable to nothing. It is possible that larger animals have a lot of these hypertumors, but they constitute such a small portion of their body mass that it hardly becomes a problem.

What About It?

Animals tend to evolve bigger, but this may be one of the reasons why. In its history, human heights are usually correlated with the amount of nutrients they had available at the time. Therefore the sudden increase in modern human heights are described as the effect of a stable food supply. But, it is also possible that with cancer now being the leading cause of death for people in many countries, nature has found a way to lower these percentages by increasing body mass in general.

[1] 2019. “Handbook of Health and Welfare Statistics 2019 Contents”. Ministry of Health, Labour and Welfare. https://www.mhlw.go.jp/english/database/db-hh/1-2.html. 2020/04/17.

[2] 2020. “Why Blue Whales Don’t Get Cancer – Peto’s Paradox”. Kurzgesagt. https://www.youtube.com/watch?v=1AElONvi9WQ. 2020/04/17.

[3] 2012. “Tumor Suppressor Genes”. Cancer Biomarkers. http://www.cancer-biomarkers.com/2012/07/tumor-suppressors.html. 2020/04/17.

[4] Shreyas Tanna. “Hyper tumor: Evolution’s way of fighting cancer”. Medgazette 24. http://www.medgazette24.com/hyper-tumor-evolutions-way-of-fighting-cancer/. 2020/04/17.

[5] 2017. Carlo Maley. “Peto’s Paradox”. ResearchGate. https://www.researchgate.net/figure/An-illustration-of-Petos-Paradox-Cancer-is-a-disease-of-uncontrolled-cell-growth-and_fig1_318415292. 2020/04/17.

[6] 2020. Alison Cranage. “Cancer across the animal kingdom”. Sanger Institute. https://sangerinstitute.blog/2020/02/16/cancer-across-the-animal-kingdom/?utm_content=buffer8c2cd&utm_medium=social&utm_source=twitter.com&utm_campaign=buffer. 2020/04/17.

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