Reece Davidoff
514
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Peto's Paradox: Cancer's Evolutionary Enigma

— Reece Davidoff

The first known case of cancer was found in duck-billed dinosaur fossils from around seven million years ago. Only a few decades ago, scientists discovered that cancerous cells are created by errors in DNA, called mutations, and that every time a cell divides, there’s a tiny chance a cancerous cell is created. Robert Peto, a cancer researcher, saw this and asked a simple yet powerful question: if each cell division has a tiny chance of creating a cancerous cell, shouldn’t larger animals with 100 times more cells than us—and therefore 100 times more chances to get cancer—have giant tumors by now? 

Researchers have calculated that by age 80, 100% of blue whales should have cancer. In reality, however, whales and other large animals have the same amount or even less cancerous cells than humans. This is known as Peto’s Paradox, and tells us that somehow big animals are 100 times better at fighting cancer than us.

So far, we know how one animal does it: the elephant. Elephants were found to have twenty times more copies of a gene called p53 than humans, which codes for a protein that identifies mutated or damaged DNA in cells and prompts those cells to fix themselves or self-destruct. This means that elephants kill mutated cells at a much higher rate than humans, often destroying cancerous cells before they can reproduce. 

Applying this discovery, scientists inserted extra copies of p53 into the DNA of seventeen mice who were observed throughout their entire lives. These mice were shown to get significantly less cancer than regular mice, which raised hopes for a potential p53 vaccine that could add more copies of the gene to the human genome and possibly reduce the risk of getting cancer. While promising, more research has to be done before this vaccine can be tested in a safe and responsible way. And even if it doesn’t work out, there are still other large animals with different keys to fighting cancer hidden beneath their skin. The secrets to curing cancer may be sitting right outside our doors, grazing on the savannah or swimming in the sea. All we have to do is go out and discover them.


References

Withrow, S. (2020, July 16). A short history of animal cancer. Flint Animal Cancer Center. Retrieved April 15, 2023, from https://www.csuanimalcancercenter.org/2018/11/08/history-of-animal-cancer/ 

Maley, C. (2016, May 21). How nature has already beat cancer. YouTube. Retrieved April 15, 2023, from https://www.youtube.com/watch?v=BQV5F2tlIZE 

Caulin, A. F., & Maley, C. C. (2011). Peto’s Paradox: evolution’s prescription for cancer prevention. Trends in ecology & evolution, 26(4), 175–182. https://doi.org/10.1016/j.tree.2011.01.002

Zhan, C. (2021, January 25). Unlocking Peto’s paradox. Berkeley Scientific Journal. Retrieved April 15, 2023, from https://escholarship.org/uc/item/1fj293bk 

Cunningham, A. (2019, August 8). A resurrected gene may protect elephants from cancer. Science News. Retrieved April 15, 2023, from https://www.sciencenews.org/article/resurrected-gene-may-protect-elephants-cancer 

Callier, V. (2019). Solving Peto’s paradox to better understand cancer. Proceedings of the National Academy of Sciences, 116(6), 1825–1828. https://doi.org/10.1073/pnas.1821517116 

García-Cao, I., García-Cao, M., Martín-Caballero, J., Criado, L. M., Klatt, P., Flores, J. M., Weill, J.-C., Blasco, M. A., & Serrano, M. (2002). ‘super p53’ mice exhibit enhanced DNA damage response, are tumor resistant and age normally. The EMBO Journal, 21(22), 6225–6235. https://doi.org/10.1093/emboj/cdf595 

Sulak, M., Fong, L., Mika, K., Chigurupati, S., Yon, L., Mongan, N. P., Emes, R. D., & Lynch, V. J. (2016). TP53 copy number expansion is associated with the evolution of increased body size and an enhanced DNA damage response in elephants. eLife, 5. https://doi.org/10.7554/elife.11994