Peto's paradox and cancer cure: what can we learn from whales and elephants?

Cancer is a disease of uncontrolled cell growth and division, and the risk of developing cancer increases with the number of cell divisions during the lifetime of an organism. Therefore, one would expect that large and long-lived animals, such as whales and elephants, would have a higher chance of getting cancer than humans. However, this is not the case. In fact, these animals have remarkably low rates of cancer, despite having thousands of times more cells and living much longer than humans. This phenomenon is known as Peto's paradox, named after the epidemiologist Richard Peto who first observed it in 1977.

How do whales and elephants avoid cancer? What mechanisms have they evolved to suppress tumor formation? And can we use this knowledge to develop new strategies for cancer prevention and treatment in humans? These are some of the questions that scientists are trying to answer by studying these amazing animals.

Whales: the giants of the sea

Whales are the largest animals on Earth, with some species reaching up to 30 meters in length and weighing up to 200 tons. They can also live for over 200 years, making them among the longest-lived mammals. Yet, they have a very low incidence of cancer, estimated at less than 5%². How do they achieve this feat?

One possible explanation is that whales have evolved a more efficient DNA repair system, which can fix the errors that occur during cell division and prevent mutations from accumulating. DNA repair is essential for maintaining genomic stability and preventing cancer. Whales may have enhanced their DNA repair capacity by increasing the expression of genes involved in this process, such as BRCA1 and ERCC1.

Another possible explanation is that whales have evolved a more effective way of eliminating damaged or abnormal cells, which could potentially become cancerous. This process is called apoptosis, or programmed cell death, and it is regulated by genes such as p53. Whales may have increased their apoptotic ability by having more copies of the p53 gene, or by having different variants of this gene that are more active or stable.

Elephants: the giants of the land

Elephants are the largest land animals, with some species reaching up to 6 meters in height and weighing up to 6 tons. They can also live for up to 70 years, making them among the longest-lived land mammals. Yet, they have a very low incidence of cancer, estimated at less than 5%. How do they achieve this feat?

One possible explanation is that elephants have evolved a more robust immune system, which can detect and eliminate abnormal or foreign cells, such as cancer cells or pathogens. The immune system is composed of various types of cells and molecules that work together to protect the body from disease. Elephants may have enhanced their immune system by having more copies of genes involved in this process, such as NK-lysin and TRAF3.

Another possible explanation is that elephants have evolved a more powerful way of preventing damaged or abnormal cells from dividing uncontrollably, which could lead to tumor formation. This process is called senescence, or permanent cell cycle arrest, and it is regulated by genes such as p16. Elephants may have increased their senescence ability by having more copies of the p16 gene, or by having different variants of this gene that are more active or stable.

Implications for human health

Peto's paradox reveals that nature has found multiple ways to solve the problem of cancer prevention in large and long-lived animals. By studying these animals, we can gain valuable insights into the molecular mechanisms that underlie cancer resistance and susceptibility. We can also identify potential targets for developing novel therapies or interventions for human cancers.

For example, we can use gene editing tools such as CRISPR-Cas9 to modify our own genes to mimic those of whales or elephants, and enhance our own DNA repair, apoptosis, immune system, or senescence abilities. We can also use drugs or natural compounds that can activate or inhibit these pathways in our cells. We can also use biomarkers or tests that can measure these pathways in our tissues or blood samples, and monitor our risk of developing cancer or our response to treatment.

Peto's paradox shows us that cancer is not inevitable, even for large and long-lived organisms. It also shows us that evolution has provided us with a rich source of inspiration and innovation for finding new ways to fight this disease. By learning from whales and elephants, we may be able to improve our own health and longevity.