Bowhead Whales’ Anti-Cancer Superpower

(Cover Illustration by Catherine Xu)

What are bowhead whales?

Bowhead whales are the second largest marine mammals on Earth, weighing over 80,000 kilograms. These massive whales are remarkable not only for their size but also for their lifespan. Living up to 200 years, this marine mammal experiences almost triple that of a human. These long-lived whales reside in subarctic waters, similar to the environment used in human cryotherapy—a therapeutic treatment that uses extreme cold to minimize inflammation and increase metabolism. As bowheads are so large, they have a considerably high number of cells, ranging into the quadrillions.

Large mammals are a key part of a phenomenon called Peto’s Paradox. The genetic pattern shows a surprising trend: it explains how sizable animals are not highly cancer-prone, despite having a substantial number of cells present in their bodies. Elephants are another example of Peto’s Paradox. These intelligent animals have between three and four quadrillion cells in their bodies, creating an elevated risk for those cells to become cancerous. Surprisingly, both these large mammals rarely develop cancer. Initially, whales’ extremely low cancer development rate was attributed to the similarities between their environment and full-body cryotherapy. However, scientists have now begun to explore the genetic advantages these whales possess.

How do genetics play a role in the cause of cancer?

Cancer is caused by an uncontrollable division of mutated cells, which can create masses of cancerous cells known as tumors. Cancer formation begins with a series of genetic mutations. External factors, like UV rays or carcinogens (cancer-causing substances or agents), and internal factors, like replication errors during DNA synthesis, combine to create damaged DNA. Damaged DNA does not code for necessary proteins, leading the body to end lose its cellular functions. Suppose growth enhancer genes are always activated and tumor suppressor genes are inactivated. In that case, cells with mutated or damaged DNA can rapidly duplicate through mitosis (the process in which a cell duplicates itself to reproduce) and create identical copies of themselves. Mutations, which may begin in a few cells, can create a chain reaction with no barriers to stop exponential growth. Eventually, these large masses of mutated cells create what we characterize as tumors. Tumors can grow blood vessels through angiogenesis, allowing cells to continue receiving the nutrients to divide. Eventually, cancerous cells can metastasize, or spread, to different parts of the body. In the event that cancer spreads to other organs, it is considered terminal and almost impossible to treat, which leads to high mortality rates.

What is the genetic difference?

Compared to other organisms, bowhead whales are more accurate and efficient at replacing damaged DNA in cells. Dr. Vera Gorbunova at the University of Rochester conducted a study to prove the profound impact of this species’ molecular differences. Researchers used an enzyme (a protein that can catalyze or speed up reactions) to induce double-strand breaks; the structure of DNA is a double helix and has two strands, which are broken apart in instances of these breaks. Researchers induced the experimental breaks in the DNA of humans, cows, mice, and bowhead whales, then prompted its repair. The repaired genes were tracked with a fluorescent green protein. If the cell repaired the DNA accurately, the DNA was scanned as a fluorescent green. Miraculously, whale cells repaired twice as many cells as other species without deleting any base pairs.

Bowhead whale connective tissue undergoes genetic changes similar to the function of tumor suppressors, allowing their cells to repair double-strand breaks with high efficiency and accuracy. These cells have a significantly increased ability to mend DNA damage that may lead to cancer-causing genetic mutations. Their enhancements cause increased expression of the p53 gene, which in turn causes the levels of two proteins, CIRBP and RPA2, to surge. In humans, these proteins increase the efficiency of DNA repair. The elevated expression of CIRBP protein in the whale is believed to be due to the physiological stresses endured in the arctic, ultracold temperatures. The exact mechanisms of how cryotherapy enhances gene repair are currently under investigation but are indicated to be extremely impactful. However, since humans also have this “cancer-suppressor” gene, there can be potential applications for understanding how increasing the expression of these may increase DNA repair efficiency in humans.

How can this be used in human healthcare?

Studies suggest that rather than different genes in bowhead whales that decrease rates of oncogenesis, this “cancer suppressor gene” is only an enhancement of genes already present in humans. Our bodies can overexpress p53 to grow levels of CIRBP and RPA2 to enhance the accuracy of DNA repair, thereby reducing the occurrence of cancer. Dr. Gorbunova tested this proposed theory and found that when human and mouse cell levels of CIRBP proteins are manually increased, cells repair double-strand breaks at double efficiency levels. This finding sparks hope in the search to find potential treatments for human cancer in the future, creating a new methodology of cancer prevention starting at the root cause. These bowhead whales have a superpower that gives them the ability to repair DNA more accurately and, therefore, have significantly lower rates of cancer development. With this new research, humans might also have this superpower one day.

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