Research into the bowhead whale's genetic makeup has identified a protein that may contribute to its resistance to cancer and its extended lifespan. This discovery, detailed in the journal Nature, is part of a broader scientific effort to understand how long-lived, large animals evade cancer.
Peto's Paradox and Cancer Resistance
Peto's paradox observes that larger animals, with a greater number of cells, and long-lived organisms, with more time for genetic mutations, do not necessarily exhibit higher rates of cancer compared to smaller, shorter-lived species. This suggests that these animals have evolved enhanced mechanisms for cancer protection.
Vera Gorbunova, a biologist at the University of Rochester, and her team, investigated the bowhead whale, known for living over 200 years. Their findings indicate that bowhead whales produce an abundance of a protein that efficiently repairs broken DNA. This mechanism differs from strategies observed in other species.
Bowhead Whale's DNA Repair Mechanism
Unlike elephants, which possess multiple copies of the tumor suppressor gene p53—a protein that triggers cell death or DNA repair in pre-cancerous cells—bowhead whales employ a different approach. Researchers hypothesized that bowhead whales might prevent mutations from accumulating initially, rather than focusing solely on eliminating abnormal cells.
Experiments demonstrated that bowhead whale cells are significantly more efficient at repairing DNA breaks than human cells, maintaining genetic integrity by correctly fusing DNA ends. This capability is attributed, in part, to the protein CIRBP (cold-inducible RNA-binding protein), which is highly expressed in bowhead cells. The gene producing CIRBP is activated by cold environments.
Gorbunova suggests that for an organism living over two centuries, investing in cellular maintenance and damage repair may be more advantageous than a strategy primarily focused on cell elimination.
Research and Potential Applications
To investigate CIRBP's effects, researchers overproduced the protein in human cells, which resulted in improved DNA repair efficiency. Additionally, when fruit flies were engineered to produce high levels of CIRBP, they exhibited increased longevity and enhanced resistance to DNA damage. These results suggest a potential for improving human cellular health by modulating this protein.
The research was facilitated by the Iñupiaq community of Barrow, Alaska, who provided bowhead whale tissue samples. Future applications of this research may include developing clinical methods to slow human cellular mutation accumulation, potentially benefiting communities like the Inuit who face rising cancer rates.
Broader Implications for Cancer Biology
Evolutionary biologists Vincent Lynch and Amy Boddy note that these findings contribute to comparative oncology, the study of cancer across species. They highlight that different species have evolved diverse pathways to achieve longevity and resist cancer, offering insights for human cancer treatment. Boddy also emphasizes the conservation message, stating that protecting species with such unique biological adaptations could provide future benefits to human health.
Researchers anticipate that further mechanisms for cancer resistance remain undiscovered in long-lived animals such as bowhead whales, elephants, bats, and naked mole rats, indicating an ongoing field of study.