Why Us and not the Elephants?

Timothy L. Cannon, MD, is board certified in medical oncology, hematology and internal medicine. His specialty is managing gastrointestinal cancers. Dr. Cannon emphasizes personalized care for his patients and is interested in pharmacogenomics as well as using technology to improve patients’ access to care. Read Dr. Cannon’s profile.

Researchers at the University of Utah asked, on behalf of the entire human race, “Why us?”

They posed this question in regards to our much higher incidence of cancer compared to large mammals such as the elephant. Based on their data, the lifetime risk of cancer in an elephant is less than five percent, compared to approximately 20 percent for humans. This finding is counterintuitive because:

• Elephants have 100 times as many cells as humans, giving them more opportunity to accumulate cancer-causing mutations.
• Their average life span is approximately as long as humans.

The Elephant Experiment:

Their results were published this month in the Journal of the American Medical Association (JAMA). To conduct the experiment:

1. Researchers collected necropsy (animal autopsy) data compiled by the San Diego Zoo to calculate the life expectancy and cancer incidence of elephants.
2. After finding a similar life span to humans, but lower cancer rate, they conducted a genomic analysis of oncogenes and tumor suppressors from both African and Asian elephants.
3. The scientists treated peripheral mononuclear blood cells and fibroblasts from elephants and humans with DNA-damaging agents, to investigate how the cells would react. Specifically, they used ionizing radiation and doxorubicin.

The Results:

The findings:

• Elephants have a markedly lower cancer rate then humans despite their higher cellular mass.
• Elephants have 20 copies of a powerful tumor suppressor gene called TP53, while humans only have one copy.
• When exposed to DNA-damaging agents, elephant cells undergo apoptosis (cell death) quickly, so the cancer-promoting mutations cannot grow and spread. In human cells, damaging mutations propagate (multiply) quickly. The effect is even more pronounced in people with Li-Fraumeni syndrome (meaning one of two TP53 genes are mutated).

What Do These Results Mean?

Presumably, elephants’ lower cancer rate is a result of natural selection. Elephants reproduce throughout their life span, even into their 60s and 70s. According to anthropologists, elderly males have an elevated status, which increases their reproductive opportunities at an older age.

Perhaps this reproductive norm necessitated a more efficient means of cancer suppression. The authors note that both African and Asian elephants have 20 copies of TP53, suggesting that this cancer suppression ability existed prior to their divergence more than 6 million years ago. Perhaps humans will have similar luck, if our species exists several million years from now.

Improving Cancer Care

So, can we use this knowledge to improve cancer care? The promise of using viral vectors (tools to deliver genetic material into cells) to insert functional TP53 genes into the cancer cells is not a new idea. However, it is not an easy task.

There are ongoing studies in this field in lung cancer and other cancers. Perhaps the findings of these scientists will give us new insight into the potential of this treatment. From my perspective, the human (and elephant) interest aspect of this piece stands alone. Kudos to the scientific team for exploring the 35-year-old question dubbed “Peto’s paradox”: why large mammals with more cells don’t have a higher incidence of cancer.