A few extra copies of p53 and we could also suppress cancerous tumours

Elephants should get cancer 100 times more often than humans but instead they have a cancer mortality rate which is at 20-50% of the rate in humans. Cell for cell therefore, elephants are 200 to 500 times less likely to develop cancer than humans. Genetic studies may have revealed why that is so. They have 38 additional copies of a tumor suppressing gene (p53) while humans have only two.

Sounds fascinating. If we could only ingest some additional copies of a specific genes, of which humans have only two, we may be able to suppress cancerous tumours.

Wikipedia tells me that

Tumor protein p53, also known as p53, ……. is any isoform of a protein encoded by homologous genes in various organisms, such as TP53 (humans) and Trp53 (mice). …. p53 has been described as “the guardian of the genome” because of its role in conserving stability by preventing genome mutation. ….. The International Cancer Genome Consortium has established that the TP53 gene is the most frequently mutated gene (>50%) in human cancer, indicating that the TP53 gene plays a crucial role in preventing cancer formation. TP53 gene encodes proteins that bind to DNA and regulate gene expression to prevent mutations of the genome.

Now a new paper reports a study on why elephants rarely get cancers and finds that elephants have 38 copies of p53 whereas humans have only two.

Press Release Huntsman Cancer Institute:

Why Elephants rarely get cancer

…. elephants have 38 additional modified copies (alleles) of a gene that encodes p53, a well-defined tumor suppressor, as compared to humans, who have only two. Further, elephants may have a more robust mechanism for killing damaged cells that are at risk for becoming cancerous. In isolated elephant cells, this activity is doubled compared to healthy human cells, and five times that of cells from patients with Li-Fraumeni Syndrome, who have only one working copy of p53 and more than a 90 percent lifetime cancer risk in children and adults. The results suggest extra p53 could explain elephants’ enhanced resistance to cancer.

Joshua D. Schiffman, MD et al. Potential mechanisms for cancer resistance in elephants and comparative cellular response to DNA damage in humans. JAMA, October 2015 DOI:10.1001/jama.2015.13134

According to Schiffman, elephants have long been considered a walking conundrum. Because they have 100 times as many cells as people, they should be 100 times more likely to have a cell slip into a cancerous state and trigger the disease over their long life span of 50 to 70 years. And yet it’s believed that elephants get cancer less often, a theory confirmed in this study. Analysis of a large database of elephant deaths estimates a cancer mortality rate of less than 5 percent compared to 11 to 25 percent in people.

In search of an explanation, the scientists combed through the African elephant genome and found at least 40 copies of genes that code for p53, a protein well known for its cancer-inhibiting properties. DNA analysis provides clues as to why elephants have so many copies, a substantial increase over the two found in humans. A substantial majority, 38 of them, are so-called retrogenes, modified duplicates that have been churned out over evolutionary time.  

Schiffman’s team collaborated with Utah’s Hogle Zoo and Ringling Bros. Center for Elephant Conservation to test whether the extra gene copies may protect elephants from cancer. They extracted white blood cells from blood drawn from the animals during routine wellness checks and subjected the cells to treatments that damage DNA, a cancer trigger. In response, the cells reacted to damage with a characteristic p53-mediated response: they committed suicide.

“It’s as if the elephants said, ‘It’s so important that we don’t get cancer, we’re going to kill this cell and start over fresh,’” says Schiffman. “If you kill the damaged cell, it’s gone, and it can’t turn into cancer.  This may be more effective of an approach to cancer prevention than trying to stop a mutated cell from dividing and not being able to completely repair itself.”

I don’t understand any of this but can imagine that in a 100 years or so, children will routinely be given “genetic p53 shots”  — as routinely as they get vaccinations today. It’s not as if we don’t already have the gene. So just arranging a few extra copies of a gene we already have, doesn’t sound Frankensteinian and should not lead to developing elephantine features.


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