Animals do the most amazing things. Read about them in this series by Janaki Lenin.
Every year, close to eight million humans die of cancer – ‘the emperor of all maladies’. Of these, 1,300 Indians die every day. About 95% of cancer can be prevented by improving our lifestyles. That includes staying away from tobacco, maintaining a healthy body weight, and eating enough fruits and vegetables. But a good many people do all the right things and still get cancer from genetic defects.
Elephants, African and Asian, rarely fall prey to cancer. What’s the secret of their ability to shirk off the dreaded disease? American researchers may have found an answer.
Elephants are born weighing 100 kg. They grow to more than 3,000 kg in less than 10 years, a 30-fold increase in cell mass. When cells multiply, there’s a risk of DNA not being copied faithfully. Such a high rate of cell division in a large animal is prone to errors. Since elephants are long-lived, these mutations should accumulate and cause malignant tumours. With such risk factors as body size and age working against them, the world’s largest land animals ought to be dying of cancer all the time.
Richard Peto, a professor of medical statistics and epidemiology, University of Oxford, had observed that simply doesn’t happen. Instead, only a few of these long-lived giants appear to develop cancer. However, animals at the other end of the body-size and age spectrum such as mice and rats are highly prone to cancer. Ever since, this contradiction between size and susceptibility to cancer has become known as Peto’s Paradox.
In 2012, Carlo Maley, an evolutionary oncologist from Arizona State University, gave a talk about Peto’s Paradox at a conference of evolutionary medicine and epidemiology in Washington, D.C. He had found that elephants had 20 copies of a gene called TP53 that produce p53, a protein crucial for suppressing tumours.
This protein is like a fact-checker, examining newly formed cells and verifying if they have correct DNA copies. If any are corrupted, it either attempts to repair or gives the command for the cells to commit suicide. If it didn’t give these instructions, the cells would turn cancerous. The protein is so crucial to our well-being that David Lane, a British cancer biologist and one of the discoverers of p53, called it the ‘guardian of the genome’.
Humans have one copy of TP53. Every gene has two alleles. Both of them have to be in working order to prevent cancer. When people inherit only one functional allele of TP53, they have Li-Fraumeni Syndrome (LFS), which leaves them with a 90% risk of getting cancer.
Do multiple copies of the DNA fact-checking gene shield elephants from cancer?
In the audience, listening to Maley was Joshua Schiffman, a paediatric oncologist at Huntsman Cancer Institute and University of Utah School of Medicine, Salt Lake City. Schiffman, who treated patients genetically predisposed to cancer, was especially interested in the elephants’ adaptation. He collaborated with Maley and 11 other colleagues to investigate the role of p53 in cancer prevention. The research team took white blood cells from eight zoo elephants, 11 normal humans with no family history of cancer, and 10 patients suffering from LFS. It tested how the cells responded when their DNA was damaged.
Cells of people with LFS were not as sensitive to damage as normal human cells. In fact, they were less than half as sensitive. Their p53 was too weak to order the destruction of cells, and therefore had a higher chance of turning cancerous.