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https://www.telegraphindia.com/1151009/jsp/nation/story_47017.jsp

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An Indian cancer biologist in the US who grew up in Chennai loving organic chemistry and mathematics has helped resolve a puzzle that had baffled scientists for decades: the rarity of cancer in elephants.

Srividya Bhaskara, a principal investigator at the Huntsman Cancer Institute at the University of Utah, is part of a research team that has found that elephants have 38 additional copies of a gene that codes for a tumour suppressor protein called p53.

Humans, in contrast, have two copies of p53. The team’s experiments suggest that the additional copies of p53 give elephants a far more robust mechanism to kill damaged cells that may turn cancerous than similar cellular machinery available in humans.

The rarity of cancer among elephants, despite their life spans ranging between 50 and 70 years, has been a puzzle because their large body size and rapid growth while they are young should increase the frequency of cancer as they grow and age.

Some biologists compute that such a cancer risk should have caused elephants to go extinct.

“At the rate of cell division we see, young elephants should be getting cancer and dying before they even get a chance to reproduce,” Joshua Schiffman, a paediatric oncologist at the Huntsman Cancer Institute who led the research, told The Telegraph over the phone.

However, the researchers, who analysed a database of over 600 elephants maintained by an elephant-keeper in Sweden, found that only about five per cent of the elephants had been documented as dying from cancer compared with about 11 to 25 per cent of humans.

The study’s findings appeared today in the Journal of the American Medical Association.

The p53, discovered 35 years ago, has long been known to suppress tumours by signalling cells that have acquired genetic damage to commit apoptosis, or cellular suicide. The p53 gene is mutated or inactivated in breast, liver, lung, ovarian and colon cancers, among others.

Now, the Utah researchers have found that elephant cells subjected to genetic damage are pushed towards apoptosis far more aggressively than human cells with similar genetic damage.

Bhaskara, independently involved in research aimed at developing new drugs for chemotherapy, helped design some of the experiments on elephant cells, sharing her expertise on biological repair mechanisms involving genetic material.

The scientists found that elephant cells self-destructed at twice the rate of healthy human cells and more than five times the rate of cells from people with a condition called Li-Fraumeni, who have only one copy of p53 and thus are at high risk of developing cancer.

“This is a discovery,” Renu Wadhwa, head of the cell proliferation research group at the National Institute of Advanced Industrial Science and Technology in Japan, who was not associated with the Utah research, said over the phone.

“These findings suggest that elephants have very strong tumour suppressor mechanisms. Through the extra copies of the gene, elephants are securing this mechanism.”

But scientists have cautioned that more research would be needed to fully understand the mechanisms in play in elephants. Earlier studies in mice had shown that extra copies of p53 could accelerate ageing.

“It is possible that elephants have some compensatory genetic mechanisms that prevent the premature ageing observed in mice with extra p53,” said Sanjeev Das, a senior scientist at the National Institute of Immunology, New Delhi, who has been independently studying p53 mechanisms in cancer.

What is your educational background? How did you end up in such an offbeat, unconventional and uncommon career?

Bhaskara, who completed school and university in Chennai at Mohammad Sathak College of Arts and Science, University of Madras, before moving to the US for research, recalls wanting to study organic chemistry and mathematics while in high school but later switching to biochemistry in university. She did her Phd at Department of Biochemistry, Cellular and Molecular Biology, University of Tennessee and PostDoc at Vanderbilt University Medical Center (Biochemistry).

“Mathematics is theoretical,” she said in a phone interview. “But biochemistry is lab work — and I’m doing just that.”

The Utah scientists are hoping to use their findings to test large numbers of natural or synthetic compounds on cancer cells.

“We want to determine if any compound can mimic, in cells exposed to genetic damage, the effect of the extra p53 we see in elephant cells,” Schiffman said. “The long-term goal is to apply such knowledge on patients.”