The rarity of cancer in elephants can help explain the disease in humans

Elephants have 100 times more cells than humans. But they rarely have cancer. This is surprising because cancer is the result of cell division that has gone awry, and the larger the cells of an organism, the greater the chance that certain cells will turn into tumors. In addition, because elephants live so long – between 60 and 70 years – their cells have more opportunities to mutate.

The counter-intuitive observation that the risk of cancer is not always correlated with a species. The size or longevity is known as Peto's Paradox, named after the British epidemiologist Richard Peto, who noted the phenomenon in 1977. It turns out that cancer does not strike all species equally: Some animals have developed powerful strategies to control the disease. others are particularly vulnerable.

Scientists are increasingly exploring this interspecific variation in cancer rates, hoping to learn more about how cancer works in humans and identify better ways to treat or prevent it. the time, "said Joshua Schiffman, cancer researcher at the University of Utah, who has been studying the subject for about ten years." But they do not, they have developed really effective anti-cancer strategies. "

Schiffman – a pediatric oncologist who also treats humans with cancer – and his colleagues found that elephants have 40 copies of the TP53 gene, which suppresses tumor cells before they In comparison, humans and most other animals have only two copies

Schiffman and his research partner Carlo Maley of Arizona State University say that "no one can see it." they suspect that extra copies can give elephants a powerful ability to keep mutant cells at bay.Scientists have long known that TP53 helps the body kill malignant cells before they get infected. Although until the work of Schiffman and Maley, no one realized that one animal had 40 copies of the gene. The approach of elephants seems to be a unique evolutionary strategy to fight cancer

Schiffman and his colleagues discovered that elephants also have other anticancer mechanisms. Elephant cells react differently when they are exposed to substances that damage the DNA. Instead of trying to repair the damage, they tend to simply die. With cancer, it is a much safer approach: cells that try to heal themselves are more likely to mutate and then turn into cancer cells. In an article published in March, Schiffman and the University of Utah, scientist Christopher Gregg, identified three genes that prevent mutations by promoting DNA repair

Together, these Genetic adjustments can give elephants several weapons against the disease. single animal with abnormally low rates of cancer. Using data from zoos and veterinarians as well as anecdotal reports from wild and laboratory research, scientists know or suspect that other creatures, including mole rats, gray squirrels, horses, whales and bats, rarely have cancer

. clear where humans fall on the spectrum of risk. For humans, the lifetime probability of cancer is about 50%. Although we have cancer suppressor genes, we also tend to live relatively long lives. For most animals, the risk of cancer is probably between 20 and 40%, with outliers at each end – elephants on one side and dogs, mice and cheetahs on the other.

Of course, cancer is followed much more systematically. than in other species. "We do not have a lot of data from nature," said University of California Riverside biologist Leonard Nunney, who studies evolution, animals and cancer, and coined the term "Peto's Paradox". "So it's very difficult to compare."

The strangest animal studied for its ability to fight cancer is the naked mole rat, a pink, hairless, five-inch-long rodent that lives in burrows. in East Africa. These creatures survive much longer than most rodents – up to age 32 – and rarely have tumors.

For decades, scientists have been studying thousands of mole rats in laboratories and zoos around the world. during this time, they documented only six cases of cancer. Over the last 13 years, scientists from the University of Rochester Vera Gorbunova and her husband, Andrei Seluanov, have been trying to understand how animals accomplish this.

A key can be a viscous liquid known as hyaluronic acid. Gorbunova and Seluanov discovered that animals produce large quantities of this substance, which seems to prevent tumors from becoming uncontrollable. The mechanism may involve contact inhibition, the tendency of cells to stop dividing when they are pressed tightly by other cells. Cancer begins when mutated cells grow uncontrollably; By increasing contact inhibition, hyaluronic acid, which Gorbunova describes as "essentially a sticky sugar," probably prevents these tumor cells from replicating.

Naked mole rats also have other mechanisms to block cancer. The animals have an unusually powerful version of a gene called p16, which prevents the growth of tumor cells, and have also developed an additional strategy: If the cancer cells exceed hyaluronic acid and p16, the cells of the rats moles have a safety switch that causes tumors to turn off essentially, a condition known as senescence.

Gorbunova and Seluanov also study blind mole rats, another rodent species with extremely low rates of cancer. During decades of research on hundreds of these animals, scientists have never found a natural tumor. These creatures, who live underground and do not have eyes, have developed an anti-cancer strategy known as concerted cell death. Their cells are programmed to reproduce far fewer times than those of most other species, a feature that dramatically reduces the chance that mutations will go crazy.

Other researchers examining some species of bats have located several tumor suppressor genes. A recent study of the bowhead whale, which weighs up to 100 tons and can live more than 200 years, has identified several genes that likely enhance the creature's ability to repair DNA mutations. Slowing the metabolism of large animals such as elephants and whales may also play a role in their lower cancer rates: more intense energy production leads to greater cell division and thus increased risk of mutations.

Just as some creatures are more apt at repelling tumors, others are especially vulnerable. Some dog breeds fall into this category: More than half of all golden retrievers die of cancer; Scottish terriers are 18 times more likely than average dogs to have bladder cancer, and Irish wolf dogs are 100 times more likely to have bone cancer.

This predisposition is largely due to the low level of genetic variation of most breeds. known as the founder effect. As inbreeding has increased over generations, genetic abnormalities in the initial population have been magnified

. This predisposition makes animals a valuable model. "With dogs, it's much easier to find genetic aberrations that lead to cancer," said Matthew Breen, molecular biologist from the North Carolina State University, who has studied canine cancer since more than two decades. "We can speed up the discovery process."

He discovered that certain types of cancer develop along very similar pathways in dogs and humans, and identified several genetic mutations in dog cancers that appear to exist in human versions. Cancer. One of these mutations, which plays a role in 85% of cancers of the canine bladder, also exists in humans. Scientists knew about human mutation, but Breen's research offers a key clue to its potential significance.

This work is particularly useful for cancers that are rare in humans. Take bone cancer: In the United States, about 1,000 people a year, mostly children, become sick. In comparison, more than 50,000 dogs are diagnosed each year. Breen and his colleagues began to identify what motivates the disease in dogs and showed that the same mutations are present in the human version. "By working with dogs, we have access to 50 times more patients," he said. "This gives us a much better chance of understanding the mechanics of this."

Breen oversees a national study that monitors millions of dogs. He travels constantly, in contact with veterinarians, dog owners and breeders, asking them to share data on canine cancer. The potential reservoir is huge: every year, more than 4 million dogs in the United States are diagnosed with cancer. Finally, he said, the database will allow scientists to delve deeper into how, why and where dogs have cancer.

The ultimate goal is to develop new ways to fight human cancer. Finally, it may be possible to use gene therapy, genetic engineering or pharmacology to implement cancer control strategies in humans. This work has already begun: Gorbunova and Seluanov are now testing whether hyaluronic acid can prevent disease in mice. Other animal anti-cancer strategies have not reached the test stage, but Schiffman said the potential is clearly there.

"It's a whole new field," he said. "We are at the forefront of the iceberg, nature has proposed these solutions over the course of hundreds of millions of years of evolution, and now we must analyze this and apply it to humans . "

– The Washington Post