A new American study has revealed that the reason elephants rarely get cancer is a special mechanism in their cells that battles the disease.
The study, led by researchers from the Huntsman Cancer Institute at the University of Utah and published last week in the Journal of the American Medical Association, found that elephants have 40 copies of a gene known as P53, a well-known tumor suppressor, while humans have only two. The gene’s intensive activity kills a substantial number of cancer cells in elephants, allowing them to overcome the disease.
Based on these findings, researchers at the Technion-Israel Institute of Technology in Haifa are conducting a follow-up study in an effort to translate the discovery into innovative cancer treatments.
The American study got heavy coverage in the world media – not least because elephants are not usually associated with cancer research. But Prof. Avi Schroeder, of the Technion’s chemical engineering department, insists there is no gimmick here. Schroeder, who is leading the Israeli study, is convinced that this is a serious new avenue for the development of cancer drugs.
Elephants are not as strange a subject for cancer research as one might think. They can reach 70 years of age and have around 100 times as many cells in their bodies as humans; this means they have far more cell divisions going on in their bodies than people do, which theoretically puts them at higher risk for the genetic mutations that cause many types of cancer. But in fact, less than 5 percent of elephants die from cancer, compared to a human cancer mortality rate of between 11 percent and 25 percent.
According to Dr. Joshua Schiffman, M.D., pediatric oncologist at Huntsman Cancer Institute, University of Utah School of Medicine, who led the U.S. study, logic would dictate that elephants develop cancer so often that they would be extinct by now, but that is not the case.
“Nature has already figured out how to prevent cancer. It’s up to us to learn how different animals tackle the problem so we can adapt those strategies to prevent cancer in people,” Schiffman said.
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. The P53 gene was discovered in the 1970s, and Israeli scientists played a significant role in discovering, characterizing, and understanding its role as a cancer inhibitor. One of the first labs to discover the protein was that of Prof. Varda Rotter of the Weizmann Institute of Science in Rehovot, and in 1983, Prof. Moshe Oren, also of the Weizmann Institute, was one of the first scientists to clone the gene. The gene’s anti-cancer properties were identified in 1989.
When the gene is activated in humans, it enters the cell nucleus and represses the cancer mechanisms in two ways: By trying to repair the reproductive process of the DNA that was damaged, or by sparking a process that kills off the damaged cell. One early researcher of the gene called it the genome guardian, and in subsequent studies it emerged that mutant versions of it are found in half of all cancers.
According to the study, elephants have particularly aggressive versions of the gene. “Compared to humans, in elephants the gene works differently,” explained Schroeder. “In elephants the gene doesn’t give the cell a second chance; the moment cancerous activity is detected it kills off the cell without trying to repair it. And indeed, we see that in humans the repair mechanism is often not sufficient and the cancer cell relapses.”
Schiffman was spurred to conduct his research when someone at a scientific conference happened to mention that elephants don’t get cancer. “He tried to get elephant blood through ‘the usual channels’ – scientific institutions, but didn’t succeed,” said Schroeder. Then, during a trip to Salt Lake City’s Hogle Zoo with his children, he saw an elephant performance, during which one of the handlers told the audience that they draw blood regularly from the elephants’ ears to monitor their health. Thus was born the cooperative relationship between the zoo and Schiffman’s lab, which has since broadened to include zoos in other areas.
Around four months ago, Schiffman visited Israel for a pediatric oncology conference that took place at Rambam Medical Center in Haifa. Schiffman discussed his findings at the conference where Schroeder also made a presentation. “As I was listening to his lecture I made a note to myself that I had to meet him,” said Schroeder. It turned out that the feeling was mutual. That’s how the Israeli connection was forged that has resulted in the Technion’s follow-up research. “It was clear to me that we had to take the basic understanding that emerged from the research and develop it into something that can save lives,” Schroeder said.
Schroeder himself is at the forefront of research that combines engineering and medicine, with an emphasis on integrating nanotechnology and targeted drugs. He did his post-doctoral work under Prof. Bob Langer at the Massachusetts Institute of Technology and has since been working on developing nanometric platforms for aiming anti-cancer drugs at targeted cells in the body.
“The biggest challenge in dealing with cancerous growths is the metastases,” he said. “These are tiny, unexpected and fast-spreading, and they attack a patient whose immune system is already weakened by the initial tumor. The miniscule platforms that we are developing here know how to identify diseased tissue and release the drug they are carrying to the precise location.”
Schroeder and his team want to take Schiffman’s research to the next level. Together with a variety of other Technion researchers, among them engineers, chemists, biotechnologists and biomedical experts, he wants to translate the elephants’ defense mechanisms into a cancer drug.
“We will produce the proteins and focus them on diseased cells using nano-cell systems, first in computer models of the disease and later on in people,” he said. “The goal is to create a new treatment and a new treatment approach. The P53 is one of the most important mechanisms in cancer and it’s relevant to almost all types of cancer. We hope that we have here a harbinger of a new treatment.”
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