Cosmologists propose new theories on the origin of diseases

Paul Davies, a cosmologist at Arizona State University, and his colleagues have proposed a controversial conclusion: cancer is a trial run of a "safe mode" by human cells, much like a computer system tries to protect itself when faced with an external threat.

This theory is primarily based on the evolution of cancer, and if the theory is correct, their model suggests that some unconventional therapies, such as oxygen therapy, viral or bacterial infections, may be particularly effective.

Does cancer arise from the body's cells testing a "safe mode," much like a damaged computer system trying to protect itself from external threats? This is the conclusion reached by Paul Davies, a cosmologist at Arizona State University, and his colleagues, who have proposed a new and controversial theory of cancer's origin. This theory is primarily based on the evolutionary roots of cancer. If this theory is correct, their model suggests that oxygen therapy and some unconventional treatments involving viral or bacterial infections may be particularly effective.

At first glance, Davies doesn't seem like a warrior in the "war on cancer"—he has a background in physics, not biomedicine. But about seven years ago, he was invited to establish a new institution in Arizona—one of 12 funded by the National Cancer Institute—to bring together physicists and oncologists to discover new perspectives on the disease. "We were asked to rethink cancer from the top down," Davies says.

Subsequently, Davies collaborated with Charley Lineweaver, an astrobiologist at the Australian National University, and Mark Vincent, an oncologist at the London Health Sciences Centre, to propose a "reversion" model, positioning cancer as a re-expression of ancient "pre-programmed" traits. In a new study published last month in the *Proceedings of the Biology Journal*, the research team pointed out that because cancer appears in many animals, plants, and humans, it must have evolved from millions of years ago when organisms shared a common single-celled ancestor.

Back then, cells benefited from immortality, or the ability to proliferate indefinitely, as cancer does. But as complex multicellular organisms began to emerge, "'immortality' was delegated to eggs and sperm," Davies says, adding that somatic cells, which are not involved in reproduction, no longer needed this ability.

The research team hypothesizes that when healthy cells face environmental threats, such as radiation or lifestyle factors, they can revert to a "pre-programmed safety mode." In this mode, cells abandon higher functions and switch their dormant capabilities to proliferative ones in order to survive. "Cancer is an automatic defense mechanism," Davies noted, "and once this subroutine is triggered, it coldly executes itself."

On September 11, at a medical engineering conference held at Imperial College London, Davies described a series of cancer therapies based on this atavistic phenomenon. Davies pointed out that instead of simply attacking cancer's ability to replicate, this model reveals "cancer's Achilles' heel." For example, if the theory is correct, then the Earth's environment was more acidic and oxygen-scarce in the early stages of cancer evolution. Therefore, researchers predict that utilizing high levels of oxygen and adding reducing sugars to the diet to reduce acidity could inhibit tumors and induce tumor shrinkage.

Costantino Balestra, a physiologist at the Free University of Brussels in Belgium, stated that the use of oxygen to treat cancer has been independently studied for many years and appears to support Davies's viewpoint. In a peer-reviewed but unpublished paper, Balestra and colleagues demonstrated that a slight increase in oxygen levels can begin to induce death in leukemia cells without harming healthy cells.

“It seems too simple,” Balestra said. “Our preliminary results appear to suggest that providing one to two hours of extra oxygen per day, in combination with other conventional cancer treatments, would benefit patients without serious side effects.” Balestra emphasized, however, that the study did not test Davies’ hypothesis and cannot be considered evidence of the correctness of the atavistic model.

Furthermore, Davies and colleagues are proponents of immunotherapy, particularly the selective infection of patients with viruses or bacteria. Researchers have investigated the anticipated effects of this therapy, which artificially stimulates a patient's immune system. For example, immunotherapy has been well-received for treating melanoma, and its effectiveness against other cancers is being studied.

However, Davies also mentioned that, according to the atavism model, in addition to stimulating the immune system, cancer cells may be more susceptible to pathogens and killed than healthy cells because they lose their enhanced protective function when they restart "safe mode".

However, some scientists, including David Gorski, an oncology surgeon at Wayne State University in Michigan, are skeptical. "Atavism predictions are meaningless; scientists haven't proposed it through other avenues," he said.

Davies and his colleagues have begun to test their theory more directly to address the doubts. Davies explains, "The key to our theory is considering the age of cancer genes." The atavism model shows that in the early stages of cancer, cells can revert to a more primitive model, and the most recently evolved functions are shut down. The research team therefore predicts that during cancer development, the most recently evolved genes will lose function, while older genes will be activated.

To test the hypothesis, Davies' team cross-referenced current cancer genome atlas data with databases of various gene taxa. This data helps biologists trace the age of genes. Any correlation between gene age and cancer would support atavistic models. "This data has never been aggregated before, but data mining is crucial, and that's what we're currently doing," Davies said.

Brendon Coventry, a surgical oncologist and immunotherapist at the University of Adelaide in Australia, sees the value in the research of physicists and oncologists who are piecing together existing medical evidence in an attempt to understand the origins of cancer. “The enormous financial and intellectual resources invested in biology and medicine haven’t yielded major breakthroughs in the conventional fight against cancer; perhaps it’s time for a new perspective,” Coventry says. “A cosmologist could view the cell as an ‘inner universe’ and explore it using new methods.”