Attempts to understand cancer without considering natural selection and evolution are “pretty hopeless,” Ewald said.
One problem with the physiological-aging model is how to explain cancers in young people, Dr Ewald said.
“A lot of cancers occur before the end of reproductive lifespans,” he noted. And cancer risk tends to plateau in our 60s and 70s, he added. “If it were really just senescence, you’d expect risk to continue to go up.”
Dr DeGregori and others have argued that at least for the most common type of childhood cancer, acute lymphoblastic leukemia (ALL), the answer likely involves children’s higher rates of cellular division and their smaller initial populations of hematologic stem cells.6 Together, these conspire to amplify the probability that chance mutations will survive and thrive, they reason.
But for ALL—and perhaps most cancer types—Dr Ewald and others suspect another evolutionary culprit: viruses that have been exquisitely honed by natural selection over deep time to overcome host immune defenses and, incidentally, to break down hosts’ cellular barriers to oncogenesis like apoptosis (programmed cell suicide).
“Viruses are getting in there and compromising the function of proteins that pose barriers to cancer, in very sophisticated ways,” Dr Ewald said.
Dr Ewald and his colleague, Holly Swain Ewald, predict that viruses will be found to play a role in manipulating immune checkpoint molecules like programmed death-ligand 1 (PD-L1) to evade immune attack. PD-L1 is a major emerging target for anticancer immunotherapies.
About 20% of all human cancers are already known to involve infectious risk factors, Dr Ewald said.
“We discovered the most conspicuous examples first,” many years ago, he noted. More cryptic infections will require newer tools like next-generation whole-genome sequencing, Dr Ewald believes, noting that Mel Greaves and others have suspected a viral culprit for ALL for decades, though the tools for detecting cryptic infections have only recently been developed.
What’s more, viral carcinogenesis could work in concert with chemicals or chemical mixtures like tobacco smoke, which are known to be carcinogenic. These chemicals can be not only mutagenic but immunosuppressive, he noted.
“Health science is so good at dealing with infections,” Dr Ewald noted. “We should exhaust the possibility that chronic disease is caused by infections; we should really test those exhaustively. Then, if we exhaust that possibility, we can look elsewhere. Our potential success is so much better if something’s caused by infection.”