“Tumors are a re-emergence of our inner Metazoan 1.0, a throwback to an ancient world when multicellular life was simpler,” says Paul Davies of Arizona State University’s Beyond Center for Fundamental Concepts in Science . “In that sense, cancer is an accident waiting to happen.”
“Cancer is not a random bunch of selfish rogue cells behaving badly, but a highly-efficient pre-programmed response to stress, honed by a long period of evolution,” claims Davies, director of the BEYOND Center for Fundamental Concepts in Science at ASU and principal investigator of a major research program funded by the National Cancer Institute designed to bring insights from physical science to the problem of cancer.
They say it’s because cancer revisits tried-and-tested genetic pathways going back a billion years, to the time when loose collections of cells began cooperating in the lead-up to fully developed multicellular life. Dubbed by the authors “Metazoa 1.0,” these early assemblages fell short of the full cell and organ differentiation associated with modern multicellular organisms – like humans.
But according to Davies and Lineweaver, the genes for the early, looser assemblages – Metazoa 1.0 – are still there, forming an efficient toolkit. Normally it is kept locked, suppressed by the machinery of later genes used for more sophisticated body plans. If something springs the lock, the ancient genes systematically roll out the many traits that make cancer such a resilient form of life – and such a formidable adversary.They turned to cancer research only recently, in part because of the creation at Arizona State University of the Center for the Convergence of Physical Science and Cancer Biology. The center is one of twelve established by the National Cancer Institute to encourage physical scientists to lend their insights into tackling cancer.
The new theory challenges the orthodox view that cancer develops anew in each host by a series of chance mutational accidents. Davies and Lineweaver claim that cancer is actually an organized and systematic response to some sort of stress or physical challenge. It might be triggered by a random accident, they say, but thereafter it more or less predictably unfolds.
Their view of cancer is outlined in the article “Exposing cancer’s deep evolutionary roots,” written by Davies (available free with registration -see below). It appears in a special July issue of Physics World devoted to the physics of cancer.
“We envisage cancer as the execution of an ancient program pre-loaded into the genomes of all cells,” says Davies, an Arizona State University Regents’ Professor in ASU’s College of Liberal Arts and Sciences. “It is rather like Windows defaulting to ‘safe mode’ after suffering an insult of some sort.” As such, he describes cancer as a throwback to an ancestral phenotype.
The new theory predicts that as cancer progresses through more and more malignant stages, it will express genes that are more deeply conserved among multicellular organisms, and so are in some sense more ancient. Davies and Lineweaver are currently testing this prediction by comparing gene expression data from cancer biopsies with phylogenetic trees going back 1.6 billion years.
But if this is the case, then why hasn’t evolution eliminated the ancient cancer subroutine? “Because it fulfills absolutely crucial functions during the early stages of embryo development,” Davies explains. “Genes that are active in the embryo and normally dormant thereafter are found to be switched back on in cancer. These same genes are the ‘ancient’ ones, deep in the tree of multicellular life.”
The link with embryo development has been known to cancer biologists for a long time, says Davies, but the significance of this fact is rarely appreciated. If the new theory is correct, researchers should find that the more malignant stages of cancer will re-express genes from the earliest stages of embryogenesis.
Davies adds that there is already some evidence for this in several experimental studies, including recent research at Harvard University and the Albert Einstein College of Medicine in New York.
“As cancer progresses through its various stages within a single organism, it should be like running the evolutionary and developmental arrows of time backward at high speed,” says Davies. The image belwo shows that a typical four-week-old human embryo looks similar to fish embryos, with proto-gills and a tail.(credit: University of New South Wales).
This could provide clues to future treatments. For example, when life took the momentous step from single cells to multicellular assemblages, Earth had low levels of oxygen. Sure enough, cancer reverts to an ancient form of metabolism called fermentation, which can supply energy with little need for oxygen, although it requires lots of sugar.
Davies and Lineweaver predict that if cancer cells are saturated with oxygen but deprived of sugar, they will become more stressed than healthy cells, slowing them down or even killing them. ASU’s Center for the Convergence of Physical Science and Cancer Biology, of which Davies is principal investigator, is planning a workshop in November to examine the clinical evidence for this.
“Like aging, cancer seems to be a deeply embedded part of the life process," says Davies. "Also like aging, cancer generally cannot be cured but its effects can certainly be mitigated, for example, by delaying onset and extending periods of dormancy. But we will learn to do this effectively only when we better understand cancer, including its place in the great sweep of evolutionary history.”
In the image at the top of the page, the upper row shows a normal breast cell with a smooth nuclear membrane of regular shape. The bottom row shows an aggressive breast cancer cell with a distinctively irregular nucleus and overall shape. The left column shows the whole cell, with the cytoplasm appearing as a gray haze. The middle column shows the naked nuclear membrane and the right column shows density variations in the nuclear DNA. (Image courtesy of Vivek Nandakumar, Center for Biosignatures Discovery Automation, Biodesign Institute, Arizona State University)
Source: Paul Davies, Exposing cancer's deep evolutionary roots, Physics World, 2013 (requires free registration)
The Daily Galaxy via Physics World and Arizona State University