Cancer: The ancient ghost in our genes

Cancer is not an invader. It’s a traitor. It’s a civil war that erupts within the silent, trillion-celled republic of our own bodies. While most diseases attack from the outside or cause our cells to wither and die, cancer does the opposite. It whispers a terrible, seductive secret to our cells: proliferate. And they listen.

This is why our fight against it has been so brutal. We’re not trying to heal cells; we’re trying to kill them. For decades, our primary strategy has been a medieval-sounding gauntlet of “slash, poison, and burn” – surgery, chemotherapy, and radiation. Despite pouring unprecedented fortunes into research, a true cure remains elusive. The frustration is palpable. Visionary specialists like Azra Raza argue we’re stuck in a loop, focused on killing the monster after it’s already grown, instead of figuring out how to stop it from being born in the first place.

To find the solution, we must find the root cause. And to do that, we might need to look not just under a microscope, but deep into the past. Are we even on the right track?

What if cancer isn’t a modern malfunction, but an ancient echo?

This is the mind-bending idea from physicist and biologist Paul Davies and his team. They suggest that cancer is a ghost in our genetic attic – the reactivation of a 600-million-year-old program from the very dawn of multicellular life. Back then, life wasn’t a sophisticated orchestra of specialized tissues. It was more like a loose, tumour-like colony of cells, all focused on one thing: relentless proliferation. The genes for that ruthless growth are still buried deep within our DNA, like dormant code from a prehistoric operating system.

Eucalyptus sprouts on burnt tree

Davies’ atavistic model proposes that cancer is what happens when this ancient code reboots. It’s a rising from the dead. I’ve seen this kind of impossible revival with my own eyes in the eucalypt forests of Australia. After the 2020 bushfires left a landscape of charred, skeletal trees, vibrant green sprouts erupted directly from the blackened trunks – life reasserting its most primal, stubborn will to exist.

If this is true, then our strategy is all wrong. Instead of just poisoning the runaway cells, perhaps we should be targeting the conditions that awaken these ancient genes in the first place.

The clues to an ancient crime

Once you start looking for it, evidence for this “deep time” theory of cancer is everywhere.

One of the first clues is how cancer cells breathe or rather, how they don’t. Our cells generate energy using oxygen in a highly efficient process called cellular respiration. But 600 million years ago, Earth’s atmosphere was oxygen-poor. Life ran on a cruder, more primitive pathway: fermentation. Cancer cells, mysteriously, often abandon efficient respiration and revert to this ancient fermentation pathway, even when oxygen is available. This is the famous “Warburg effect.” It’s as if they’re trying to recreate the prehistoric conditions they were born in. This has led to an obvious, if difficult, treatment idea: flood the tumour with oxygen and force it back into the modern world.

But the plot thickens around the cells’ powerhouses: the mitochondria.

For years, we thought the switch to fermentation was because the mitochondria in cancer cells were broken. But that’s too simple. We now know that many tumours need healthy, functioning mitochondria to grow. Some of the most aggressive, drug-resistant cancer stem cells are completely dependent on normal respiration. Mitochondria, it seems, are not just victims in this story; they are conflicted, and perhaps central, players.

The mystery deepens in diseases like colorectal cancer. Here, we find a “broken bridge.” The carrier that escorts the main fuel (pyruvate) into the mitochondria is missing. The primary fuel line is cut. But the cell doesn’t die. The mitochondria simply switch to a backup generator, running on fatty acids instead. It’s a deliberate, strategic rewiring. This break, some researchers believe, might be the critical event that kicks off the cancer cascade.

Normal (blue) and cancer (red) cell energy generation

Then there’s the truly weird clue: cancer’s uncanny resemblance to sex. Bizarrely, cancer cells often switch on genes that should only ever be active in the testis, genes related to the formation of sperm and eggs. It’s as if these renegade somatic cells are trying to become immortal germline cells, blurring the fundamental line between the body and the seed of the next generation.

And perhaps most critically, cancer sabotages the brakes. In a healthy cell, theres a crucial “Go/No-Go” checkpoint (the G1/S checkpoint) before it divides. The cell takes stock, checks for nutrients, and ensures everything is in order. In many cancers, this checkpoint is disabled. The cell is locked in a permanent “Go” mode. And what controls this master switch? In many organisms, it’s the mitochondria, which form a giant, super-charged network precisely at this moment of decision. What are the mitochondria doing during this stage in a cancer cell? That’s a billion-dollar question.

Following the trail to the source

All these clues – the ancient metabolism, the broken bridges, the echoes of sex, the sabotaged brakes – point toward the mitochondria. Could the root cause of cancer lie not in the cell’s main genetic library (the nucleus), but in the tiny, separate instruction manual inside its power plants the mitochondrial DNA (mtDNA)?

The evidence is mounting. Cancer cells often have fewer copies of mtDNA. We find fragments of mtDNA that have escaped and embedded themselves in the nuclear DNA, potentially triggering chaos. And the mtDNA in tumors is often riddled with mutations. Some blame cancer on “bad luck” random mutations in nuclear DNA from a lifetime of cell divisions. But I believe the root cause lies a level deeper.

It comes down to a process I’ve studied for years: mitochondrial quality control. Healthy mitochondria are constantly fusing and dividing, a dynamic dance that allows them to weed out and destroy damaged segments carrying mutations. This self-cleaning process is called mitophagy.

Does mitophagy have a bearing on cancer? You bet it does. There is indeed a connection.

But that’s a story for next time.

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