A nightmare that starts with one rogue cell

WE START where it always begins — with a single cell. The scene? It could be anywhere in the body, but in my late partner Zarah Harrison it was the interior lining of her bladder.

Imagine if we could zoom in. Nestled alongside millions of identical neighbours in this delicate layer is a cell: a tiny, unremarkable, disc-shaped bubble of gelatinous life just micrometres in diameter.

From the outside, all is quiet, the silence belying a hum of invisible activity as the cell’s energy is devoted, as it has been for the past few weeks, to replicating what would be — if stretched out — nearly two metres of DNA, the cell’s blueprint, packed into the nucleus at its centre, with near-perfect fidelity, checking, double-checking, preparing, recharging.

Suddenly, inside the cell, things spring into life as it starts once more to divide, each step tightly co-ordinated and refined by evolution over billions of years. The delicate membrane surrounding its nucleus dissolves, while simultaneously the DNA contained within begins slowly to condense into 46 chromosomes, each subdivided into genes, containing two duplicates of a vital chunk of genetic information — thousands of genes held in a few nanometres; the book of life, in duplicate.

From nowhere, a rigid scaffold emerges, stretching out across the cell’s interior, forming a series of ghostly, skeletal tracks that run from one end of the cell to the other. This causes the disc-shaped cell to swell into a sphere.

Then, like a regiment of soldiers lining up in formation, all 46 condensed DNA chromosomes start to assemble across the cell’s diameter, perpendicular to the skeleton, each somehow knowing its precise place in the proceedings.

So far, so good — and with everything in place, the real action begins. The skeleton expands, forcing the cell apart, tugging one half of each chromosome pair in an opposite direction.

The balloon inflates further and yet more newly formed scaffolding (this time radiating out from the centre to the cell’s outer membrane) pulls inward, constricting the membrane around the balloon’s centre as if it were being cut in half by a belt strapped around its middle. Slowly at first, then increasingly rapidly, the membrane draws in further while the chromosomes segregate into two matching groups that are safely separated, one in each ‘half’ of the balloon.

Then the belt tightens to pinch the cell clean in two. The mother cell has a new daughter. But something is amiss. Somehow, at some point during the replication and the wrenching violence of the cell division, a defect has become embedded in its DNA that will sow the seeds of a future tragedy.

Years pass. Deep in the lining of the bladder, the mother cell has been robotically carrying out its duty, division after division, daughter after daughter, its lifetime progeny now numbering millions.

And all this time, despite appearing outwardly normal, this particular mother cell and all its progeny have carried that tiny defect in their DNA, in the process losing the instructions to assemble a particular protein that governs whether the cell that contains it should divide or not (if it’s faulty).

Luckily, the chromosome carries a back-up to this control gene, on its identical twin. But today, again by awful coincidence, something inexplicably jams, twisting and breaking the DNA strands as the cell replication process begins again. Immediately, the replication machine seizes up and the working copy of the gene on that twin chromosome is destroyed.

Molecular alarms ring out. Sensing the error, the cell finds the chromosome’s faulty sibling and uses it as a template to try to patch up the fractured DNA.

In doing so, it embeds the defect for ever into the cell’s genome. A vital cog in the cell’s control system has just been irretrievably overwritten in error. From now on, whenever the mother cell uses this garbled template, each of her daughters will bear this deranged, faulty cellular software, and

each is now free to grow and divide unchecked. Nature’s brake cable has been decisively cut. And each cell exponentially becomes two, becomes four, becomes eight, becomes 16 . . . and gradually, in Zarah’s case, from this small patch of the bladder’s lining emerges an ever-expanding clump of millions of proliferating, impatient, unruly cells — mere millimetres in diameter but massive in consequences.

As each of these rogue cells gears up for a new round of division, yet more catastrophic genetic events occur as they try to replicate their jumbled, muddled chromosomes in slapdash, make-do fashion. Frequently, these catastrophes are just too much for the resulting progeny to bear: the cells self-destruct, shedding debris far and wide. Yet others survive to accumulate new errors — and new powers.

Sensing something amiss, nearby immune cells mobilise to try to contain the damage, amassing at the edges of the anomaly.

Gently, carefully, the immune cells extend their tiny molecular sensors, stroking the surface of each rogue cell, looking for outward signs of aberration. Alas, despite their odd behaviour, their scrambled DNA and their impatient, rapid growth, as far as the immune system is concerned, each of the rogue cells still ‘feels’ just like every other cell in the bladder.

Nothing to see here. Move along. And so, ignored by the immune system, the mass continues to grow unhindered, now just a few steps away from transforming into cancer.