The Human Genre Project

The Gatekeepers

First there was one…. like a single disobedient child among many disciplined children.

This little one had a mind of his own: he did not heed the voice of order. The others began to shun the little one: he was different and they would not have anything to do with him. At first, the little one was content to be alone. Then his innocent mischief turned deeper and darker. He broke off from the others. Disturbed and distraught, heedless of the persistent call to conform and to obey — he sought freedom.

The old voices became fainter and fainter. Newer voices were heard, beckoning to him through the abyss: tempting voices, persuasive voices, promising great things and rich rewards. He trusted those false voices, as did his children and his grandchildren that followed. They became stronger and greater in number. There was talk of a great journey to be undertaken. Preparations were made in earnest.

But then they came: the dark ones, the demons, murdering and destroying all in their path. The demons were small in stature but great in number. The demon army took no prisoners. Merciless it was; ruthlessly it fought. There seemed to be no hope of salvation. The once great empire lay in ruins, a shadow of its former self.

The miracle the defenders had been praying for suddenly materialized. Some of those who lay near death began to recover and fight off the deadly marauders. The hordes, who would enter in stealth, were now being fought off at the portals by the gatekeepers. The silent sentinels battling the onslaught of the demon army had finally awoken from their deep slumber! Tirelessly they held the fortress against the invaders, quelling the black tide and restoring the vestiges of the once great empire. The empire would survive and rebuild. They would restore the great splendor of their forefathers. Their influence would spread far and wide, and this time they would show no mercy.

The gatekeepers had finally awoken ...

Author’s note: In this story the ‘disobedient child’ is obviously a cancer-initiating cell which gives rise to the tumor. The ‘demon army’ is the chemotherapeutic drug that is being used to kill the cancerous cells. The enigmatic ‘gatekeepers’ are molecules of P-glycoprotein (chr 7q21.12) pumping out the anti-cancer drug and allowing the tumor to become drug resistant and thus re-establishing the ‘empire’.

I have always found it ironic that a molecule (P-glycoprotein) which actually evolved to protect cells against toxic insult (hence the name ‘gatekeeper’) could be subverted by tumor cells for their own intents and purposes (i.e. survival). I only hope that the ultimate fate of the human race does not lie mirrored in this irony.

Dr. Karobi Moitra
Laboratory of Experimental Immunology
Human Genetics Section
Cancer Inflammation Program
National Cancer Institute at Frederick

Karobi Moitra