How many genes in our genome?

black knight

The metaphysics of genomics

“None shall pass,” declaimed the Black Knight when confronting King Arthur (and Patsy with his coconuts) in Monty Python’s ‘The Holy Grail’. Facing Arthur- King of the Britons- in single combat, the Black Knight was careful to sidestep the debate over whether “none” is singular or plural. His statement, “None shall pass” is safely ambiguous in this regard. However if he had been able to defeat Arthur (he didn’t), back at the castle that night would he have clarified his “none” with the singular, “No one was able to pass me!”, or the plural, “Not any were able to pass me.”? Being completely dismasted in the battle, it’s a moot point for him, but the question still stands.

Back in the early heady days of the genome project, a similar question that often got booted about was, “How many genes are there in our genome?” No lopping off of limbs was involved, but much argument was had, and heavy betting was on a number around twenty-five to thirty thousand, though some factions advocated for a much higher number, nearer to one hundred thousand. I was in the camp of the latter group. The resolution of the disagreement depended on agreeing upon what, exactly, is a gene, for which there can be many possible definitions, and whether “gene” is singular or plural. The 30K faction’s “gene” was not the same as the 100+K faction’s “gene”. Reporters learned to ask other, easier, questions, or just to leave geneticist alone entirely.

This isn’t just a problem in genetics, but a basic one of philosophy. That is, “How do we know what anything is?” This dog may look different than that dog, but we can agree this dog is a dog. Why, or how?

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Lord Byron, defender of textile workers and primary care physicians

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Or why not to bring your entire genome sequence print-out to a doctor visit

Before there was Justin Bieber, or for those of us in Asia, any one the boys of a K-pop band, there was Lord Byron. To many of the women of the early 1800’s, as well as more than a few men, he was the epitome of romance. His noble birth, alluring poetry, spendthrift ways, his many loves, his foreign travels and adventures, all created- abetted by his active promotion- an image of exotic allure that captured the time. Even now if one’s love presents herself in a black dress, many points will be scored by repeating the opening lines to one of his most remembered poems,

She walks in beauty, like the night
Of cloudless climes and starry skies…

His reach extends even into today’s world of genomics, albeit tangentially and if one is willing to stretch a point. I count three connections:

The first of these links occurred during a rainy visit to the vacation home of the English Romantic poet Percy Shelley in Switzerland, where he and the Shelley’s competed in storytelling. It was on these inclement days, cooped up with Byron and friends, that Mary Shelley began the iconic novel, Frankenstein. We often call upon her novel today when comparing our modern use of genetics for recrafting life to Dr. Frankenstein’s efforts (though his were more needle, thread and lightening based), and in deriving the term ‘Frankenfood’ to describe genetically modified food.

Secondly, Byron’s only legitimate daughter, Ada Lovelace (née Bryon), wrote the first extant computer program. This program was meant to run on Charles Babbage’s mechanical computer, the “analytical engine”. Unfortunately Charles’ analytical engine was never built, and Ada’s program has yet to be run. Nonetheless she gets the credit for being the first computer programmer, and one of the key differences between genomics and its forerunner, genetics, is the necessity of computational power. Genetics deals with just a few genes at a time, genomics deals with all of them. Though I wouldn’t want to have to do genetic linkage analysis on Babbage’s contraption, our modern computers can trace a direct lineage back to his device, and to Ada Lovelace’s program.

And finally, Lord Byron defended the Luddites. This was a textile worker’s movement at the rise of the 19th century who claimed to follow in the footsteps of a Ned Ludd, and who smashed the new powered looms and mills that threatened their livelihoods. At that time, as well as now, to say that someone was a “Luddite” was a pejorative, impugning them with an unthinking rejection of technology and progress. However Byron championed them, and his debut speech before the House of Lords was to denounce a new act which would allow the death penalty for those who damaged a machine. His defense of the Luddites was that their frustration at being abandoned in the face of technological advances was worthy more of compassion than of capital punishment. He also wrote “Song For The Luddites “, which included the verse:

When the web that we weave is complete,
And the shuttle exchanged for the sword,
We will fling the winding sheet
O’er the despot at our feet,
And dye it deep in the gore he has poured.

Pretty strong stuff, though he told a friend that, “I have written it principally to shock your neighbor, who is all clergy and loyalty.” People like Byron tend to think of themselves as too clever by half.

Akin to Byron’s defense of the textile workers, let’s not dismiss an Annals of Internal Medicine editorial as being written by mere Luddites.

It is this defense for the Luddites that lets us connect Byron with genomics: inspired by Byron, I’m not going to dismiss an editorial in this week’s Annals of Internal Medicine as being written by mere Luddites.

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