Closing the loop with extrachromosomal DNA, cancer and Ptolemy

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From time to time, a story seems to write itself. This is what happened when I was working on my report on the vicious circles of DNA for the last publish of Stanford Medicine magazine. My fellow writers will appreciate when I say that scientists, Paul Mischeldoctor and howard chang, MD, PhD, were quote machines. Their enthusiasm and mutual respect – born of a chance meeting at a Stanford seminar – were palpable from our first conversations. They made my job (relatively) easy.

The article, titled “Vicious circles“, describes how tiny circles of DNA – previously thought of as mere roly-poly detritus – cooperate to dramatically increase the production of cancer-associated proteins and worsen the prognosis of the disease.

They do this by clumping together in rafts in the nucleus, allowing the stimulation of promiscuous gene expression across multiple circles. This is very different from how genes are expressed on the stately chromosomes near which circles frolic. It’s a fascinating discovery that upends some once untouchable truths in the field of genetics.

It also gave me ample opportunity to launch a seemingly endless number of circle-centric puns and analogies. (As my editors can attest, I dove into the concept that it’s better to ask for forgiveness than permission.)

But there was one fact that I couldn’t fully integrate into the story. During our conversation, Mischel made an elegant comparison: our ancient understanding of genetics as a field in which the most important players live primarily on chromosomes is akin to that of the ancient astronomer and mathematician Ptolemy. Earth centered map of the universe. It’s not exact, but enough detail was accurate that the map lasted until the 16th century, when Copernicus correctly proposed that the planets revolve around the Sun instead.

“People are visual learners,” Mischel says in the article. “But the molecular world is too small for us to see. So we create maps to help us understand. In cancer genetics, the map has centered on the role of chromosomes. But our new discoveries have turned that map upside down. Now we are redrawing our map and redrawing our journey to help patients with the most aggressive forms of cancer.”

Space constraints prevented me from including Ptolemy’s faux pas in my article. But I would like to have. Because, after all, what is an orbit if not a kind of crushed circle? Opportunity lost!

So if you want to know how SpaghettiOs, Ring around the Rosie, and bubbles in a tub relate to the next generation of cancer care, check it out. I’ll just be here twiddling my thumbs. In circles.

picture by Timothee Archibald

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