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No one here but us chickens

A cancer eureka moment

Jennifer Rohn 4 January 2019

But deep down, Peyton the pragmatist, Peyton the truth-seeker, desperately wants this particular hypothesis to be true

Editor's note: We are pleased to present the twelveth installment in our series, The League of Imaginary Cats. Read more about the Series in our accompanying editorial, and use the navigation links at the top right to catch up.

It’s early. He’s the first one in: just the way he likes it. Unlocking the lab doors, he’s not sure which he senses first: the rustling of the hens, or the powerful ammonia stench of their excrement.

Rows of cages, dozens deep. The bars glint in the light. Behind them, the birds start fussing as he steps into the room. Round amber eyes framed by pink flesh, unblinking and almost reptilian. Soft feathers in grey and cream stripes, laid down in perfectly predictable patterns, the same in hen after hen, in some predetermined miracle of life that no scientist yet understood.

“You stink,” Peyton says, not unkindly, to the hen in the nearest cage. “No offense, darling.”

The hen remains silent. He chuckles, remembering what his friend Oswald Avery said last week: “You’ve been working too long with only fowls for company – one of these days they might start talking back!”

Peyton goes to the window, telling himself that he’s doing this first because the lab needs to be aired out. But he knows that’s not accurate: what he’s actually doing is delaying the moment of truth. Never mind that he leapt out of bed, the dream so vivid that it took him a moment or two, panting in pre-dawn darkness, to realize that it wasn’t actually real. Never mind that he threw on clothes with no regard for style and coordination, forewent breakfast, and dashed towards the Institute with the sun only just rising behind him.

Could the dream have been a sign that today was the day?

He snorts. Peyton Rous, M.D., acting like a foolish boy. Or like one of those dusty, black-eyed women who used to skulk behind the traveling circus tents back in Texas, cajoling coins in exchange for a reading of the palm or coyly upturned Tarot cards.

Peyton tosses his coat onto a nearby lab stool and hauls up the old window sash. Sweet May air pours into the lab. Below him, the Upper East Side is finally starting to stir, to catch up with Peyton’s enthusiasm: the clatter of horses’ hooves on the roads, the shouting of tradesmen, the laughter of children and the scolding of mothers.

This wasn’t Texas, and Peyton wasn’t a boy. He was a grown man, with a medical degree, recently put in charge of the Rockefeller Institute’s laboratory for cancer research. Fancy taking a dream seriously! If he told Oswald about it, he’d never hear the end of it.

But he couldn’t get it out of his mind. In the dream, he’d seen the tumor, blooming from the hen like a flat bud. When he touched the growth, the bud had opened to reveal a blood-red flower, quivering with life and vitality. Peyton had leaned closer, somehow convinced that the flower was about to reveal the secret of cancer, once and for all – that he alone had been chosen for this revelation. But just as the voice began to speak, he’d woken up.

It had been a year, more or less, since he’d made the first breakthrough with the hens. He’d taken a tiny bit of tumor from one bird and transplanted it into a healthy bird – and about a month later, the second bird had developed the same growth: a nasty-looking sarcoma, glistening yellow and pink when he cut into it. A transmissible tumor, a tumor indistinguishable from those that humans developed! No one thought that human cancers were contagious like that – was this just an anomaly? Would it have any application for understanding the disease in man? And how on earth could the cancer cells spread like that? What made these hen tumors special?

Peyton had a bet with Oswald that there was something microscopic associated with the tumor that was causing it – a minute parasitic organism, say. They’d been having a drink, talking over their latest research, when the idea came to Peyton: the feeling that there was something more going on than just cancer cells surviving as a graft. There was a lot happening in the medical field to do with ultramicroscopic organisms making people ill – new germs were being discovered all the time. Peyton himself had first-hand experience with the perils of the microscopic: in medical school, he’d scraped his finger on a diseased bone during a routine autopsy and had contracted tuberculosis. The invisible world was teeming with transmissible perils – perhaps cancer was harboring a similar secret life.

But Oswald, who was obsessed with bacteria and ran a big lab devoted to their study over in Brooklyn, thought the idea of a tumor being caused by one of his darlings was patently nonsense.

So Peyton had gone back to his hen tumors and done lots of tests, but could find no evidence for any bacteria (much to Oswald's delight). Maybe it was something smaller?

Peyton looks out over the New York suburbs, where sunlight is reflecting off the windows on the row of buildings opposite. He smells the aroma of fresh bread rising from the nearby bakery, reminding him of his empty stomach. A whiff, too, of lilac, and the plaintive cry of doves from the gardens of the Institute. The air is dewy and still cool, but the sky shimmers with a clarity that promises later warmth. Peyton is not sorry to see the end of this overlong New York winter.

Were his hen tumors caused by a germ? There had been only one way to find out. He had spent many hours in the lab over the dragging winter months, working out how to extract these putative invisible germs. He’d ground tumors lovingly in sterile sand, shaken the mush in buffers, spun it down in a centrifuge to separate out the solid bits of tissue and carefully drawn off the clear liquid on the top. More centrifuging, more drawing off until the tumor extract was absolutely clear. Not satisfied, he passed the fluid through a filter with pores so tiny that no bacteria could possibly get through. And then this stuff, pale yellow, free of any cancer cells or known forms of microscopic life – but brimming with possibility – had been injected into the breasts of a few healthy hens.

And then the vigil had begun. Every morning he checked the breasts of his hens. At first, of course, it was mere formality. Cancers take time to form. Days. Almost certainly weeks. But of course, this was something entirely new: who could be sure of the timing? So every morning, the ritual inspection, the meticulous jotting in the notebook of date, time, appearance around the old jab wound. As the weeks went by, these mornings began to take on a feeling of quiet desperation for Peyton. Even Oswald stopped teasing him – “Any signs of unsightly bulges in your lady friends?” – sensing that the stakes were actually higher for Peyton than he’d been letting on, higher than just a silly bet on a bottle of decent single malt.

Peyton was disconcerted by Oswald’s earnest sympathy, which was completely out of character.

“The truth is the truth,” Peyton told his friend. “You may like proving what you already believe, but I just want to find out how it is, one way or the other.”

But deep down, Peyton the pragmatist, Peyton the truth-seeker, desperately wants this particular hypothesis to be true. His colleagues had not, if he is honest with himself, been very impressed with the initial bird–tumor transmission. The story needed more oomph – more magic. A special angle that would really grab their attention.

Something about the dream has renewed his hope – which is actually the last thing he wants. For he had started preparing himself for failure, for disappointment, several days ago. The injected birds remained stubbornly disease-free: in fact, they seemed almost perversely healthy, hale, strutting about their cages with a cheerfulness that made Peyton grit his teeth.

But now, suddenly, leaning against the window and breathing in the soft air, he is almost light-headed with expectation. He is, truth be told, afraid to look. Afraid to find out that the dream was just that, a silly fantasy concocted by the illogical parts of his brain. A fantasy trying to make a mockery of the objectivity for which he is already notorious. If only his Rockefeller colleagues could see inside him now.

He turns away from the window at last, approaches the cage. His heart rate has accelerated, blood singing in his ears. As he reaches for the latch of the cage, he notes clinically that his hands are shaking.

“There won’t be anything,” he whispers. And then that maddening counter-voice he can never quite squelch: But maybe there will!

Though his heart is conflicted, his hands know what to do. The chicken is just a number in his notebook, but to her face he calls her Helen, after the first girl he ever kissed. Her feathers are warm and soft, and she is unconcerned by this fumbling after so many intimate mornings together. He pushes away the vestigial flight feathers to expose the site of the inoculation.

At first, he thinks it might be a trick of the light. Turning the bird this way and that, he sees, with an unstoppable surge of triumph, that there is a swelling centered over the old wound. He places fingertips to the raised area and feels a definite mass – it is unmistakably a tumor. A tumor, transmitted by a liquid that, thanks to his meticulous preparation with the centrifuge and the filters, contains no cells, no bacteria, no entity that science recognizes as an agent capable of causing cancer on its own.

When he writes up the paper later, he is careful to produce the diffident skepticism that is expected of men in his profession: one cannot rule out at this time some chemical stimulant produced by the initial cancer. Work is being directed to its experimental verification. For the moment we have not adopted either hypothesis.

But in his heart, he knows it’s a microorganism – perhaps akin to one of these so-called viruses recently described that produce nodules in tobacco leaves, or foot-and-mouth disease in cattle. Something small and deadly. Something mysterious and beautiful. Something that just might, if he’s very lucky, be the key that unlocks the most feared of all human diseases.

He puts the bird back into its cage, and moves on to the next.

The Discovery of Retroviruses

And sure enough, years later, generations of researchers will embrace Peyton’s germ. They will call it Rous Sarcoma Virus, and will use it to bring the study of cancer into the modern molecular era. He will be awarded the Nobel Prize for this, but he has to wait a staggering 55 years for the honor, and he dies only a few years later.

I wish I could have told him all about it, on that long ago May morning in 1910. How his invisible agent was actually a retrovirus, related to HIV – a virus that, in my day, has wiped nearly 40 million people from the map. I would tell him how Rous Sarcoma Virus causes tumours because it has stolen a chicken gene – snatched it right out of the genome like a microscopic shoplifter. A gene that causes cells to go rogue and divide out of control. I long to tell him how viruses related to Rous Sarcoma Virus will be discovered in mice, rats, cats, and a host of other animals, and each will be found to steal different genes from the hosts they infect – genes that humans also share. So-called proto-oncogenes that, when subverted, make cells grow, divide, fail to commit suicide when faulty, fail to respond to the body’s normal checks and balances – to bloom like deadly flowers in the garden of the body. And although most human cancers will turn out to be spontaneous and non-transmissible, there will be a few drastic exceptions, such as human papillomavirus, which causes cervical cancer in women.

What must it have felt like to study something so intricate, yet not know what DNA even looked like, or what a gene really was? How would it have been to work in a lab when studying biology was like lighting a match in a stadium full of darkness? I would love to explain to him that as each virus’s illicit cargo was studied, another light went on and a new piece of the puzzle of human cancer was put into place. I wish I could tell him that when I was first starting out in research, I investigated a close cousin of his virus in cats which had shoplifted a gene never stolen before, and that his example inspired me to rule out nothing, no matter how crazy.

A slightly different version of the fictional part of this piece was originally broadcast on BBC Radio 3 by the author.