The Story of Peyton Rous and Chicken Cancer

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“Tumors destroy man in a unique and appalling way, as flesh of his own flesh which has somehow been rendered proliferative, rampant, predatory and ungovernable.”

So began Peyton Rous’s 1966 Nobel Lecture, the year he won the prize in Medicine, just four years before he died, and 56 years after a woman brought him the chicken that would set his scientific career in motion.

Rous was working at the Rockefeller Institute (before the name was changed to Rockefeller University) when a woman, her hands slightly arthritic, came in carrying a Plymouth Barred Rock hen. Of course this was no ordinary fowl: a large tumor was sticking out of its belly, making the hen look as if it had swallowed its own egg. And it was a turning point for cancer research.

It turned out that this tumor became the first scientifically documented transmissible avian sarcoma. As Rous wrote in his 1910 report on the chicken’s tumor:

“In this paper is reported the first avian tumor that has proved transplantable to other individuals. It is a spindle-celled sarcoma of a hen, which has thus far been propogated to the fourth generation…”

On first glance, it’s hard to see the significance of what Rous wrote about this little hen. But the discovery that this sarcoma was transmissible set in motion an entirely new way to study cancer; that is, through viruses. Although about 20% of human cancers are now thought to be transmissible through viruses, for the most part virus-caused cancers are confined to other animals. Chickens, cats, and mice appear particularly susceptible, although our awareness of virus-related cancer in these animals might be mainly due to the fact that these are the ones people come across through agriculture, pets, and laboratory research.

However, the understanding that viruses can somehow carry cancer from one animal to another provided science a model with which to unravel how the transformation from normal to cancerous happens.

It is true that the idea that cancer could be transmissible was already circulating. In the 1840s, an Italian scientist named Domenico Rigoni-Stern had made the observation that nuns in Verona rarely developed cervical cancer, whereas the disease was far more common among married women in the same region. The virus responsible for the difference wasn’t identified until 1983, but it was obvious that transmission had to be part of the cause. Lung carcinoma in sheep was also known to be transmissible in the 1800s.

The very first leukemia-causing virus in chickens was found in 1908. However, the destructive nature of leukemia was not widely recognized at that time, and the discovery of this virus barely caused a stir.

And neither did Rous’s, really, at least for a while. He continued to study this avian sarcoma virus for a while, and found that the tumor, just a few months later, had greatly increased its transmissibility. A few years later, Rous reported two other chicken tumors that were also transmissible, which indicated that the Plymouth Barred Rock hen’s tumor was not an isolated, one-off incident.

But then World War I came, and Rous turned his attention to blood and its need for it among injured soldiers. He helped establish the first blood banks in the United States. Later, he turned his attention again to oncogenic viruses, and was one of the first people (or maybe the first) to think about cancer in terms of two stages: initiation and the progression.

The implication of what became known as the Rous sarcoma virus (RSV) would not be recognized for decades. It wasn’t until the 1950s that studies of RSV and other retroviruses would come into their next incarnation, mainly due to the discovery of reverse transcriptase, the enzyme that enables RNA-based viruses to transform their genetic code into DNA, by David Baltimore and Howard Temin (who won a Nobel Prize for their work just a few years after Rous’s award was made).

That 55 years elapsed between Rous’s discovery and his Nobel recognition is, in part, a testament to the way time operates when it comes to science. There’s no way to know what is going to turn out to be important and why.

Interestingly, Rous’s lecture during his acceptance of the Prize included an adamant denial of the link between cancer and oncogenes (that is, normal human genes that are transformed into cancer-triggering genes for various reasons). Yet it was his discovery of RSV that eventually made that link possible: Bishop and Varmus’s landmark work proving that the oncogenic portion of viral DNA had actually been picked up from human DNA is one of the most significant moments in cancer research. That discovery bore a direct connection to Rous’s discovery six decades earlier. (Bishop and Varmus won a Nobel for this work in 1989, so a trio of Nobels in this story.)

Peyton Rous was born in 1879 in Texas, his father having bought land there in the 1860s, out of fear of the destruction the Civil War was going to bring. His family eventually moved to Baltimore, where Rous’s mother was left to raise three young children after his father died. His mother stubbornly refused to return to Texas, where extended family could have helped her handle the challenges of raising this brood on her own, because she wanted her children to have a good education, which was more readily available in Baltimore at the time. It was the wild flowers in the field around his home that would first evoke the naturalist in Rous, and that would lead to his first “scientific reports,” a list of all the flowers he’d identified in the area, which he submitted to the Baltimore Sun at age 18. (The newspaper printed the article and, yes, paid him for it.) A lifelong scientist driven by his curiosity and humanity, Rous may have received the coveted Nobel in his twilight years, but one has to believe that the timing was of little consequence to him. As he himself said during his banquet speech,

“Tonight I am supposed to speak to you as the oldest of our Nobel group. But William James, a greatly loved American philosopher of long ago, once said: “Many of the old are young to life” – and that is my state this evening. I greet you as a fellow student.”

For more on this amazing story, read this wonderful review, “100 years of Rous sarcoma virus,” by Robin A. Weiss and Peter K. Vogt.

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Photos:
Camilla, the Plymouth Barred Rock Hen, by SillyDog, from Flickr, Creative Commons License
(Francis) Peyton Rous, from NNDB

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