Q&A: A Tale of Two Viruses: Parallels in the Research Trajectories of Tumor and Bacterial Viruses--A Virtual Discussion with Neeraja Sankaran

Select answers from Neeraja Sankaran, author of A Tale of Two Viruses: Parallels in the Research Trajectories of Tumor and Bacterial Viruses

Q: I wonder if you could talk a little more about why this particular animal-based sarcoma so captured the attention of these important scientists? Historically, why do some diseases get scientific study when others might not?

A: Opportunity is the first reason that occurs to me. So, to begin with it was a new problem—a farmer brought in a bird with a tumor and so it was what Peyton Rous investigated. After all, he had been hired at the Rockefeller specifically to do cancer research—at a place that was explicitly not an institute of cancer research. So there was little or nothing established there already—he didn’t get to walk into a lab and help tackle an on-going problem, as James Murphy who arrived a year or so later did. In 1910 Rous was new at the Rockefeller and I’m not sure that at the time he had even begun working any particular problem. So when the right opportunity came along—so opportunely (if you’ll pardon the overuse of the word)—he took it on.

Ease of the model also plays a part—one cannot investigate the transmissibility of human tumor to another human. So unless there is a suitable animal model for a disease one could not carry out certain avenues of investigation.

The fact that the sarcoma was transmissible not only by transplanting bits of cancerous tissue (not unusual) but by injecting cell-free filtrates of ground up tissue, made it unique and therefore not only interesting but also allowed him to stake out his own territory. The research actually stalled,  dried up quite early, in the face of discouraging data, negative results and leads, but since it was possible to maintain the tumor tissue—at I suspect relative low cost in terms of both funds and space—he decided to do so and supply it to others interested in further investigating the problem.

Turning for a moment to the “other” virus in this book, the bacteriophage, its 1917 discovery by Felix d’Herelle took place under very different circumstances. Here it was an offshoot/byproduct of an investigation into a very specific problem for very specific reasons. d’Herelle had been assigned the microbiological investigation of a particularly nasty outbreak of dysentery at a garrison stationed just outside Paris. Dysentery was a known disease with an established microbial cause by then (actually two since people had already distinguished between bacterial and parasitic, i.e. amoebic types, but the unusually severe symptoms of this outbreak had led the chief medical officer Bertillon to suspect that the bacterial strain was different. In d’Herelle’s words, “one did not need to be a great hygienist to find the cause…” But having pinpointed the cause fairly early, he continued to follow the cases of convalescing patients and an unusual finding during routine examinations of stools etc. led to his discovery.

To answer the second part of your question—why some diseases get attention and other do not—both extremes, i.e. continued negative results or very quick resolution of a problem might have the same effect, in a problem not being pursued. Continued negative results and dead ends might render a problem “unsolvable” until newer techniques are developed and give one idea for instance. The early trajectory of bird sarcomas is a good case in point. Rous himself stopped work on the problem as early 1915 less than 4 years after his initial discovery, quoting precisely the discouragement of negative results as his reason. And the field lay fallow for nearly a decade until new results from across the pond, revived interest all over the world. As for the negative impact of positive results—especially in the context of a hospital laboratory, where a laboratory investigation is undertaken for a specific goal, once that goal is achieved, then the case is closed and the investigator moves on. Or as it happened in the case of the bacteriophage, a new tangential discovery completely overshadows the initial investigation.

Q: The examples of correspondence you show are really interesting. What do they reveal about the scientific research process in the 20th century. How similar or different is the process today in an age of digital communication and data sharing?

A: I think one thing —the most exciting thing really—about using correspondence (epistolary sources) to reconstruct history is the immersion into the lives and times of the people writing the letters. And to me it was amazing how much some things change/have changed while others surprisingly feel as contemporary as if written yesterday! I studied microbiology before I ever became a historian and some of the things the scientists talked about were very familiar and it was actually quite remarkable to thing that ways of culturing bacteria growing them in the lab and identifying colonies had not changed in decades! But other references are completely obscure because they cite obsolete techniques etc.

One thing about research then vs. now that is striking is the pace—letters took much longer of course, (there’s a reason its been dubbed snail mail in this digital age)—and often materials took even longer. Also easier nowadays to send the same message to multiple people at once. Back when cc literally meant carbon copying, i.e. placing a sheet of carbon paper under the paper to receive an imprint of the original letter—that was much more difficult or impractical. But still these were mechanics. To give an entirely unsatisfactory answer to this question “the more things change the more they stay the same.” or equally unhelpfully—some things have changed drastically others remained the same. Exactly what the some and other are, however, varies in each case.

Q: Can you talk more about Rous s'working methods? How did they figure out the chicken virus?

A: I don’t think that Rous’s working methods were in and of themselves particularly unique. He proceeded rather systematically to examine the tumor at different levels: gross, microscopic, chemical and try to induce it in a new animal to try and pinpoint the cause. The Koch’s postulates scheme of searching for the cause of a disease was in place even if the disease was not infectious. The early papers (1910-12) go into the details of the initial plan of attack, so to speak.

It took a long time to figure the chicken virus—nearly a century if you think about the actual mechanism and some parts are being figured out even now, I’d venture to say.

Q: Is our understanding of what viruses are still evolving?

A: Oh absolutely! In the light of what they can do, new discoveries etc. Furthermore, they themselves are evolving. But our understanding of some of the basic characteristics, that set them apart from other categories of beings for instance, have not really changed since the 1950s.

Q: When did scientists start to see viruses? Was seeing viruses under a microscope, key to proving viruses caused some tumors?

A: May I refer you to chapter 6 of my book? Jokes aside, though, it sort of depends on the specific type of seeing. The crystallization of virus particles in the 1930s allowed us to “see” viruses—or rather, the configuration of their constituent molecules—in a certain way; the cultivation in different types of media—e.g. leaves of plants, bacterial cultures (both in liquid and on solid media), chick embryos and ultimately on cell cultures—offered a different set of pictures of viruses. These images are of the lesions they cause in their hosts. So while you could not actually see the viruses themselves, you could see them through their effects. Without a doubt though, it was the invention of the electron microscope (1937) that brought the viruses into the visual realm.

To the second part, I’d have to say, that this sort of seeing was not key... not really. What it did was to help clinch the evidence. But the similarity of viruses to other like-sized things in cells, etc., sometimes confounded matters instead of clarifying them. Even more than photographs (photoshop manipulators take note!) electron micrographs are open to both manipulation and, even more so to differing interpretations of what one was seeing.

Q: The APS sounds like a very rich archive! Do you have plans for future projects using these collections?

A: Would love to!