In the late 1960s, NCI received the modern-day equivalent of billions of dollars to establish a viral oncology program.
At the time, the study of the role viruses played in cancer (or whether they played any role at all) was unknown.
This could have been either a triumph or a huge and embarrassing waste of money.
“Many people liken the virus cancer program to a Moonshot. In that case, it’s a Moonshot that was building a rocket for a planet people couldn’t agree was even out there,” said Robin Scheffler, associate professor in the Science, Technology, and Society Program at Massachusetts Institute of Technology, said to The Cancer Letter. “This is really, really big science. It’s bigger than the Human Genome Project.”
Scheffler is the author of A Contagious Cause, The American Hunt for Cancer Viruses and the Rise of Molecular Medicine, a history that traces the ways in which NCI’s wild gamble on viruses paid off.
“They eventually set up a series of programs, the Special Leukemia Virus Program, the Special Virus Cancer Program, and then just the Virus Cancer Program, which are using these managerial methods, taken from the defense department in NASA, to oversee the discovery of a human cancer virus and the development of the vaccine,” said Scheffler, a historian of the modern biological and biomedical sciences and their intersections with developments in American history,
While researching the beginnings of cancer virology for his book, Scheffler looked for the discovery that led to the influx of funding for cancer virology.
“I went back, reading the medical literature, reading the scientific literature, reading annual reports of the American Cancer Society, reading Congressional testimony, trying to find why people had agreed that this really controversial idea suddenly merited the investment of what in today’s terms would be billions of dollars in medical research,” he said. “And I couldn’t find it.”
The story of viral oncology in Scheffler’s book became not just one of science, but also of politics.
“It’s partially within the push for the war on cancer of 1971 that Mary Lasker provides, which, once again, in a year or a few years, quadruples the budget of the National Cancer Institute, and gives it unprecedented authority to oversee scientific research,” he said. “That really gives the National Cancer Institute this broad power to conduct and sponsor research on viral oncology, despite the fact there are still many critics out there.”
In the early years, the medical field wasn’t friendly to NCI’s viral oncology program, Scheffler said.
“It’s a case where there’s no agreement on the actual existence of human cancer viruses before the program is created,” he said. “The thing that I find very remarkable is that despite this level of controversy, the National Cancer Institute really does make it possible to do viral oncology, and especially to start discovering the links between RNA tumor viruses, or retroviruses, and the genetics of cancer, in a way that probably would not have happened for quite a while otherwise.”
Who were the skeptics and what did they say?
“You have major virologists, like [Macfarlane] Burnett, who are just based on their knowledge of virology, are saying, ‘We can’t, we just don’t have this yet. There’s no proof in terms of how I would demonstrate the link,’” he said. “You have many doctors, from places like Sloan Kettering, from places like Boston Children’s, who just think that the idea of a virus makes sense in reference to their clinical experience.
“They’re much more interested in the possibility that there are other causes, or they think the idea of talking about causes is a distraction from developing surgical or chemotherapeutic treatments against cancer, which they see as being the most promising way, that not thinking about what caused the virus, but really just how to treat it.”
The search for a cancer virus led to conflict as it became more entangled with molecular biology, Scheffler said.
“You run into a lot of culture clash issues between people who work in the clinic and people who work in molecular biology,” he said. “That’s just a general added question of who do you go to to understand disease? You go to the doctor who has experience with it, or are you getting into these greater and greater degrees of molecular abstraction from the disease itself?”
The history of viral oncology is not straightforward, Scheffler said.
“I was especially intrigued at these things called tumor viruses that seemed to be playing this really important role in bridging basic molecular biology with its application to human health,” he said.
The story of viruses in cancer is one that begins in antiquity, Scheffler said, back when Greek surgeons worried that “seeds” of cancer tumors could spread within the bodies of people they operated on. When germ theory emerged in the 19th century, scientists speculated whether cancer was contagious.
“If you look at early campaign and public education materials from the American Society for the Control of Cancer, which becomes the American Cancer Society, they are still at pains to say cancer is not contagious, and it’s also not hereditary,” he said.
Scheffler begins his book with a story about a young girl who survived leukemia in the 1960s, back when people worried the disease was contagious. A photographer from LIFE Magazine was assigned to take her photo for a news story.
“She insists, as a young woman, only being photographed with her back to the camera so she couldn’t be identified, because she’s so afraid of being stigmatized as a cancer carrier,” Scheffler said.
The idea of cancer as contagion led to the study of cancer virology beginning with “the codification, or the formalization of some of the ideas of germ theory, into microbiology and bacteriology,” Scheffler said.
Discoveries that Epstein Barr and hepatitis B could cause cancer and their significance in viral cancer research were made much later.
“One of the fascinating things about this story is that the endings are never quite written at the moment that people are doing the work,” Scheffler said. “It’s things that people often figure out only after several more decades of study and debate and argument.”
For Scheffler, there are two major arcs within the complicated history of viral oncology.
“The first is how we’ve come to understand the nature of cancer at an increasingly smaller, and smaller, and smaller scale,” he said. “Moving out of the clinic and into animal organisms, animal models, into cell culture, and now into, of course, the various protein molecular mechanisms we associate with understanding how cancer works.
“And understanding those mechanisms is a place for developing interventions that might be truly effective—personalized medicine, immunotherapy, things like that, and of course, a number of cancer vaccines that arise from especially the application for hominin DNA to vaccine manufacturers in the ‘80s and ‘90s.”
Cancer research has become a bigger science, Scheffler said.
“It’s no longer just one person in a laboratory, it’s whole institutions being funded by ambitious, forward-looking government programs,” he said. “Which, in turn, means that cancer research is a part of a broader conversation we have in society about—how do we deal with health and disease? What should we be prioritizing? How do we frame problems like cancer? Are they simply things that we confront in the laboratory? Are they things that we think about in terms of their social and environmental roots?
“Vaccination as a whole, is one of these biomedical interventions that really promises immense aid to human health. If you can get people vaccines quickly enough, you can really do so much good for them. The idea of having vaccines that would be preventative against cancer is wonderful.”
Scheffler spoke with Alexandria Carolan, associate editor with the Cancer History Project. A podcast recording of the conversation with Scheffler is available above.
Transcript
Robin Scheffler: There’s a number of places that it begins. When I started writing the book, I actually started in the middle of the 20th century. And I was fascinated by the relationship between cancer research and the growth of molecular biology, and I was especially intrigued that so much basic work in virology was being funded by the National Institutes of Health, and it seemed very far from human health. I was especially intrigued at these things called tumor viruses that seemed to be playing this really important role in bridging basic molecular biology with its application to human health.
I was especially confused because back then, I didn’t realize that cancer was thought of, ever, as a contagious or viral disease. So, to start A Contagious Cause, I went farther and farther back trying to find where that idea had come from. It’s an idea that really goes back to antiquity.
You have concerns expressed by Greek surgeons that so-called “seeds” of cancer tumors can be spread, both within the bodies of the people they were operating on, and possibly between people. Then really, by the 19th century with the emergence of germ theory, you see many, many discussions of the idea that cancer is contagious and could be passed from person to person.
There’s a great deal of fear and concern for so-called cancer houses in 19th century Britain and France, which are houses where people are all seeming to come down with cancer. Although there’s environmental explanations offered in terms of having bad air, people began to think, maybe this is evidence of a contagious and infectious cancer cause. And this idea really is then everywhere in the early 20th century, and what I find interesting is that it’s an idea which is often there in the negative.
So, if you look at early campaign and public education materials from the American Society for the Control of Cancer, which becomes the American Cancer Society, they are still at pains to say cancer is not contagious, and it’s also not hereditary, which they consider to be too much of a pessimistic framing of cancer. And, that’s remained remarkably constant through the 20th century. If you go onto the American Cancer Society website today, you can still find the assurance that cancer is not contagious, which indeed it isn’t, in the sense that you can’t catch cancer from somebody who already has it.
But, of course, there are a number of viruses that we now associate with cancer. And so, I, as a historian, was in this mode of having a sense of where the story ended, but then looking at people really grappling with a lot of really big questions about the nature of cancer, the nature of infection, and the nature of viruses in the early 20th century when none of these things were settled.
RS: It’s a gradual transformation. It begins with the codification, or the formalization of some of the ideas of germ theory, into microbiology and bacteriology.
And they’re, of course, the major development, as Coats postulates, as a way of experimentally linking an infectious agent with a disease. And people are trying to then take that basic framework and apply it to the growth of tumors.
Although there’s some, I think that probably Danish researchers, [Vilhelm] Ellerman and [Oluf] Bang, who start looking at this in relation to chicken leukemia. Leukemia isn’t yet considered a cancer—speaking of the unsettled nature of cancer in the early 20th century.
So, the person who really plays a major role in this is somebody working at the Rockefeller Institute for medical research named Peyton Rous. And Rous really has this fascinating, interdisciplinary background for the time, where he’s trained in both pathology, and pathologists spend a lot of time examining cancer tumors, as in the case of postmortem examination.
It’s not really a therapeutic technique, it’s a way of diagnosing what somebody died of after the fact, with training in bacteriology and microbiology, which was a forward-looking, potentially curative side of medical practice.
Rous was trained in both of those at Johns Hopkins University. He had spent time teaching in both of them. When he’s at Michigan, he’s working as a researcher at the Rockefeller Institute for medical research, and he really just wants to be able to grow a tumor in the lab.
This is a major issue for scientific studies of cancers. They can’t replicate cancer, other than waiting for it to appear, seemingly at random, in humans and animals. So, his big goal is simply to create a system for studying cancer in the lab, and he thinks that he’ll hopefully be able to get it potentially from avian tumors.
He literally goes around Long Island, which has a large chicken breeding industry, at the time feeding the city of New York, asking farmers if they have chickens with tumors.
He eventually gets a Plymouth Rock Hen, and, I think in 1909, that has a tumor, and he spends time trying to—he takes the tumor and unfortunately kills the chicken, and then grinds it up and sees if he can transplant fragments of that tumor into other healthy chickens and recreate the tumor.
And he can.
That’s a success from just having a transplantable tumor in a bird. Which had never been, no one had yet, otherwise found.
And then he goes farther, because of his training in microbiology, and he’s like, “Well, what’s the smallest part of this tumor that can really be used to transmit it from bird to bird.”
And there, he starts grinding it up and passing it through a series of basically household water filters to filter out smaller and smaller particles.
What he finds, of course, is that there is what he calls a “non-filterable agent,” something that his filters can’t block. Which means it’s got to be smaller than bacteria, which is still capable of transmitting the tumor from one generation of unfortunate chickens to the other.
And he begins, at the end of 1910, and then in some of his published work in 1911, to start talking about this as a potential tumor virus.
RS: The timeline of how we tell these stories changes, because Epstein-Barr, was identified as the result of a Scottish-Irish surgeon named Denis Burkitt, who was working in Sub-Saharan Africa in the 1950s.
And he became interested in tracing the incidence of an unusual form of lymphoma, which is now called Burkitt lymphoma.
One of the reasons that he relied on this is because in Sub-Saharan Africa, there was not an extensive diagnostic infrastructure, and unfortunately, in children who get Burkitt lymphoma, it grows very rapidly.
It creates very striking, outward manifestations. So, you don’t need to have a microscope or even a diagnostic laboratory to identify a case of Burkitt lymphoma.
He goes on what he calls a tumor safari through Sub-Saharan Africa. And then, based on the map he compiles of where these cases appears, begins to look a lot like the map of some of the infectious diseases that, at that point the Rockefeller Foundation’s Virus Research Institute, that is also based outside in Uganda, begins to suspect maybe there’s a mosquito borne infectious cause for it.
Epstein hears about some of this work, and they begin to fly samples of lymphoma tissue up to London where they’re being analyzed by Yvonne Barr, under the electron microscope. And they begin to find these small particles in the tumors that they think might be viruses.
But of course, the challenge there is that under Koch’s postulates, you would then have to reinfect people. Or reinfect an experimental organism to demonstrate those viral particles were responsible for cancer. Which, of course, mercifully, nobody was doing.
Epstein-Barr is identified as a potential candidate in the ‘50s, but it takes substantially longer, and it also takes several revisions in how we think about the causation of viral cancers to see it as a potential human cancer virus, several decades later.
By that point, you’re beginning to see the emergence of hepatitis B, and its association with liver cancer, and the papilloma viruses, and whole other families of viruses are now being considered. So, in that sense, it’s identified earlier, but the link is established, it’s a retrospective view of when the discovery was.
I think, in terms of real time, when people were discovering something and recognizing it as a potential human cancer virus, you have the work that Robert Gallo and others at the National Cancer Institute did with human tumor leukemia viruses, which end up being associated with HIV.
And then, of course, the epidemiological linkage between hepatitis B infection and Taiwan, and rising rates of liver cancer.
And those are both things that are happening right at the end of the “war on cancer,” as it’s formally known in the ‘70s.
That’s one of the fascinating things about this story is that the endings are never quite written at the moment that people are doing the work.
It’s things that people often figure out only after several more decades of study and debate and argument.
RS: There’s just such a huge variety of people involved with it. You have patients, of course, who are suffering from cancer and trying to understand what has happened to them.
You have doctors who are trying to cure cancer. You have molecular biologists who are interested in decoding the nature of life. You have activists and you have administrators—the National Cancer Institute was trying to fulfill their mandate to make people healthy.
I start my book with somebody who I only know by her first name, Joanna, who’s a young girl in Niles, Illinois in the early 1960s after the town undergoes what they think of as a leukemia outbreak.
She’s a survivor of that leukemia outbreak, which was thought to be infectious, and when a photographer from LIFE Magazine comes to do a follow up story, she insists, as a young woman, only being photographed with her back to the camera, so she couldn’t be identified, because she’s so afraid of being stigmatized as a cancer carrier. That’s the story that’s really stuck with me.
You have people like Peyton Rous, who bridge these different worlds of medicine and science and, but are still coming up against the difficulties of their own experience, which is that people aren’t catching cancer on a routine basis.
And then one of the most fascinating characters is somebody I come across starting after the Second World War, named Mary Lasker, who I’m sure will be familiar to many listeners of this podcast, who is really—people have known about Mary Lasker for a while. There’s the Lasker Awards.
But I spent a while looking over her shoulder, in her archives, at Columbia University, reading her oral histories. She is just such a fascinating activist. I think that she often is presented by doctors as a somewhat daffy, out-of-touch socialite.
But she really was this incredibly powerful and sophisticated advocate.
And she was somebody who was very invested in the New Deal. She was in favor of contraception. She was married to Albert Lasker, who was actually a moderate Republican. I think being at their dinner table would’ve been very interesting, and she listened to him, though, when he talked about the power of government money.
And she started off trying to get the federal government, after the Second World War, to pass a Manhattan Project against cancer. That failed, largely on the grounds of doctors feeling that it was too much money, and she didn’t really understand why doctors weren’t concerned with curing cancer.
She eventually becomes this sophisticated navigator of the Washington budget process. She figures out she can’t pass one big piece of legislation. She can start to remake the NCI in the image of the type of institution she wants. She quintuples its budget in the 1950s, and really instills a lot of urgency into the idea that the government should be curing cancer through research, which of course then transforms how we do cancer research everywhere.
She’s not done by the end of the 1960s when the Vietnam War’s beginning to put pressure on medical research, and people are becoming disillusioned that there hasn’t been more progress.
And she, of course is also, as a New Deal Democrat, is losing her connections to the new Nixon White House. She invents the idea, in many ways, of grassroots activism against cancer for the 1971 war on cancer.
Working with a pharmacologist from Missouri named Solomon Garb, where she really remakes cancer activism, again, from being something that was being pursued, in the halls of power in Congress, into something that was like a matter of national concern.
Her story is really in terms of both enabling so much cancer research, giving cancer research itself this moral weight that’s supposed to combat disease. I think she’s wonderful. And I have a few others that I can mention, if you’d like me to.
RS: Viral oncology has, well one of the reasons I find it so fascinating is it’s not a story of straightforward progress.
Viral oncologists spent a lot of time being confused and frustrated. Peyton Rous, for example, comes up with the idea that there might be a chicken tumor virus, and he has to wait until 1966 for his Nobel Prize, which recognizes the importance of his work.
Which I think at that point, was the single longest gap between the work and the prize that was on record.
Really, by the 1930s, most people in cancer research as a whole had stepped away from cancer viruses as a potential way of understanding human cancer. There are a few people working on it, but it’s just considered too challenging to demonstrate it, and it runs in the face of clinical experience.
Once again, people aren’t getting epidemics of cancer spreading the way that they have, and they’re very familiar with other viral epidemics. Virology itself, it’s only by the end of the 1930s and in the ‘40s that you begin to have widespread access to things, and the development of things like the electron microscope, or ultra centrifuges, or these other sophisticated instruments that make it possible for us to think about viruses in the way that we do today as actual small discrete objects.
Before these tools make them visible, they really do have this very odd, amorphous instance of, they’re not living, they’re not dead, they’re too small to be seen, but they’re also somehow still present. It’s a challenge not just for cancer virology, but for virologists as a whole.
One way that this field of viral oncology comes back in the ‘50s is through the application of these new instruments for virology that had been developed per se, working on the influenza vaccine during the Second World War, or critically, for the polio vaccine campaign, and bringing them to bear on the problem of cancer.
But, what I found when I was writing my book is that only gets you so far. There’s a Jewish-Polish refugee named Leon Dmochowski, who becomes a huge advocate of the electron microscope, and is working in Houston, Texas, at MD Anderson.
He’s taking sections of mammary tumors, and claiming to show that there are virus particles at the scene of the crime, in the words of The Boston Globe. And, at a conference, another one of his colleagues, who’s a virologist, gets up and just says very austerely, “I’d like to remind Dr. Dmochowski that images are unlabeled under the electron microscope.” And so, even these new technological devices don’t settle the debate or the skepticism that people generally have about how viruses could cause cancer.
What really revised the field of viral oncology and laid the framework for the National Cancer Institute becoming involved in the 1950s is the success of the polio vaccine campaign. And polio, once again, from our perspective, seems like a very straightforward success story, but really in the aftermath of the Second World War, there was a lot of confusion and debate as to how possible it would be to develop a polio vaccine, to culture the virus outside of living hosts—and even if it was appropriate to ask scientists to do that.
And of course, in that case, the March of Dimes, the National Foundation for Infantile Paralysis, mounted this incredibly aggressive push that resulted in a polio vaccine in a much shorter time than most scientific experts had predicted. This really feeds into the cancer virus development story in two ways.
First, it gives an overall sense of enthusiasm that this is something where you can set broad, ambitious goals and actually realize them if you spend enough money. That’s something that people working at the National Cancer Institute on cancer viruses talk about all the time.
Secondly, with the development of the polio vaccine, there’s a lot of polio virologists who are out of a job, because they basically did what they were expected to do. A number of people bring their training and sophistication in virology to bear on the study of cancer. And so you also have a movement of scientists from polio into different forms of cancer viruses, especially, initially into studying Rous sarcoma virus and various leukemia viruses in animals.
As these scientists start to work on especially tumor viruses and animals, they begin to say, “Look, what must be true of animals, will be true of humans.” We’re just waiting on our opportunity to invest in the necessary infrastructure to make that discovery.
RS: This was something that I spent a lot of time struggling with when I was writing A Contagious Cause.
I started to see that by the late 1960s, the National Cancer Institute spends an incredible amount of money on viral oncology. They eventually set up a series of programs, the Special Leukemia Virus Program, the Special Virus Cancer Program, and then just the Virus Cancer Program, which are using these managerial methods, taken from the defense department in NASA to oversee the discovery of a human cancer virus and the development of the vaccine.
This is really, really big science. It’s bigger than the Human Genome Project. My first thought was, “OK, what was the discovery, or the scientific consensus, that happened to make that program possible?” And I went back, reading the medical literature, reading the scientific literature, reading annual reports of the American Cancer Society, reading Congressional testimony, trying to find why people had agreed that this really controversial idea suddenly merited the investment of what in today’s terms would be billions of dollars in medical research. And I couldn’t find it.
I can see there are many people who are advocates of the idea that viruses are involved with cancer, but for every one of those people who’s saying that, you can find several very prominent and very potent skeptics.
Not just from medicine, from virology, from a whole set of fields. It’s a case where there’s no agreement on the actual existence of human cancer viruses before the program is created. Many people liken the virus cancer program to a moonshot. In that case, it’s a moonshot that was building a rocket for a planet people couldn’t agree was even out there.
And so, for me, this is what made it a story too, of not just science, but politics, but the most powerful thing that the National Cancer Institute and someone like the leader of this program, Dr. Carl Baker, was saying is, “We need to do science differently because of how dangerous and how lethal cancer is.” Baker was a fan of getting up at meetings and counting off in, certainly, in two minutes and three minutes and four minutes, how many people had died from different cancers, in that interval.
The argument would be that, in the face of that type of urgency, and the suffering and the mortality of cancer, we can’t simply wait to agree that there is a cancer virus and then move towards a vaccine. We need to do what they’ve done in the Manhattan Projects, what they’ve done at NASA or other defense programs, and start preparing across the whole spectrum of things you would need to do from the discovery of a virus, through the development of a vaccine and its mass production.
They need to invest in all of that all at once, even if they don’t necessarily know that there are going to be a human cancer virus, or it’s an argument, not of if the virus will be found, but when it will be found. And the answers they can only, they will only find it if they mobilize in this very big science way, far in advance of scientific agreement to what they’re looking for.
RS: You see, skeptics have many different orientations. You have major virologists, like Burnett, who are just based on their knowledge of virology, are saying, “We can’t, we just don’t have this yet. There’s no proof in terms of how I would demonstrate the link.” You have many doctors, from places like Sloan Kettering, from places like Boston Children’s who just think that the idea of a virus makes sense in reference to their clinical experience.
They’re much more interested in the possibility that there’s other causes, or they think the idea of talking about causes is a distraction from developing surgical or chemotherapeutic treatments against cancer, which they see as being the most promising way, that not thinking about what caused the virus, but really just how to treat it.
You also, especially as the search for cancer virus becomes more entangled with molecular biology, you run into a lot of culture clash issues between people who work in the clinic and people who work in molecular biology. And this disdain runs both ways.
You have people like the co-discoverer of the DNA helix, James Watson, calling clinical medicine, clinical research second-rate, or fourth-rate science, depending on which speech he gives. And you have people like Dr. Black from somewhere in New York, who says to Congress, “Why are you going to trust a molecular biologist who wouldn’t know what cancer was if they had it?”
That’s just a general added question of whom do you go to to understand disease?
You go to the doctor who has experience with it, or are you getting into these greater and greater degrees of molecular abstraction from the disease itself?
RS: This is something that remains unresolved in that part of my story. That’s the remarkable thing. The tide is a political tide. It’s partially within the push for the war on cancer of 1971 that Mary Lasker provides, which, once again, in a year or a few years, quadruples the budget of the National Cancer Institute, and gives it unprecedented authority to oversee scientific research.
In particular, expanding how much it can use contracts, which is where the government tells people what to do, as opposed to peer-reviewed grants, where the government simply gives them money without trying to control what the course of their research is.
That really gives the National Cancer Institute this broad power to conduct and sponsor research on viral oncology, despite the fact there are still many critics out there. That’s the story of the 1970s, is people doing research within the National Cancer Institute’s patronage network, and many people who feel very skeptical, for many different reasons, on the outside of that.
The thing that I find very remarkable is that despite this level of controversy, the National Cancer Institute really does make it possible to do viral oncology, and especially to start discovering the links between RNA tumor viruses, or retroviruses, and the genetics of cancer, in a way that probably would not have happened for quite a while otherwise.
RS: It’s a slippery idea, because, of course, going back to the early 20th century, vaccines sit very close to immunotherapy.
You have early efforts like Coley’s toxins, which are the idea that it’s somehow possible to engage in immunotherapy against cancer, which is also often called a cancer vaccine.
In which case, you could imagine curing a case of cancer versus vaccination as we might understand it, or certainly like the advocates of say, the polio vaccine or the influenza vaccine, or the mumps, measles, and rubella vaccine, which is a preventative measure that will prevent cancer from occurring in future generations.
In the early 20th century those are very commingled due to the fact that virology and bacteriology are not yet fully untangled. If you think about someone like Robert Koch, who identified the nature of tuberculosis as being caused by a bacteria.
He also is marketing something called tuberculin, which is supposed to be a chemotherapy for tuberculosis, based on that knowledge. That nexus makes a vaccine, for a while, also it sounds like it might be a type of immunotherapy.
But by the ‘40s and the ‘50s, a vaccine simply meant preventing it in future generations, as opposed to immediately addressing the problems that somebody with cancer would have in the clinic. Which is once again, one of the reasons why some parts of the cancer research community were less enthusiastic about it, because it doesn’t do anything for the patients that are currently suffering from cancer. It really is something that will help the next generation.
RS: I think there’s probably two big arcs that run through the story. The first is how we’ve come to understand the nature of cancer at an increasingly smaller, and smaller, and smaller scale. Moving out of the clinic and into animal organisms, animal models, into cell culture, and now into, of course, the various protein molecular mechanisms we associate with understanding how cancer works.
Understanding those mechanisms is a place for developing interventions that might be truly effective—personalized medicine, immunotherapy, things like that, and of course, a number of cancer vaccines that arise from especially the application for hominin DNA to vaccine manufacturers in the ‘80s and ‘90s. And who knows what the next generation will bring. That really moves the frontier of where we struggle with cancer into the laboratory.
The second trend is how cancer research has become bigger and bigger science. It’s no longer just one person in a laboratory, it’s whole institutions being funded by ambitious, forward-looking government programs.
Which, in turn, means that cancer research is a part of a broader conversation we have in society about—how do we deal with health and disease? What should we be prioritizing? How do we frame problems like cancer? Are they simply things that we confront in the laboratory? Are they things that we think about in terms of their social and environmental roots?
And I think that cancer vaccine research really sits almost directly at the juncture of those two different ways of talking about it. Because it is one of, vaccination as a whole, is one of these biomedical interventions that really promises immense aid to human health. If you can get people vaccines quickly enough, you can really do so much good for them. The idea of having vaccines that would be preventative against cancer is wonderful.
But it’s counterbalanced with this broader awareness that we need to keep everybody healthy, and that, as successful as vaccines are, they’re only ever going to be one part of the overall toolkit that goes into preventing and dealing with a disease as complicated as cancer. And I think that’s really where these different traditions of public health and experimental biology are still woven into how we think about cancer vaccines, cancer, viruses, and vaccination generally.
RS: I think we have a number of wonderful examples in the prevention path. When I walk around Kendall Square at MIT, the thing that of course is very exciting is the return actually to that older idea that somehow you can produce vaccines that will target cancer already active in somebody’s body.
And people generally ask these questions. I say, if I had a better sense of what the future of this field was, I’d be a biotech stock broker instead of a historian of biology. But nonetheless, I’m rooting for that idea. Let’s put it that way.
RS: I didn’t think I was going to talk about cancer at all. I came into my graduate training and the idea of what book I wanted to first write very much focused on the growth of molecular biology and how it in my naive terminology, became “big science” at some point. But wherever I turned, when I was trying to understand that story, I started finding cancer viruses.
As I mentioned, they intrigued me. I didn’t think that they, I didn’t understand what they had to do with say cellular development, or the idea that cancer even had a viral cause. I really got dragged into the topic reluctantly, but once I got into it, it’s really—I’ve kept coming back to it, and it makes me passionate, precisely because it’s so rich and it confounds so many of the normal intuitions we have about how to understand a disease like cancer.
And it also makes us think really hard about how we define success and failure in biomedical research. Which is a question that I, and I think we all have a very, how you can succeed while failing, but also failing as you succeed.
RS: I think one thing I want to stress, which I think is a very important thing to think about, as we navigate the current coronavirus pandemic, is the way that the story that I tell on A Contagious Cause is really bound up with the boundaries of nationhood. It’s the National Cancer Institute.
Mary Lasker and her allies are thinking about improving the health of Americans. But, this is also a story that discussions of Burkitt lymphoma and Epstein-Barr suggest, it’s an international story in terms of how we’ve understood the nature of cancer.
But that also goes to how we understand the nature of what it means to succeed against cancer. So, for example, in 1978, there’s a new director of the National Cancer Institute—Arthur Upton. He convenes this group of really eminent Nobel Prize winners in virology, and in chemistry, and different ways of thinking about the nature of cancer and different ways of treating cancer, to assess where they are.
David Baltimore, who at that point has already won his Nobel Prize for the co-discovery of reverse transcriptase, is sparring with Baruch Blumberg, who just got his Nobel Prize for the discovery of the hepatitis B virus, regarding the prospects of whether or not it would be possible to develop a meaningful vaccine against hepatitis B, especially given some of the new evidence that we’ve seen, that it might be linked to liver cancer.
And Baltimore is saying, “Well, look, if we really don’t understand the molecular…”—I’m paraphrasing Baltimore here, I’m not quoting him directly. “We don’t understand the mechanism by which this infection causes cancer,” which he then questions as the “devil’s viral oncology, and until we understand the mechanism better, we really can’t do this.”
And Blumberg, speaking from more of a public health perspective, says, “Well, no, we develop vaccines all the time without understanding the mechanism by which a virus actually causes disease. That’s not a problem.” They’re going back and forth.
The way that Baltimore decides to end that exchange is by saying, “Even if you could prevent every single case of liver cancer in Sub-Saharan Africa,” or maybe he says East Africa, “you wouldn’t have responded to our mandate to deal with cancer here at home.”
Because at that time, the association with hepatitis B and liver cancer was something that was being discussed in east Asia and Sub-Saharan Africa, it wasn’t really seen as a problem in the United States. And that’s where things stopped.
And of course, globally speaking, a vaccine against hepatitis B does come into the fore, and it becomes one of the most meaningful interventions we’ve been able to make against cancer using vaccines.
But, in the framework of that room, in 1978 in the United States, that’s not seen as a success. Other things are, and I think that’s an important thing to keep in mind when we think about success or failure, especially as we now are beginning to reckon with cancer, not just as the disease of developed nations, but really as a global disease.
It’s going to also require us to think very critically about how we understand what success and failure are. Not only in the absolute sense, but from nation to nation and region to region.
