Newswise — In order to find answers about cancer, you have to start with the right questions. Questions like, how does obesity contribute to cancer risk? And why don’t more people alter behaviors known to increase the risk of cancer? Now in its second year, the National Cancer Institute’s Provocative Questions Project has assembled a list of 24 cancer research questions. The questions are not intended to represent the NCI’s full range of priorities in cancer research, but challenge cancer researchers to investigate new areas that may require more in-depth study. According to Dr. Harold Varmus, Director of the National Cancer Institute, “science is progressing so rapidly. We are uncovering new observations that need to be pursued. We are looking at new questions that we never satisfactorily answered in the past.”
Each Provocative Question investigates how cancer is caused or could be prevented. And each question has the potential to lead to major discoveries and advance future oncology research. With recent advances in fields such as biochemistry, molecular biology and genomics, the Provocative Questions initiative hopes to bring scientists together in a variety of disciplines to build upon recent innovations and address perplexing, neglected questions.
In 2012, 57 grant recipients were tasked with attempting to answer one of 24 Provocative Questions. Applications for the second round of Provocative Questions grants are due this spring. Ed Harlow is Senior Advisor to the Director of the National Cancer Institute and has played a pivotal role in the development of the Provocative Questions Project.
Ed, how did this idea come about?It’s a Varmus idea. It’s something that he discussed with the community when he was inaugurated as director of the Cancer Institute. It was stimulated by his appreciation of other community-based efforts to try to identify important problems in the world. The most recent example of this is the Gates Grand Challenges, started by the Gates Foundation. Their challenge was to come up with a mechanism to ask the field, “what are the most important challenges for global health?” They went to the community at large and they got a huge response. Harold was part of that group. He was savvy and into ideas about asking the community to self-identify problems they thought were really interesting.
So, you decided to talk to the cancer community?We don’t ask the community often enough about what’s important and what’s interesting. Harold’s take on this, unlike the Gate’s operation or some of the other prize challenges, was that this should be a question-oriented project. It was important to actually form a research question out of the discussions. Forming a workable, important question turned out to be an important aspect of why the whole Provocative Questions process works. The other thing we agreed on, that we pressed on, was that we were not interested in looking at areas where we were already strong, where we were making progress. The idea was to look in areas that we weren’t doing so well in.
How are the questions generated?There are two ways that the questions are being generated. One is open to anyone in the world. There is a Provocative Questions website and if you register on the website you can propose a question. Or you can comment on somebody else’s question. So, there is an open access vehicle that anybody, anywhere in the world can come in and say, “This seems to be an important thing we should be working on.”
The other thing we have been doing is running what we call PQ workshops, which have turned out to be interactive discussions. They are one-day long with about 20 to 25 people, typically experts, sometimes organized around themes. We typically spend some time discussing the PQ process, what has worked and what hasn’t worked. Then, individuals take turns proposing a question and everybody gets a chance to discuss it. You are talking to colleagues, some you may know, some you may not know. You may have completely different backgrounds. They challenge you right off the bat and we begin to shine a light on some areas that deserve some attention.
What are the parameters for the questions?We came to a few, pretty simple, basic rules. One is that it had to be something that we were not working on. It had to be something you could do now. These weren’t pie-in-the- sky questions. You had to be able to imagine at least one or two ways to do those experiments now. They had to be practical. And they had to have some sort of compelling expectation that if you succeeded, you would have added to our body of knowledge. The rest of it was how would you put this together, mechanically? What’s the framework? What’s the organization? And there, we are still learning. We are still experimenting.
What makes a question provocative in cancer research?It is definitely worth saying something about the name, because it suggests that we are asking the questions to be provocative, when, in fact, the questions might be mundane. They might not be provocative in the way that you would think. It is not about the quality of the question, but the quality of the research. In the first workshop, the initiative was actually called Big Questions. Very quickly, people realized that was a crazy name because you didn’t actually want the questions to be big. Small questions could be equally good. We needed a name that made sense and provocative was the one that stuck. It is still not completely correct. It is about whether the answer to the question will give us this drive. That is what we are defining as provocative.
The goal of the project is to stimulate provocative research?The idea here is to stimulate great science on problems that need to be solved that people are not paying attention to. That is obviously the most compelling reason to do this and the most tangible outcome that we would like to have. But there are other advantages. I think the field as a whole doesn’t get the opportunity to talk and argue about science that often in this kind of framework and this is a way for them to come do it. So, it gives them a chance to get together and say, “Whoa, that is really interesting. I hadn’t thought about that.”
What changed in the second round?In the second round we rewrote some of the questions, we added some new ones, and we retired about a third of them. Those were all questions it was clear the field got and they were working on and we didn’t feel like we needed to stimulate that area anymore. We rewrote a third of the questions to make them more clear and precise, and a third of the questions are new.
What do you hope to see in the second round of applications?I would like to hope that the applications got better overall, that when you read them this next time you think, “Oh wow, that is amazing.” The first time, we got every type of application you could imagine. There were some people who were just trying to shoehorn their current research into one of the questions. They were recycling their ideas. And then there were people that went about these in completely new ways. They switched fields or they were using their field in a brand new way. Those are the really innovative ideas. But there are all sorts of different approaches.
Has the program been well-received in the field?I think people like the idea of having these kinds of questions out there. There has been a very strong response from advisory boards and groups that have had a chance to comment. We obviously got a lot of applications. The approach has also been picked up by other institutes and groups. That has happened in a couple different ways. Individual cancer centers have started doing the activity locally—building questions locally, on their own intellectual framework and their own funding. Other institutes have decided to replicate some version of it, either with bigger questions or smaller questions. And some groups are using the questions in teaching. These are interesting questions of today and can be used as a framework to discuss science with students.