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Interviewer: It's estimated that half of scientific studies are irreproducible. They can't be replicated and this is a problem. Today, we're talking about a case study in irreproducibility, up next on The Scope.

Announcer: Examining the latest research and telling you about the latest breakthroughs. "The Science and Research Show" is on The Scope.

Interviewer: I'm talking with Dr. Heidi Hanson from the Huntsman Cancer Institute in the Department of Family and Preventive Medicine at the University of Utah. It's been estimated that up to half of scientific studies are irreproducible. They can't be replicated and this is a big problem. Dr. Hanson, you've actually published a study that feeds right into this conversation. The study calls into question a correlation that has gotten a lot of attention in the past few years.

Dr. Hanson: It's previously been reported that cancer and Alzheimer's disease have an inverse association. So basically, what's been said up to this point is that if you have cancer, you're protected from getting Alzheimer's disease later in life. If you have Alzheimer's disease, it protects you from having cancer.

Interviewer: And this got a fair bit of attention. There was a report in USA Today, there were reviews and nature of reviews, neural science and several other publications. How did the authors of those studies come to that conclusion in the first place?

Dr. Hanson: There have been a couple of studies where they've looked at individuals that have had cancer, and followed them for a period of time, and look at their Alzheimer's disease risk. And then, they also look at patients with Alzheimer's disease and look at their cancer risk later on in life. It's been published using a couple of bigger studies. They did the normal statistical methods that you might be doing just to come to that conclusion.

Interviewer: So basically, for those people who have cancer, fewer of them are found to develop Alzheimer's disease?

Dr. Hanson: Yeah, that's correct.

Interviewer: And what about that result set alarm bells off for you?

Dr. Hanson: I'm trained to think a lot about selection, and in particular, mortality selection. So what that means is I think about how processes that lead to different rates of death can affect the results that we see. And part of my demographic training is to think through some of those things. So I'm constantly looking at a result and asking if I really think that that's what's going on or if there is something underlying the result that we're seeing. So yes, it may be what the data is telling you, but is what the data is telling you actually what's going on? Are we missing something bigger?

Interviewer: Keeping that in mind, what was it that you found in your study?

Dr. Hanson: Our study replicated some of the previously reported results. And then, we showed, once you start to think about these things, and think about how mortality is affecting the rates of Alzheimer's diagnosis in these patients, you actually see a different story. It's not that there is not that inverse association that exists, but it's that mortality is driving that inverse association. It's not because there is some underlying cellular genetic mechanism underpinning both diseases. It's because if you have cancer, you have higher mortality. You're not going to go on to live long enough to be diagnosed with Alzheimer's disease.

Interviewer: It certainly makes sense. And that's actually really important, you've said, when you're thinking about aging-related disease and the aging population. Can you talk about that a little bit more?

Dr. Hanson: Yeah, absolutely. So when we're aging, there's a lot going on. You aren't usually suffering from a single chronic disease. There are multiple thing going on at the same time. And if you think of aging in a single context or aging with a single disease and you're ignoring all of those other things that are going on, you're missing the bigger story.

Interviewer: Do you think someone could come along a few years from now and find that maybe you didn't consider something in your analysis?

Dr. Hanson: Absolutely, and that's why I like science so much. We're not coming up with the best answers all of the time. It's an iterative process. We should all be considering each other's work, and we should all be critical of each other's work and figuring out how we can really understand what's going on. And to do that, it's necessary to be critical and to try to decide, okay maybe if we look at this a different way, we will be seeing something else. So maybe there is this underlying mechanism and if we're able to look at it this way, we can get more into what's going on. And that's what should be happening.

Interviewer: Yeah, that's a really good point. I think one of the issues that you had brought up is that you're really trained to really look at the data and consider all the factors that might go into some of these correlations or some of these results. What do you think can happen to make sure that some of these people who are trained in the life sciences might consider some of these other types of analysis or other types of questions?

Dr. Hanson: Yeah, one of the biggest things that I think can really help that is working interdisciplinary. If we are working across our own disciplines, naturally we are trained to think different ways, naturally we're going to approach problems from a different direction, and naturally we want to start to question different things. Things where I've been trained to somewhat ignore them through my training, someone else may look at the same problem and say, "Wait a second. You're not thinking about this. You need to be really critical of this."

And that's what's so fascinating and fun to work with individuals from different disciplines. It's how really good science is done, in my opinion. And really good science can't be done without that difference of thought. I think it's absolutely necessary. And I'm seeing a lot more of it, which is exciting.

Interviewer: So do you think this is a common problem that people aren't considering their questions carefully enough?

Dr. Hanson: I do. I think it's a very common problem. I think that people find the results that they're looking for a lot of times, and I think that's unfortunate. And I think that publication bias leads into the kinds of problems that we are seeing where people are only reporting certain things or things are only getting published if they are of interest to the public. I think that causes problems. I also think the really big push to publish fast causes huge problems. And it's unfortunate.

People just aren't as thorough with their statistics, with their methods, with their thinking through the problem as they should be because there's such a push to get the publication out. It's this huge push. Everybody wants to move things quickly, do one analysis and send it off. And that's what you do. And I think it's unfortunate.

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Interviewer: Getting a better understanding of the long-term effects of poor air quality in Utah. That's next on The Scope.

Announcer: Medical news and research from University Utah physicians and specialists you can use for a happier and healthier life. You're listening to The Scope.

Interviewer: Heidi Hanson is a researcher that studies poor air quality and its adverse health effects. Heidi, when you look outside on one of our inversion type days, knowing what you know, what goes through your mind? Because I'd imagine it's a little different than what goes through my mind because of what you do know.

Heidi: Yeah, so I know that it's not great to be out there and it concerns me for a lot of the populations, especially the long-term effects of it. If a child's being exposed in utero, what are the long-term effects of this bad air quality? I'm thinking a lot further down the road. We also want to think about, obviously, our young children are a sensitive population and then older individuals as well.

Interviewer: Why young children? Is it because they're still developing?

Heidi: Yeah, yeah. So they're sensitive at the time of the exposure, but they're also sensitive for other reasons as well. So they're going through a period of development and so any environmental exposure to them may have long-term adverse effects. Because they're still developing, they're still growing their . . . environmental shock may really affect them in a long term and what we call that is a critical or sensitive period. When a child in utero, or is a fetus, they're going through a lot of rapid development at that time and any sort of environmental shock or exposure can change the way that they're developing.

And what we call that is scarring. Basically what that is, is that's a change to them that cannot be reversed. And for childhood, we usually we call it a sensitive period. So it's not quite as a critical growth period, but it's sensitive to environmental exposures, a lot more sensitive than an adolescent or an adult.

Women are another population that may be affected more than men by the poor air quality. And so that's something that's very interesting to look at the sex differences and really understanding if women are, what are those mechanisms? Then, another population that I've been working on with Dr. Anne Kirchhoff and Dr. Judy Ou at the Huntsman Cancer Institute is looking at cancer survivors. So trying to think through how cancer survivors are affected by bad air quality as well.

Interviewer: I guess I'm fairly fortunate the fact that I'm a male and I'm an adult and I don't have respiratory issues so, quite honestly, a lot of times I go out and I can smell the air, and I can see the air and I don't like the air, but I don't know that it affects me, really. Is that accurate or is it, "Oh, yes, it affects you, Scott"? What's your answer to that?

Heidi: I think it probably affects you a little bit more than you realize. So yeah, you may not have an asthma event or an asthma attack, but it's really . . . I don't know if you've noticed your nose running a little bit more or your body reacting because there are foreign materials going into your body that it's not expecting to deal wit. And your body does have to deal with them in some form. Even though you're not having an event that's taking you to the hospital, it's still affecting your health in some way.

Interviewer: Yeah, that would make sense. You look out and you look at that air and you go, "That can't be healthy," and the research shows that that's indeed the case?

Heidi: Absolutely. There is so much research on this topic and I really think it's pretty hard to refute that there are adverse health effects that are associated with air quality just because of the volume of research that's pointing to this. Not only is it just epidemiological research, but we're looking at animal models and you're seeing the same kinds of things. We're seeing there are definite effects to their quality. Even things you wouldn't necessarily think of, like your fertility. We're seeing there are studies out there showing that bad air quality may affect semen quality in men or bad air quality may affect fecundity for women. It's not just like your normal things, asthma, cardiovascular disease, but it may be affecting a lot more than just that.

Interviewer: And other stuff that we don't even realize.

Heidi: Right.

Interviewer: I know when you're doing research, when you're dealing with anything environmental, it can be very difficult because there are a lot of things in the environment. When you're looking at the effects of air pollution on the populations you're looking at, how do you know that it's air pollution that's causing it? How do you figure all that out?

Heidi: Yeah, so that's extremely difficult. A lot of what we are doing is with some of the methods we can do so you're comparing an individual to theirself in the statistical methods that we're using. And so what that does is that pretty much makes it so that anything we're not able to observe is kind of taken out of the equation. Basically, we're looking at the only things that are changing for that person on that day is their exposure to the air quality.

Air pollution is this amazing thing in Utah so we have this natural laboratory for doing this type of work where we have very clean air days and we have terrible air days. It leads to a kind of a perfect set up for this kind of research where there are strong environmental exposures that are well documented to have. There are biological mechanisms that are plausible that make us think this really may go on to have later life effects.

Interviewer: How do we get to a point where more people care? How do we get to a point where somebody . . . do you feel that we get to a point where somebody like me goes outside and I go, "This is terrible. We've got to do some about this," and then goes on with their day to day? Versus the people that are passionate about it are trying to make change. How we get more people like that?

Heidi: I think people really need to understand that this not just an acute effect. It's not something I'm only dealing with today and then tomorrow it's gone and it's okay. But if people really start to realize that what they're being exposed to may affect them now. It has potential to affect them long-term, especially when they start to get older. But not only that, it really has the potential to affect multiple generations.

If people are concerned about the health of their children and their grandchildren, they should be concerned about the air quality right now. There are studies that are just starting to come out showing there may be epigenetic changes related to air pollution. Basically, what they're saying is that air pollution may affect you, but it also may affect your sperm, which may go on to affect your children, or your grandchildren, or that exposure in utero may lead to epigenetic changes that go on to affect that child and also that child's child.

This is all newer research and so that has to be considered when you're thinking about this. But there is potential that this goes on to affect generations and it's not just that the only person that's affected it's you on the day of bad air quality.

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