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Active Learning and Research
Active Learning and Research
Environmental science and policy professor Dale Hattis studies the level of cancer risk associated with exposure to a wide variety of chemical substances. He and student Jennifer Ericson worked to compile a related database bringing together research on age-related differences in cancer susceptibility.

Meet the researchers: Incorporating individual differences into risk assessment

Interview with Professor Dale Hattis and Jennifer Ericson
Professor Dale Hattis combines biological research with statistical analysis to estimate the amount of risk people incur when exposed to a wide range of potentially toxic substances. Working with him this past summer is Jennifer Ericson, a senior majoring in both Biology and Environmental Science and Policy. In a recent interview they discussed the focus of their work.

Dale, you specialize in risk assessment and management. Could you explain what that is?

Dale: Risk assessment uses all available scientific material on a toxic substance to determine how many people are likely to be affected adversely when exposed to it. The assessment process takes into consideration things like uncertainty in the data, potential variation in amounts and circumstances of exposure, etc., in order to understand how these variations might change our expectations about the number of people likely to be affected. Risk management focuses on choices among different policies that affect risk and the likely outcomes if those policies are implemented.

For example, a government agency might be trying to decide how strictly it should regulate the quantity of diesel particulates that can be in the exhaust of big trucks. The process of assessing and managing potential risk in that situation would require many different types of information, including information about the chemicals contained in the emissions, transportation routes and schedules, and the relationship between expected effects and exposure level.

My particular part of all of that focuses mostly on how differences among people affect their susceptibility. For example, people with existing heart conditions may be more at risk than people with healthy hearts. Infants, when exposed to a particular chemical, may be more at risk than adults for some kinds of cancer. For various reasons people differ from one another in their levels of sensitivity.

What do you mean by uncertainty?

It is important to distinguish between uncertainty and variability. Uncertainty refers to imperfections or gaps in our understanding of the effects of chemical exposure. Variability refers to real differences that exist between individuals in their level of sensitivity. An understanding of these concepts involves bringing together information from several different disciplines, some of which are highly mathematical and some of which, like biology, are concerned with causal mechanisms. It's important to understand both variability and uncertainty in order to think clearly about particular risks and so that we can communicate information about those risks to decision makers and the public.

What are your current research interests?

I'm involved in several different projects. The one Jen is working on is a new effort for Environmental Protection Agency. She's helping to compile a database that will bring together information from various animal and human studies on age-related differences in susceptibility to cancer.

Most of the cancer risk assessment that's done is based on studies in which adult animals are exposed to a potentially toxic substance over a prolonged period. That's a good starting point for understanding cancer risk, but we also need to look at what happens when children are exposed, or pregnant women. How should the cancer risk assessment numbers be adjusted for exposures that occur at life stages different from those conventionally tested? And it probably depends also on the kind of carcinogen.

Other efforts are in the area of inter-individual differences for non-cancer risks. Right now there's a rule of thumb procedure for dealing with a whole host of non-cancer effects. I think it's better that protection factors be based more on experimentally-based information and the kinds of uncertainties that are involved in going from fragmentary animal data to human risk. Serious reform is needed in that area and we're trying to contribute to that.

Two other projects are extensions of some previous work on adult-child differences regarding the handling of drugs in the body, and, by extension, environmental chemicals. We're also looking at how genetic differences affect how people respond to drugs. We're doing these two studies cooperatively with the State of Connecticut for the Environmental Protection Agency.

By systematizing the existing scientific literature on known responses to drugs, we may be able to make an educated guess about how people might respond to some related but untested substance. Pharmaceutical studies are particularly valuable because they involve testing on human subjects and careful response monitoring.

So testing of potential environmental toxins uses animal subjects, while drug testing, after the initial animal trials, also uses human subjects?

Yes, and sometimes we even have information on how drugs affect different age groups. One of the drugs that we're studying intensively is caffeine. Caffeine, it turns out, is metabolized in the liver by a particular enzyme that is very slow to mature. Very young babies have very little of this particular enzyme, so that it takes them about 96 hours to eliminate half of this drug whereas it takes adults only a few hours. That finding could, if relevant to some other environmental chemical, cause a big difference in susceptibility. We want to understand how to make inferences about untested substances from data that are easily gathered in laboratory experiments that don't involve direct human testing.

Jen, tell us about the project you're working on.

I'm working on the project about differences in susceptibility between various age groups. I'm collecting research on studies using animal subjects and adding it to a database for later analysis. I'm focusing on studies that involve exposure to chemicals that cause damage to DNA.

Dale: Because the chemicals in these studies are administered in known amounts, we can examine the amount of effect per unit of dose when administered to animals of different ages. And we can also look at how rapidly animals of different ages repair some of this damage. We get an idea of the size of difference in susceptibility between older and younger animals.

Dale, how might people be exposed to these particular chemicals?

In a variety of ways. Some could be airborne particles, some might be molds that grow on different food products, particularly grains, some result from the way food is cooked.

So, Jen, you're looking at studies that have already been done and trying to bring that information together.

Right.

How did you end up working with Dale?

I had him as a professor in Cancer: Science and Society during last semester. I was looking for a project to do for my Capstone Seminar for my Environmental Science and Policy major. Professor Hattis had talked about his research on cancer susceptibility and I thought it sounded interesting, so I followed up on that.

Can you talk about participating in research versus more traditional classroom learning?

I think it's going to help me later on in my class work. It's added a different dimension that has definitely helped. I found this summer to be a really great experience.

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Jennifer Ericson and Dale Hattis
Jennifer Ericson and Dale Hattis


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