Dana Dolinoy, environmental epigeneticist

Lead exposure has long-lasting health effects. This researcher is studying how it changes our genes. Interview by Laurel Hamers

April 04, 2016

Dana Dolinoy in her lab at the University of Michigan School of Public Health. Photo: University of Michigan

The lead-poisoned city water in Flint, Michigan has sparked a national furor. It has also brought attention to the way that the heavy metal works its way into our bodies and settles in our bones and soft tissues. That buildup can trigger a lifelong suite of health problems, including developmental delays and behavioral challenges.

Dana Dolinoy, an associate professor in the University of Michigan School of Public Health, is looking at the way lead exposure changes our genes.

Dolinoy studies environmental toxicants like lead and bisphenol A (BPA, found in hard plastics) and their effects on our epigenome—the molecules that turn our genes on and off like light switches. An epigenetic modification is different than a genetic mutation in that it doesn’t alter the actual DNA code that makes up our genes. Rather, it changes when and where in our bodies those genes become active.

The epigenome helps our cells specialize early in life, turning on programming that directs them to become lung cells or muscle cells or skin cells. But our life experiences continue to modify our epigenome even after childhood. Exposure to toxicants like lead or BPA can cause changes that persist across generations. But there’s hope, too: Dolinoy and other researchers have found that factors like a healthy diet or a low-stress environment can counteract those negative epigenetic effects.

Dolinoy carries out both shorter-term studies in mice and longer-term studies in humans, some of whom she and her colleagues have tracked since birth. She spoke about her research at the February 2016 meeting of the American Association for the Advancement of Science in Washington, D.C. After her talk, she sat down with SciCom’s Laurel Hamers to untangle the epigenome.

In your talk, you made an analogy to the genome being the hardware on your computer. If so, then what’s the epigenome?

The epigenome is the software. Most computers have one hard drive, but you have hundreds of software programs on there. We have one genome, but we have hundreds of different epigenomes because we have about 200 different cell types. So you need them to work together.

Why are you interested in studying the epigenome?

The genome is stable and non-modifiable. There’s not a whole lot you can do about a genetic mutation that you inherit or one that is spontaneous. But the epigenome is dynamic. So we have some hope. We can potentially use epigenetic biomarkers [measurable indicators of where changes have occurred] to predict who might develop a disease later in life and intervene to protect that individual.

Is your work more on uncovering the way the epigenome is modified, or on creating solutions? 

The vast majority of our work is on characterizing when, where and how the epigenome is affected by environmental exposures. That’s a really important question in the field of epigenetics. It’s really new, so we need to do these important baseline studies.

But the bigger question is, well, what are we going to do about it now? There are a few FDA-approved epigenetic drugs for certain end-stage cancers that have been effective in prolonging life for months, but they have a lot of bad side effects. So what you’re doing is you’re giving an individual a [drug that changes] their entire epigenome. And that’s actually bad because whether [that change] is a good or a bad thing really depends on where it’s happening.

So the new part of our research is trying to develop tools and technologies to target specific parts of the epigenome.

How do you pick which environmental toxicants you’re going to look at?

In mice, we can look at them one at a time. We can look at BPA, we can look at lead, we can look at phthalates [used to make plastics soft and flexible]. But we can also put them in combinations. We know from our work in the birth cohorts that [people] are exposed to these different things at different levels. So from going back and forth, we feel like we have the most power to identify which exposures at what time are having the greatest impact on the epigenetic programming.

As in, exposure to multiple toxicants could play off each other and have effects that exposure to one of them alone might not?

Right. Are they additive? Are they synergistic? Which means that one plus one is more than two.

One of the things we’re really interested in is whether diet mitigates or exacerbates the effects. Having a good diet could counteract the effects of the toxicant [on the epigenome]. We’re looking at particular types of high-fat diets.

"A less stressful environment, a sense of strong community—that can also get under our skin as well."

What have you found there? Today you talked about how the effect seemed reversible, which was really cool.

Well, our high-fat diet work isn’t yet published. But actually, diet has a much bigger effect than the toxicant exposure. So that’s really important, because there’s a lot of focus on toxic chemicals. There’s a lot of focus on having a good diet for obesity reasons. But I don’t think we’ve really thought about how they can work in combination.

Like a good diet actually makes you healthy even if it’s not a matter of controlling your weight?

Yes, exactly.

How do you think that intersects? For example, you have a population of mostly low-income people in Flint being disproportionately affected, and they don’t necessarily have access to the best nutrition either.

I think Flint is a tragedy. We have a lot of work to do. But I think it opens the door for us to think about how we have to invest in public health education. Flint is not the only place where these things are occurring.

I’m not stating that the Flint population has [undergone] an epigenetic change. But if lead does impact the epigenome, the same sort of things we’re talking about in [mice], like good nutrition, may actually help prevent those negative effects.

There are also a lot of interesting studies that first started in animal models about social structure. If you have good family and home and neighborhood environments, this can help buffer against the negative effects of neurotoxicants. A less stressful environment, a sense of strong community—that can also get under our skin as well.

How do you think other communities where lead might be lurking can avoid having it turn into a crisis?

Flint has gotten a lot of attention because of exposure through the plumbing and the water. But the same old housing structure that has lead pipes also has lead paint in it. So it’s important that we get the word out that there’s dust in the house and other potential exposures through soil that families must be protected from. When lead gets in, [the body] doesn’t care where it came from.

It’s important to speak up like the people in Flint did. Often there aren’t enough resources in a community health department to fully educate the community about exposures. Maybe this will be one good outcome from Flint: We’ll realize these are positions we need to fill.

How do you go about testing this in humans? Do you rely on populations that have been heavily exposed?

There has been emphasis in the past to look at very highly exposed populations. But we’re more interested in general population levels. Unfortunately, we’re exposed to lots of things. You name a chemical and we can measure a range of distribution. For example, through national models [from the Centers for Disease Control], we can say that 93 percent of humans have detectable levels of BPA in their system.

When you do work in mice, how do you know if you’re exposing them to a dose that’s going to correlate to something—a level that’s reasonable for humans to be exposed to?

The dose level is really interesting. You can measure the levels in the mouse mother to see that they correlate to levels seen in humans. We’ve done that, but rodents metabolize chemicals in different ways than humans. An animal model is a model. It’s not always going to perfectly mimic what’s would happen in human populations. For example, with BPA, there are two major detoxification pathways. Rodents use more of one and humans use more of [the other].

There are a few other nuances, too—the timing of exposure and the route of exposure. We really make sure we start pre-conceptually, because we know that it’s those first few days of pregnancy when [epigenetic modification] is happening.

One thing that has shocked me about BPA is that when the dangers started coming out, all the water bottle companies rushed to make their products BPA-free. But it seems like it’s still lurking everywhere.

Yes, and it’s potentially a missed opportunity, right? We think that the early pregnancy exposures are changing the epigenome. [But if you] change just the water bottles or even the baby bottles, you’re missing [the bigger picture]. You’ve really got to focus on the pregnant woman. And that means you’ve got to think about every exposure source out there.

So how could a pregnant woman best minimize her exposure to BPA without locking herself in a closet for 9 months?

Which I don’t recommend, because it’s really stressful [laughs]. I’ve gone through two pregnancies. I really advocate keeping your stress level under control about this. There are certain things you can do. You can [avoid] microwaving plastic. You can eat fruits and vegetables and minimize your use of canned foods. But even if you did everything right, you’re not going to 100% eliminate your exposure. The idea is to buffer this with a healthy diet as well.

How you communicate that to the public in a way that adequately conveys the risks or benefits without sensationalizing them?

It goes back to the adage of doing everything in moderation, right? There’s a whole list of things that are potentially “good” for your epigenome. But to get the amount of [beneficial compounds] out of red wine that you need, you’d have to drink gallons of wine. So that’s not good either.

That ties back to what you were talking about before with environmental justice issues.

Yes. You can’t expect that it’s an individual’s responsibility to eliminate their exposures.  That’s just never going to be feasible. So it’s now about thinking about how to get this into the policy realm. It’s really important to communicate, which was not done well in Flint.


© 2016 Laurel Hamers. Switch yourself on to Laurel’s writing at laurelhamers.com.