Louis Guillette Jr., endowed chair of Marine Genomics at the Medical University of South Carolina, recently won a Heinz Award for his groundbreaking studies on how toxic chemicals impact reproductive development and functioning.
Below are excerpts from our recent interview.
You're a leader in the field of the impact of toxic chemicals on the reproductive systems of wildlife. What got you into this field?
By training, I'm a reproductive biologist. Although people in a certain area know me for the environmental toxicology work, I've spent 30-plus years trying to understand how the environment, in all of its aspects, influences the development and functioning of the reproductive system. I started the early part of my career working on, for example, high-altitude pregnancy. I've always been interested in environmental variables -- from temperature and altitude to nutrition and contaminants. I started to realize we can't study contaminants out of context with all these other variables. Whether you get an adverse response to some environmental perturbation depends on other things. Even in humans, lifestyle matters. We use whatever species is appropriate to address the questions. If we're studying high-altitude pregnancy, we work on animals that give birth to live young at high elevation.
My story on contaminants: I started at the University of Florida in 1985. I was working on environmental variables. A couple of colleagues from the state and the U.S. Fish and Wildlife Service were trying to understand the reproductive biology of the American alligator. We started in about 1986 what I thought would be a straightforward two-year project. We're now 20-some years later. This animal made an important sentinel species to tell us something about the health of the environment.
Why are alligators considered a sentinel species?
Sentinel means to watch and warn. We used to have sentinels on the walls of medieval towns to warn about impending disasters. Sentinel species have to have some of the same attributes. They have to stay in a spot, so they are telling you about that spot. Alligators basically stay within a half-mile of where they were laid. They're top predators. If you think about accumulation of contaminants in an environment, they're the ones accumulating these through the whole food chain. You could see effects because they're going to have higher levels than, say, little fish.
Alligators have environmental sex determination. When the egg is incubated at a certain temperature, I can produce all sisters or all brothers. I can make every egg a female. Now I can begin to understand the interaction, for example, between the genetics you inherit and the environmental impacts. I can take those sisters or brothers and put them under different experimental procedures, but I know they all came from the same parents. It's powerful.
What does this have to say about people? Alligators do some things differently, but there are also similar things. One thing I don't think people appreciate is something in the field of biology called constraints. There are only so many ways you can make an ovary. If you look at all the animals in the world, ovaries are ovaries. Their structure, how they work and their genetics are tremendously similar. You have to understand in a sentinel which things are similar and which are different. By understanding the similarities and differences, you can start to [determine whether] these animals tell us something about human health or just about environmental health.
My main job is to understand what's normal in a species and how the environment influences the species to lead to an abnormality. The next step for me, if I see an abnormality, is to ask if that tells us anything about potential health effects in humans.
What abnormalities are you seeing in alligators and other wildlife?
The most famous one, which probably made the biggest impact in Washington, was that alligators from contaminated environments had small penises or abnormal genitalia development. Abnormal genitalia development in baby boys is one of the most common birth defects. It's not pure genetics. The large percentage of them have to do with some environmental perturbation. We found this was the case in alligators. We started a series of studies to understand how the environment influences genital development.
Another abnormality we found appeared to be, at least initially, structural abnormalities in the ovary. A normal ovary will have ovarian follicles. In each, there should be one egg. The egg is surrounded by support cells. The cells around the follicle make estrogens and progestins. These are the hormones critical for menstrual and reproductive cycles. We know if a developing female is exposed to some abnormal estrogen signal, whether it be a drug or environmental chemical, you could increase the frequency of these abnormal follicles. In the mouse world, that leads to infertility. In other cases, the egg can be ovulated, but it dies in early development. Up until we started doing our work, this condition was largely associated with giving a developing mouse or human a pharmaceutical estrogen. All of a sudden, we came along and said, 'Alligators aren't getting drugs from their physician, so where is this coming from?' Our studies were some of the first to document real world effects of environmental estrogens.
Are agricultural chemicals the main culprit of these reproductive problems?
For us studying specific lakes, largely what our animals are being exposed to are agricultural chemicals from runoff. But in the real world of humans, there is a wide array of chemicals. These are from personal care products and other products. They're not just from pesticides in agriculture, but potentially chemicals used on lawns and golf courses. Everyone wants people like me to point to a chemical. It's not a chemical. It's a mixture of chemicals. It's this complex environment, a combination of lifestyle and contaminant exposure and some genetic predisposition you inherit.
When I give public talks, my response to this is moderation. Do I drink out of plastic bottles sometimes? Of course. We all have to. But do you have to spray your house every month if you've never seen a bug? Many of those chemicals are persistent and have not been tested for the kinds of outcomes we study.
How has your field changed over the past few decades?
When we started working on this in the early 1990s, we were one of just a few labs. To say we got a lot of criticism, even from our own colleagues, is an understatement. We were constantly told, 'This is just a hypothesis.' Some of the criticism was good. Some was completely based on vested interest. We all want children that are healthy. At the same time, the degree of assurance you need to change your mind is influenced by your vested interest.
There's a sense that you don't have to be a scientist to be worried about stuff being dumped into the environment. That's grown. Some of it is good, but some is taken out of context. You have to be realistic about what's going on. We have built into us some resistance. We've always been exposed to toxins. Our livers are designed to detoxify things. Our livers are not designed to detoxify 40,000 chemicals they never saw in the real world. Those are synthetic chemicals that in some cases are designed to be resistant to degradation.
There are more scientists convinced these are real issues that have to be addressed. Science, by nature, is a debate. We're trained as scientists not to focus on what we know. Our goal is to move the unknown forward and make it known. When you hear scientists disagreeing, you have to ask if they're disappearing on the main principle. For us, nuances are critical. We know we can show changes in gene expression, how an ovary develops, how an organ system works. The question is: When does that change become disease?
What's next for your work?
Every study generates more questions. We keep trying to understand this. My biggest concern and intellectual question is how to account for all the complexity that exists in the real world in someone's life. It's the stress of a job and being a parent. It's the changes in nutrition and the contaminant exposure. It's the genetics you inherit. How can we put those together to understand which variable are critical in predicting whether you'll have health or disease?
The problem we've had, and I think we'll continue to have, is our country regulates chemicals one by one. Many of these chemicals are made by different companies. We regulate them one by one with the assumption that the average person is not going to be exposed to 27 other chemicals made by other companies that potentially have similar effects. The problem is how to take real world exposure -- this complex mixture people see everyday -- and put it together in some way to get a sense of the health consequences.
Photo: Louis Guillette Jr.