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Taking the Long View

Researchers lead revolution into how chemicals impact environmental health

by Dawn Brazell
Public Relations

On the surface, crocodiles in the renowned Kruger National Park and the oil spill along America's Gulf Coast may not seem to have much in common — unless you're MUSC researcher Louis J. Guillette Jr., Ph.D.

The reproductive endocrinologist and a developmental geneticist is involved in studies in both regions to figure how chemicals and contaminants interact with the environment in ways that impact human health. His research is confirming just how dramatic and far reaching these impacts can be.

                                  GuilletteDr. Louis J. Guillette in South Africa. Watch a video at

That's a subject Guillette, director of the Marine Biomedicine & Environmental Sciences Center, explores in a reflective piece published in Science magazine titled "Life in a Contaminated World." (

The article commemorates the 50th anniversary of Rachel Carson's book ,"Silent Spring," that challenged thinking that up until the early 1960s saw pesticide use as simply a benefit to agriculture and public health with few detrimental consequences. Guillette observes in the article that the book was the start of a debate that continues to this day on the relative benefits and risks of not just pesticides but of all synthetic chemicals.

Guillette shows off his 'Rachel Carson was right' button.

His goal: To get researchers, doctors and the public asking the right questions.

"It's time. A revolution is taking place. The new realization is that your health is a combination of what you inherited from mom and dad, but also the environment you saw from the day you were conceived. It's no longer diseasecentric in that you have a mutation and it's a predisposition for disease," he said, adding that a person's diet and lifestyle, level of stress and exposure to chemicals that act as endocrine disruptors all could be factors leading to such conditions as diabetes, obesity, cancer or infertility.

"It's not just your genes. The idea is there is far more you in your health than just what is inherited from mom and dad. Your daily actions actually have a much greater impact, not only on your health but the health of your children and even your grandchildren. This potentially has a multi-generational effect."

The reason Guillette is so passionate and gives dozens of public health talks every year is that he sees the impact of how chemicals and environmental contaminants can mimic hormones and act as endocrine disrupters.

Endocrine disruptors can create issues from infertility to obesity by mimicking the actions of naturally-occurring hormones in the body or preventing the hormones produced. An example is how the liver handles excretion.

Researchers are studying compounds that act as obesogens that encourage the body to store fat and re-program cells to become fat cells or the liver to become insulin resistant.

In his wildlife biology research for the past 20 years, Guillette has found infertility and reproductive issues in alligator populations from Florida to South Carolina. Mammals use hormones that are identical to what reptiles use, which is why alligators and crocodiles serve as typical research subjects for Guillette as sentinel species to study environmental impacts on human health.

Into the Wild
Guillette was asked to go to South Africa to Kruger National Park to examine why almost half of the crocodile population there has died off in the past two and a half years. He went in September for a couple of weeks to catch and test crocodiles, getting chased by hippopotamuses and driving through maternity herds of elephants.

Dr. Guillette, who traveled with armed guides while doing research in Kruger National Park, took time to photograph the wonders of the region.

"You would come around a bend and there would be a lion. It's like being in Africa 100 years ago," he said.
It was, except that this area is a low-lying drainage basin and the crocodiles are in trouble, as well as catfish. "I do know crocodilians, and there are some things that don't measure up. Something is going on. The park is an environmental wonderland, a place that people come from all over the world to visit. It resembles New Orleans as far as environmental problems in that it's a low-lying area susceptible to contaminants that are transported in rivers from all over the country."

Guillette said the initial four year study in South Africa will be an interesting collaboration, as will be the three-year BP trust fund-sponsored Gulf of Mexico research grant. Guillette and colleagues Demetri D. Spyropoulos, Ph.D., Satomi Kohno, Ph.D., and John E. Baatz, Ph.D., landed a $1.2 million grant from the Gulf of Mexico Research Initiative to study the effects of the Deepwater Horizon oil spill on the gulf.

The study, "Using Embryonic Stem Cell Fate to Determine Potential Adverse Effects of Petroleum/Dispersant Exposure," involves the latest in innovative testing methods that takes advantage of where the researchers have set up shop.

Although the Hollings Marine Labarotory is a National Oceanic and Atmospheric Administration (NOAA)-administered facility, it is a fully cooperative enterprise with activities governed by the five partner organizations that include MUSC and the National Institute of Standards and Technology (NIST).

"It's not just great science we're proposing, but it is also the setting that provides us a step up compared to lots of places. We have this unique community that we have built and continue to build. It validates the marine biomedicine model we have of having a medical school partnering with NOAA and NIST and world-class analytical chemists and biologists."

Into the Lab
Guillette and colleagues have worked extensively for years trying to find out how environmental contaminants and native hormones influence gene expression via steroid receptors – acting as mimics of estrogen, progesterone and testosterone. The question was how to screen chemicals, in this case the petroleum and dispersant chemicals, in a way to avoid testing a wide array of wild animals.

Fortunately, together with Spyropoulos, Kohno and Baatz, they had insights based on their research programs that could contribute a new approach to testing environmental chemicals.

They've developed a technique that can take the estrogen or progesterone receptors from the more than 40 marine animals that have been cloned and put it into a cell with a reporter construct so that when researchers add a chemical, it binds to the receptor, said Guillette.

"That is translated to the reporter, binds to the reporter and turns on a gene and the cell glows, and it does it in a dose-dependent fashion. Now you can say this chemical can be an estrogen or a progesterone or whatever, and determine the dose. It lets us know we now have an active compound to study."

Spyropoulos and Baatz also have been able to harvest lung cells from pygmy sperm whales and make inducible pluripotent stem cells where they took lung cells and "drove them backwards developmentally." Guillette said they'll be able to take aged oil or whatever substance they're studying and test it on cells to see if it changes the developmental process, so instead of stimulating muscle cell growth, the treated cell becomes a fat cell, for example.

"There's a whole world out there we realize of compounds called obesogens. These are chemicals that in the developing embryo instead of stimulating the production of muscle or fiberblast cells, it actually stimulates more fat cells. The chemicals and contaminants in the diet during embryonic development may be programming that body to store more fat."

The Gulf of Mexico research initiative received 629 applications and MUSC was one of 19 chosen. The initiative is helping to build a portfolio of top scientists who are working together.

"The hope is that although the projects are solicited as individual investigator-driven projects, by sharing this information, we are building a community that is interested in finding out what's going on. We can start to get some idea about whether we should be concerned and where we need to do more work."

There are several chemicals that are common, such as BPA found in plastics and tri-butal-tin found near harbors around the world, that have been suggested to have obesogenic activity. Guillette said their BP study can't answer everything, but they know how to be selective in their focus to find those chemicals that do disrupt endocrine cycles.

"We know that obesogens are a critical component and that things like estrogens and androgens are critical for long-term and short-term fertility. We know that glucocorticoids or stress hormones are associated with inflammation and immune function. We can take human glucocorticoid receptors, whale and alligator and fish glucocorticoid, and line them up in different cells and test the chemicals all at the same time. Then we can see if the chemical potentially interacts with the receptor that is associated with stress and immune function, and we can also test if it goes across species."

The Carson Connection
Their work builds on what Rachel Carson believed decades ago, even without the scientific testing methods that researchers have today. If Carson were alive today, he'd like to tell her thank you and that she was right. He's proud to be following in her footsteps.

"If I told you that in a week you're going to get 2,000 chemicals in your body that your grandparents never had in their body, and we have no idea what the health consequences are, and not just in you – it's in your kids too. Would you think that was good?"
The revolution happening is that scientists from critical disciplines are joining forces to change the way this game is played, he said.

"We're coming together to say as biologists, as health professionals, as chemists, we need to start working together. Chemists need to start taking toxicology and health classes, and biologists need to start working with chemists."

It's an immense undertaking and one still surrounded in controversy, but Guillette sees the science winning out.

"We're supposed to be bright people. We're supposed to be leaders in the world in innovation. Let's start innovating. And you know what? There's money in that. There's real money in that because a proprietary chemical is always going to make you more money than something that's 50 years old. If that's your vested interest, that's fine. For me, I just want healthy kids."


Friday, Jan. 11, 2013

The Catalyst Online is published weekly by the MUSC Office of Public Relations for the faculty, employees and students of the Medical University of South Carolina. The Catalyst Online editor, Kim Draughn, can be reached at 792-4107 or by email, Editorial copy can be submitted to The Catalyst Online and to The Catalyst in print by fax, 792-6723, or by email to To place an ad in The Catalyst hardcopy, call Island Publications at 849-1778, ext. 201.