When the Beckman Institute opened 25 years ago, neurodevelopmental toxicology, which examines the effects of environmental toxicants on neurodevelopment and behavior, was in its infancy. Susan Schantz, a professor of comparative biosciences and Beckman researcher in the NeuroTech Group, believes that within a relatively short period of time, the field has made some very important advances.
One, according to Schantz, resulted from the arrival of epigenetics, the study of heritable changes in gene activity that are not caused by changes in the DNA sequence.
“We’ve always known that early developmental exposures have long-lasting effects,” said Schantz, “but what’s the mechanism for that? Epigenetics explains how you can have early exposures that permanently alter gene expression and lead to health problems later on, or that cause a non-genomic change that is expressed later in life when there’s some other kind of triggering factor.”
Another important contribution, says Schantz, is the knowledge that the environment can contribute to neurodevelopmental and neurodegenerative diseases, such as attention deficit hyperactivity disorder (ADHD), autism, and Parkinson’s disease.
“I think in the past we were focused on understanding the genetic causes of these diseases,” said Schantz. “Now there is a focus on gene-environment interaction, which means people get a disease because they have a susceptible genome and are exposed to particular environmental factors.”
Schantz is the director of the new Illinois Children’s Environmental Health and Disease Prevention Center at the Beckman Institute.
The center, funded by a five-year, $8 million grant from the Environmental Protection Agency and the National Institute of Environmental Health Sciences, is an extension of a formative center, which was established in 2010 to study exposure to bisphenol A (BPA) and phthalates.
BPA is used in shatterproof plastics, dental fillings, electronics, and the linings of metal food and drink containers. Studies have found BPA in human urine, blood, breast milk, and the amniotic fluid of pregnant women. Phthalates, which are used in plastics, cosmetics, building materials, wrappers, textiles, toys, and in the coating of some time-release medications, have been shown to cause birth defects in rodents given high exposure.
The center is interested in both prenatal and adolescent exposures to these chemicals, and how they affect reproductive system and nervous system development and behavior. The center hosts four closely linked research projects: two human cohort studies and two laboratory animal studies, as well as an outreach component.
A pilot birth cohort study conducted during the formative stage initially looked at 157 mother-infant pairs. The current study, called the Illinois Kids Development Study (I-KIDS), expands the smaller study considerably. Researchers are recruiting 600 women during their first trimester of pregnancy, so that they can follow at least 500 additional children to examine the effects of BPA, phthalates, and other endocrine-disrupting chemicals, including the antibacterial agent triclosan, on infant and child development. The first baby of the new cohort was born in June 2014, and children from the original cohort, who are now nearly three-and-a-half years old, are still being followed.
In an interdisciplinary approach to research, this study is incorporating techniques commonly used in other disciplines for evaluation and data collection.
“We had pretty novel ideas about how we were going to assess infants, looking at cognitive function beginning at birth, using approaches that aren’t typically used in epidemiology,” said Schantz. “We take methods typically used in developmental psychology to study cognitive development and are revising the data collection approach so that we can use these approaches in the context of a large epidemiological research study.”
Another study in the center examines adolescents who were part of a similar birth cohort. Parallel to these studies in humans, research with laboratory animals is assessing both reproductive development and function, and neurodevelopment and function, relative to the animals’ exposure to the same chemicals.
Both the human and animal studies will assess whether obesity—either maternal obesity in the case of prenatal exposures or child obesity in the case of adolescent exposures— interacts with chemical exposure to increase health risks for the child.
A “research translation” program aims to build a public conversation about the scientific consensus on the everyday consumer chemicals that may influence child health.
Schantz focuses her research mainly on chemicals in consumer products, but she has also looked at exposures to polychlorinated biphenyls (PCBs). Although all of the chemicals she studies can have detrimental effects on human health and neurodevelopment, there are many differences in their prevalence and their effects.
“BPA is very different from PCBs,” said Schantz. “It’s not stable, it’s metabolized very readily in the body. PCBs bioaccumulate in your body—you store them in your body fat. But BPA has a very short half-life: you take it in, you break it down, and it’s gone. It doesn’t build up. But the problem is that it’s very widely used in many consumer products, so everybody’s exposed every day to BPA. One of the biggest problems with BPA is that it affects development, which is problematic because that’s when the brain and organs are forming.”
Additional studies have shown that early exposure to PCBs causes hearing loss due to functional changes in the outer hair cells of the cochlea and that these changes are linked to audiogenic seizures in rats. Schantz works with Dan Llano, Beckman full-time faculty member in the NeuroTech Group, on laboratory animal studies that look at how PCBs affect development of the auditory system.
Another collaborative Beckman project is developing a new method for eye tracking, which is one method used to evaluate the cognitive function of infants. Most eye tracking devices use infrared cameras, which are costly and require special expertise to set up and run. Schantz is working with the Image Formation and Processing Group, led by Thomas Huang, to develop new visible light eye tracking procedures for infants.
“We’re trying to see if we can develop ways we can accurately track an infant’s eye movements with just a computer webcam and a laptop computer. We’re working closely with (Beckman affiliate faculty member) Dan Hyde on that. I don’t think I would really have ever gotten into this if someone hadn’t said, ‘You should really talk to these computer vision people. They might be able to help you.’ That’s the intellectual environment that Beckman provides.”
Schantz is excited about the possibilities that the National Children’s Study offers for studies in neurodevelopmental toxicology.
The multi-year research study will examine the effects of environmental influences on the health and development of 100,000 children across the United States, following them from before birth until age 21. The goal is to improve the health and well-being of children.
“The plan is to look at all sorts of environmental exposures, but also other things like social factors and other environmental factors and how these things affect the growth and development of children,” said Schantz. “In particular for some rare diseases, like certain types of childhood cancers, you really need a large sample size to understand them.”
Research done at the Illinois center could help to inform the national study.
“The children’s centers are conducting smaller studies around the country on various types of exposures and using different approaches,” said Schantz. “But we’ve learned a lot about what works, what doesn’t work, and factors that are important to consider, so there’s been an effort over time to use lessons we’ve learned in the Children’s Centers to help inform the National Children’s Study.”