We have had the privilege of interviewing many experts in the fields of genetics, epigenetics, developmental biology, reproductive biology, evolutionary theory, history of medicine, endocrine disruption, neuroscience, toxicology, environmental health, and molecular biology. Each researcher brings new perspective to the multifaceted questions of the history, mechanics and role of germline exposures in genetic change and human development.
Epigenetics: Evolutionary Theory in Transition
Eva Jablonka, PhD, Professor, Cohn Institute for the History and Philosophy of Science and Ideas, Tel Aviv University, Israel
"During [embryogenesis] major changes occur in, for example, DNA methylation and in other aspects of chromatin marking. When things are happening during these periods, they can have long-term repercussions."
Gene-Environment Interaction in the Etiology of Autism Spectrum Disorders
Alycia Halladay, PhD, formerly the Senior Director of Environmental and Clinical Sciences, Autism Speaks
"We literally went through a period of time where it was either genetics or the environment.... [W]hat's been missing in these studies is really an understanding of how the genetics have worked with environmental exposure."
The Role of Epigenetics in Autism Spectrum Disorders
Janine LaSalle, PhD, Professor, Center for Neuroscience, UC Davis
"[P]eople are realizing that genetics alone can't explain autism risk, and that there is compelling evidence for a lot of the genes involved in autism either being epigenetic players themselves or being regulated by epigenetics."
Prenatal Stressors and Epigenetics in the Development of Behavioral Disorders
Tracy Bale, PhD, Professor Neuroscience in Psychiatry, University of Pennsylvania
"Over the last five to ten years, the plasticity has become the novel piece of epigenetics — the fact that there are epigenetic mechanisms that are constantly responding to the environment."
Epigenetic Effects of Prenatal Alcohol Exposure
Ben Laufer, Epigeneticist, Western University, Canada
"I can say with high confidence that molecular aberrations are passed on via the epigenome across generations where they can produce significant differences in neurodevelopment."
Environmental Exposures and Our Dynamic Epigenome
Linda Birnbaum, PhD, Director, National Institute of Environmental Health Sciences
"Air pollution can cause epigenetic changes for example. Hormonally active chemicals like
phthalates and BPA, chemicals like tributyltin, dioxin, PCBs, flame retardants, a wide range of chemicals can cause epigenetic modification."
The Effects of Endocrine Disrupting Chemicals
Carol Kwiatkowski, PhD, Executive Director and Senior Research Associate, The Endocrine Disruption Exchange
"One key characteristic of hormones is that they work at extremely low levels. Very tiny amounts of hormones have effects in the endocrine system. Some hormones work at the level of parts per trillion—this is like one drop of water in 20 Olympic size swimming pools."
Germline Effects of In Utero Exposure to Nicotine
Pradeep Bhide, PhD, Professor of Developmental Neuroscience, Florida State University
“Exposure of the germline to nicotine produces epigenetic changes in the germline... they are permanent, and passed from one generation to the next.”
Ascertaining Germline Risks of Chemical Exposures
Carole Yauk, PhD, and Francesco Marchetti, PhD, Research Scientists, Health Canada, and Adjunct Professors, Carleton University
"We think it’s important to understand whether germ cells respond differently from somatic cells to a chemical exposure because a change in the genome in the germ cell can be transmitted to the next generation and permanently contribute to the population gene pool."
How Epigenetics Influences the Risk of Disease
Susan Murphy, PhD, Associate Professor and Director of the Epigenetics Research Laboratory, Duke University Medical Center
“Probably the most important aspect of germline epigenetic vulnerability is that it is at its highest during pregnancy. This vulnerability occurs within the cells that will form the gametes of the developing child."
Developmental Origins of Disease
Jerry Heindel, PhD, Population Health Branch, National Institute of Environmental Health Sciences
"If it’s a gene that is impacted by the environmental chemical, people put the genetic cause first and view the environmental consideration as a secondary component of the problem. Research might show that a genetic component counts for only 50 or 30 percent of all cases of disease, but we never ask about the remaining 50 or 70 percent."
Persistent Epigenetic Consequences of Critical-Window Exposures
Carlos Guerrero-Bosagna, PhD, Linkoping University, Sweden
"An old criticism of our work is that we used pharmacological doses for our experiments.
It is true, but it was necessary to understand that the epigenetic transgenerational process is
possible.... the next obvious question is exactly that: what are the epigenetic transgenerational effects of these compounds that we purposely take in pharmacological doses?"
Assisted Fertility and Epigenetic Disruption
Marisa Bartolomei, PhD, University of Pennsylvania
"[E]ven though we are more informed about how to test drugs and chemicals, we still do not necessarily know what these compounds are doing to our germline. And what about what happened 50 years ago when we were in utero or young and our germline was developing?"
Public Health Implications of Epigenetics
Andrea Baccarelli, MD, PhD, Harvard University
"A philosophical shift needs to happen in the way we consider biology. And it’s happening now.... At this point we know that the epigenome is a very sensitive biosensor of exposure."
The Developing Genome
David Moore, PhD, Pitzer College
"The bottom line is that even though we hear talk about 'genes' almost constantly these days, the fact remains that molecular biologists have not managed to agree on what a 'gene' even is."
New Discoveries in Genomic Imprinting
Catherine Dulac, PhD, Harvard University
"Normal brain function seems to rely on precise control of gene expression. This has been shown now for a number of brain disorders, such that slight increase or decrease in the expression of key genes lead to widespread dysregulation of normal neural function."
What Glowing Worms Teach Us About Germ Cell Toxicity
Patrick Allard, PhD, UCLA
"It is clear that germ cells have a unique differentiation program and offer a very unique toxicological context.... And there is strong evidence that this early embryonic period represents a critical window of germ cell development."
Non-DNA Mediated Transmission of Behavior Across Generations
Miklos Toth, MD, Cornell Medical Center
"We believe that iterative somatic transmission (through bioactive compounds via the
placenta and breast milk) of behavioral traits is a prominent intergenerational
and multigenerational mechanism."
Chemicals Can Exert Direct Epigenetic Effects on Exposed Fetal Germ Cells
Piroska Szabó, PhD, Van Andel Institute
"I am concerned about harming the exposed germ cells by the chemicals we have tested. I also feel very concerned about potentially harming the germ cells by the many thousands of additional man-made chemicals that humans or wildlife can’t avoid being exposed to."
"DNA is not the sole transmitter of inheritance"
Denis Noble, Oxford University
"What we have learnt in recent years is that much more than DNA is inherited. The germline itself contains RNAs that represent information from the body as a whole, and markings of the genome which also represent information from the body as a whole, and its experience in reacting to the environment."
Pharmaceutical Epigenetic Effects on Fetal Germ Cells
Patrick Western, PhD, Monash Institute, Australia
How Exposures Can Modify the Epigenome
Dana Dolinoy, PhD, Assistant Professor in Environmental Health Sciences, University of Michigan
"If these chemicals impact the epigenome, this can change the programming in the germ line and potentially be transferred across generations. If so, with endocrine disrupting chemicals, you aren’t just impacting the person exposed, you are impacting their children and grandchildren, and possibly their great grandchildren."
Effects of Exposures on Development of Oocytes
Patricia Hunt, PhD, Professor, School of Molecular Biosciences, Washington State University
"[T]here are at least three distinct windows of egg development that appear vulnerable to the effects of BPA; we see effects in adult females exposed prior to ovulation and in fetuses exposed in the womb during two distinct stages of development."
Epigenetics of Human Germline Development
Amander Clark, PhD, Department of Molecular, Cell and Developmental Biology, UCLA
"I've been fascinated to try and unlock the secrets of the germline for many, many years now as I think the genetic and epigenetic health of our germline cells is critical to the health of our children."
Multigenerational Effects of Endocrine-Disrupting Molecules
Emilie Rissman, PhD, Professor of Biochemistry & Molecular Genetics, University of Virginia
"I would stress that our data show that in mice, social interactions, as a class of behaviors, are disrupted by transgenerational exposure to 'human-like' levels of BPA."
How Environmental Factors Can Change the Epigenetics of the Germline
Mirella Meyer-Ficca, PhD, Research Assistant Professor, Utah State University
"[E]xposure during a pregnancy will 'hit' three generations at the same time... the fetuses’ germ cells are already present and get exposed as well. Even more, depending on when exactly during development the exposure occurs, these cells are extremely vulnerable."
Imprinting, Gene Regulation, and Early Development
Randy Jirtle, PhD, University of Wisconsin-Madison, School of Medicine and Public Health
"If these gametic imprint marks are not established correctly in both the egg and the sperm, major developmental and behavioral disorders can occur in the offspring."
Dimensions in Autism Genetics
Wendy Chung, MD, PhD, Columbia University School of Medicine
"Maybe there’s overlap in those pathways among the genetic causes, the epigenetic causes, the environmental causes. I hope to make some sense of this downstream, across the etiologies.”
Connecting Exposures to Epigenetic Effects
Cheryl Walker, PhD, Welch Chair and Director,
Institute of Biosciences & Technology, Texas A&M University
"The developing fetus must undergo all this key programming to sustain the tissue for the rest of the individual’s life, and when endocrine disruptors or other exogenous hormones come on board, they disrupt that program. The epigenetic programming is changed in a way that persists for the entire lifespan of that individual."
Germline Effects of Maternal Smoking: New Study Shows Permanent Impairments to Sperm
Eileen McLaughlin, PhD, University of Newcastle
"Given our past work in females we would be concerned about the polycyclic aromatic hydrocarbons such as benzo[a]pyrene and the activation of the detoxification pathways which are likely to produce very reactive metabolites which could cause direct DNA damage. "
Genomic Imprinting: Regulation of Maternal and Paternal Genes Matter in Brain Development
Christopher Gregg, PhD, University of Utah
"We're figuring out which circuits express imprinted genes and we are learning about critical stages of brain development during which maternally and/or paternally expressed genes function. We are also testing whether perturbations to imprinted genes, due to genetic or environmental effects, can alter specific aspects of brain development and function."
Fetal Origins of Disease: Small Disruptions, Big Effects
Carmen Marsit, PhD, Dartmouth Medical School
"[A]ny changes, any kind of exposures, or any kind of stresses that happen during development ... you can imagine that they can have lifelong impacts because now they're going to change the way that those cells are able to function or behave."
Adverse Multigenerational Effects of Smoking
Virender Rehan, MD, UCLA
"So many things are not obvious unless and until you start looking critically. For example, the nicotine-induced germ cell effects which we see carried on in our rats from generation to generation were surprising to us and were not obvious until we started exploring for these carefully and systematically."
What Causes Genetic Copy Number Variations?
Lucas Argueso, PhD, Colorado State University
"It is known that certain environmental exposures can accelerate the pace of mutation, and this is my main interest, discovering and characterizing agents that may speed up mutagenesis."
A Revolution in Germline Toxicology: PGC-LC's
Toshi Shioda, MD, PhD, Harvard University
"If epigenetic errors occur in the germline genome during the reprogramming process during pregnancy of a woman, her sons or daughters appear normal,
but their germline cells carry a potential bomb."
Prenatal Exposures Oral History Project:
The "Hidden History" of Pregnancy Drugs in the Postwar Era
June Reinisch, PhD, Prenatal Development Project and former director, The Kinsey Institute
"There was a gigantic growth in all kinds of pharmaceuticals after World War II. Since there was this idea of the fetal placental barrier, there was the notion you could treat the mother without interfering with the baby. That went on for much longer than it should have."
Prenatal Exposures Oral History Project:
Postwar Obstetric Practices
Mark Klebanoff, MD, Nationwide Children's Hospital, Ohio
"It gave me a good healthy dose of humility because the between-the-lines message was let's wait another 40 years to find out how many things we do today do more harm than good."