I was pleased to be featured on the Autism Speaks blog earlier this month with this post. —JE
Autism’s missing link? Study family history alongside genetics
Can exposures during our own prenatal development affect our children? This mom and autism advocate is funding research to find out
By Jill Escher, founder of the Escher Fund for Autism. Jill has two children with autism and is a longtime supporter and collaborator with Autism Speaks.
The dominant idea in autism research today is that the causes of autism are largely genetic. As a result, funding for autism research has emphasized hunting around DNA for clues.
I agree this is essential. However, to my mind, it’s also incomplete. It's not enough to draw blood and sequence our genes. We should put equal effort into investigating family histories.
Why our histories? To be blunt, our histories are not just about us, they’re also about our sperm and eggs – our gametes – the raw material that give rise to our children. Remember learning in biology class that “a girl is born with all her eggs?” Our gamete-producing cells, in both males and females, didn’t develop in a vacuum: They tangoed with environmental exposures, starting in our mothers’ wombs.
Looking beyond DNA
You probably know of obvious exposures that can affect genes. Examples include carcinogens such as tobacco smoke and mutagens such as X-rays. Both can directly damage DNA. In addition, emerging research shows that some drugs and other chemicals (including so-called “endocrine disruptors”) can modify how our genes operate without altering their underlying DNA code. This is the science of epigenetics, the study of mechanisms that control how genes turn on and off at the proper time and place.
Our gametes are vulnerable to a variety of environmental influences, and their vulnerability can set the stage for disorders and diseases.
Let me offer a hypothetical illustration about how this might work. Say a medical treatment for children involved repeated X-rays of the abdomen. That radiation could cause genetic errors in the children’s egg- or sperm-progenitor cells. As a result, their offspring, born decades later and conceived of those cells, might have higher rates of certain genetic disorders.
Now, I will argue that other, perhaps less obvious, gene-environment interactions may be tinkering with our genes. Take my family history as an example. My husband and I have two autistic children, ages 17 and 10. We have no family history of autism or mental disorders. The conceptions, pregnancies and deliveries were entirely normal with no notable risk factors. The kids are robustly healthy, and genetic tests have failed to show anything amiss. But their brains clearly did not wire up in the typical fashion. They remain severely challenged and nonverbal to this day. Are their genes alone to blame, or is there something more?
I believe that autism research is entering a new era
where we no longer look at genes and environment in isolation.
Our family stories will be instrumental in breaking new ground
and solving some of autism's deepest mysteries.
Exploring my own prenatal exposures
Several years ago, I discovered some troubling news about my own history. I obtained detailed medical records showing that during my mother’s pregnancy, I was prenatally exposed to heavy and continuous doses of powerful synthetic steroid hormone drugs. At that time, some doctors used many of these drugs (these were endocrine disruptors, or hormone mimics) to prevent miscarriage – though it turns out they were ineffective, and in many cases, profoundly damaging.
Now you might be thinking, what a weird idea that medications that my mother took during pregnancy with me in 1965 could cause developmental problems in my children decades later.
It might make sense if you consider that my early egg cells were already present when I was developing in my mother’s womb. Could the fake hormones given to my mother have disrupted the normal process of reprogramming in my budding egg cells? If so, molecular glitches in my eggs might manifest as dysregulations of development decades later, after my children were conceived and then missed their early milestones.
Some researchers have termed this the "time bomb" hypothesis, because of the proposed delayed effect of gamete, or germline, exposures that occurred decades before.
In recent years, I’ve met many autism parents with similar in utero exposure histories – some involving pharmaceuticals, tobacco or illegal drugs. I’ve grown particularly concerned about the fetal germline impacts of all the heavy pregnancy smoking of the 1950s through 1970s. Though pregnancy drugs and smoking were rampant in those decades, few people have asked about the health and development consequences to the generation exposed as gametes. There are plausible connections to dysregulation of neurodevelopment.
However, a plausible connection is not enough. It's just a place to start. Now we must move forward with serious research investigating the possibility of such gene-environment interactions. To kick-start this area of research, I support pilot projects through a grant program, in addition to my education and advocacy work.
Collaborating with Autism Speaks
I've also found a wonderful collaborator in Autism Speaks. Already, Autism Speaks and the Escher Fund for Autism have sponsored, with the UC Davis MIND Institute, the first scientific symposium on Environmental Epigenetics in Autism.
Now Autism Speaks, the Escher Fund and the Autism Science Foundation are sponsoring an ongoing, free webinar series probing epigenetics and gene-environment interactions in autism. Autism Speaks also funds a number of innovative research projects exploring the epigenetics of autism.
I believe that autism research is entering a new era where we no longer look at genes and environment in isolation. Our family stories will be instrumental in breaking new ground and solving some of autism's deepest mysteries.
To learn more, also see:
“What is epigenetics and what does it have to do with autism,” in the Autism Speaks “Got Questions?” advice column.
Environmental Epigenetics Webinars co-sponsored by Autism Speaks, Autism Science Foundation and Escher Fund for Autism
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Jill Escher, Escher Fund for Autism, is a California-based science philanthropist and mother of two children with severe autism, focused on the question of how environmentally induced germline disruptions may be contributing to today's epidemics of neurodevelopmental impairment. You can read about her discovery of her intensive prenatal exposure to synthetic hormone drugs here. Jill is also president of Autism Society San Francisco Bay Area.