In 2011, much to my shock and horror, I discovered that as a fetus I had been exposed to regular infusions of potent synthetic steroid hormone drugs deployed as part of a then-popular, if ineffective, anti-miscarriage protocol. Knowing a little bit about the chemical mutilation caused by the fake hormone drug DES (diethylstilbestrol), and a bit about epigenetics as well, I immediately began to question whether my acute exposures—specifically, possible errors they may have induced in my nascent eggs—led to the wildly abnormal neurodevelopmental outcomes in two of my children, both of whom have autism, a "genetic" condition completely without precedent in my or my husbands' families.
Shortly after my discovery/hypothesis-conjuring I called my oldest friend to share the news. Her response was immediate: "Josh would have loved this!"
By Josh, she was referring to her late stepfather-in-law, the legendary geneticist and Nobel laureate Joshua Lederberg. Among his many accomplishments, Lederberg was a leader in developing the field of "environmental mutagenesis." According to Brown University sociologist Scott Frickel, the environmental mutagenesis movement grew out of the revelation that new synthetic and toxic chemicals could have lasting consequences for the human genome, amounting to a future "genetic emergency".
Dr. Lederberg was gravely concerned about the possibility the chemical revolution was creating a silent, hidden human genetic emergency that might not be fully realized for decades. As early as 1950, he remarked, "I have the feeling that, in our ignorance, chemical mutagenesis poses a problem of the same magnitude as the indiscriminate use of radiation." (Frickel, Chemical Consequences, p. 51) Five years later, his concerns continued unabated: "more extensive studies are needed to establish, for example, whether the germ cells of man are physiologically insulated against such chemical insults from the environment." (Id.) His colleague James Crow, in "Concern for Environmental Mutagens," summed up their beliefs like this: "The bottom line is human germinal mutation and the translation of this into effects on human welfare. We still have no reliable way to move from DNA damage, however precisely measured, to human well-being n generations from now.... Lowering the mutation rate or preventing its increase is good, even if we don't know how good." (Id. p 135)
Decades before I had an inkling about my prenatal chemical exposures—I was probably about 20 at the time and on a trip with my old friend who was soon to marry into his family—I met Dr. Lederberg in his home on the campus of Rockefeller University, where he served as president. Youth is truly wasted on the young because I can only imagine the lively discussion he and I would have today, three decades later. "Why is DNA particularly vulnerable to artificial steroids and their abnormal molecular structures?" "Why is the FDA refusing to require fetal germline effects of pregnancy drugs, and what can be done to change that?" "What is the interplay between epigenetic alterations and predisposition to mutation?" "What components of cigarette smoke might interfere with DNA repair in fetal germ cells?" And the list could go on and on.
How regrettable that Dr. Lederberg has passed, because it's my impression that the field of genetics today is largely unconcerned with questions like these. Autism genetics, for example, is focused almost exclusively on gene-hunting with scant curiosity about factors that may have actually caused the wide variety of autism-associated errors in the first place. For the past few months I have been actively pushing a variety of autism cohorts to ascertain grandmaternal smoking habits, and while I've had some success I can't help but sense how completely uninterested nearly all leading autism geneticists are in these sort of questions, questions which strike me as obvious and urgent, given what we know about tobacco-induced mutagenesis and the high rates of maternal smoking in the 1950s-70s.
But science has a culture, and presently that culture is divided fairly neatly into scientific silos that tend not to easily intermix. Genetics, mutagenesis, epimutagenesis and chemical/pharmaceutical history tend to be their own worlds. This disconnect may be one of the reasons we're still head-scratching about the colossal surge in autism cases—it seems genetic, but we can't have a "genetic epidemic," right? Or, perhaps, taking a cue from Dr. Lederberg and colleagues, we can. If we're perturbing our germline via novel chemical agents, we most certainly can have a genetic/epigenetic epidemic, what the environmental mutagenesis leaders had called a "genetic emergency" back in the 1960s. It will take a lot more work and creative thinking to probe these questions.
I am now a card-carrying member of the Environmental Mutagenesis and Genomics Society, which Dr. Lederberg co-founded in the 1960s, and now work to further scientific investigation into both genetic and epigenetic consequences of exposures. I hope to continually push for multidisciplinary thinking in autism causation, knowing all the while that "Josh would have loved this."
Jill Escher is the founder of the Escher Fund for Autism, president of Autism Society San Francisco Bay Area, and the mother of two children with nonverbal autism. You can learn more about her story here.
Links to articles and presentations featuring Jill's story and the germline disruption hypothesis of autism:
April 2016, Florida State University Symposium on the Developing Mind keynote: "Out of the Past: Old Exposures, Heritable Effects, and Emerging Concepts for Autism Research." (Slides)
November 2015, Bay Area Autism Consortium Conference, "The Germline Disruption Hypothesis of Autism." (Poster presentation)
September 2015, Environmental Mutagenesis and Genomics Society Conference, "Germline Disruption Hypothesis of Autism, in a Nutshell." (6-minute video)
August 2014, Ancestral Health Symposium: Epigenetics and the Multigenerational Effects of Nutrition, Chemicals and Drugs (40-minute video)
November 2013, University of Illinois School of Pharmacy guest lecture, "Are Grandma's Pregnancy Drugs (from the 1950s, 60s and 70s) Partly to Blame for Today's Autism Epidemic?" (Slides)
September 2013, Pittsburgh Post Gazette: Can Autism Be Triggered in Future Generations?
September 2013, Environmental Mutagenesis and Genomics Society Conference, Epigenetics Special Interest Group keynote, "20th C. Prenatal Pharmaceuticals & Smoking (& More), Fetal Germline Epigenetics, and Today's Autism Epidemic: Any Connections?" (Slides)
August 2013, San Francisco Chronicle: Mother's Quest Could Help Solve Autism Mystery
August 2013, Autism Speaks Blog: A Grandmotherly Clue in One Family's Autism Mystery
July 2013, Environmental Health News: Onslaught of autism: A mom's crusade could help unravel scientific mystery
July 2013, NIH Interagency Autism Coordinating Committee, National Institutes of Health: Autism: Germline Disruption in Personal and Historical Context (15-minute video)
March 2013, presentation at the symposium Environmental Epigenetics: New Frontiers in Autism Research (scroll down for 10-minute video)