The Mother of All FDA Fails

The FDA has never required drug safety assessment for fetal germline impact, even though FDA staff understand that gestational exposures can adversely affect developing germ cells. We must end this catastrophic omission, while also granting all Americans access to their own prenatal medical records.

Moving the Shop

Thanks to everyone who has followed this blog.  In order to create a more robust (and more scientific and less ranty) repository of information about germline disruption, I have sponsored a new website,

It will feature expert interviews, scientific information, and more.  Given the amount of work I have on my plate doubt I will have time to keep up this blog, but please check in with the new site from time to time.  Thanks!

Jill Escher

Prenatal Drug Use in the 60s, Two Snapshots

How pervasive was pregnancy drug use in the 1960s?  We can look at two cohorts, the CHDS (Child Health and Development Study) and the Collaborative Perinatal Project to get a sense of this vast history.  The top chart shows CHDS drug use throughout pregnancy, and the bottom two refer to drug CHDS and CPP drug use in roughly the first half of pregnancy.

Use of anti-nausea drugs, sedatives, hormones, painkillers and amphetamines were all common.  Which of these abnormal exposures entered the womb and fetal tissue? All of them.  Which of these affected fetal development? Most of them, though sometimes very subtly.  Which of them affected fetal germline?  Well, we hope to find out.

On the Almost Two-Year Anniversary of the Germline Disruption Hypothesis of Autism

Nearly two years ago I sent the following email to a large group of researchers and autism leaders (including Tom Insel at NIMH, Autism Speaks, and noted scientists from UCLA to Texas to Hopkins) outlining for the first time the germline disruption hypothesis of autism.

So much has happened since that time to confirm my suspicions — meeting many other autism parents with circa 1960s prenatal drug exposures just like mine, studies of multigenerational effects of endocrine disruptors and hypomethylation in animal models, findings of various multigenerational effects in human cohort studies, recognition of epigenetic involvement in some neurodevelopmental impairments, findings regarding de novo alterations in germline in autism, increasing recognition of gene-environment interaction in autism, to name a few — and as we head into the holiday season let us hope for a 2014 filled with long-overdue public awareness about this most urgent issue.

Jill Escher

Epigenetic Transgenerational Inheritance: How Old Pharmaceuticals May Be Contributing to the Autism Epidemic Today

Summary Document, January 20, 2012


That the increasing rate of ASDs stems in part from epigenetic disturbance of fetal germ cells caused by in-utero exposures to various pharmaceuticals, including synthetic steroid hormones, used in obstetric practice from roughly the 1950s to 1980s.  In other words, that gestating women given certain pharmaceutical drugs in roughly the first half of pregnancy (likely window is weeks 6-18 of gestation) are more likely to have neurologically impaired grandchildren, through the action of epigenomic alterations of fetal germ cells.


From the 1950s through 1970s, and even before, it was common in obstetric practice to prescribe various pharmaceuticals to pregnant women, even in the first trimester.  The drugs included, among other things, hormone-like compounds, barbiturates, and morning-sickness medications.

In the post-war period chemists began synthesizing various progesterone-like compounds. Based on theory that these compounds could help prevent miscarriage or preterm birth, some obstetricians and early fertility clinics began administering synthetic progestins to pregnant women deemed to have at-risk pregnancies. Commonly, the patients had suffered prior miscarriages or had complications such as bleeding. Use of the compounds was relatively rare in the 1950s, but increased through the 1960s and 70s, particularly in certain locales with a large upper-middle class clientele who could afford the then-expensive fertility treatments, including west Los Angeles and New Jersey, the sites of cohort studies by Dr. June Reinisch.

There was no standard practice for use of these compounds, according to Reinisch, it was more of an art than a science.  Some physicians administered multiple hormones, some used hormones early in pregnancy, some later.  There was no standard dosing.

Little thought was given to the impact of the various drugs, including the progestins, on the exposed fetus.  The progestins were chemically similar to progesterone, except for a small “tail” or “radical” hanging off the end of the molecule. They were not, like DES (diethylstilbestrol), very chemically different from the natural counterparts.  While the idea of impact on fetal germ cells did come up, it was thought at the time that the germ cells would be protected from exogenous chemical exposures.

Dr. Reinisch and a few others did perform research on first-generation impact of prenatal exposure to synthetic steroid hormones.  Impacts on brain development were found, though subtle compared to a neurodevelopmental disorder like autism.  The impacts were primarily on personality traits.  See, eg, Reinisch and Karow,“Prenatal exposure to synthetic progestins and estrogens: Effects on human development.” and “Prenatal exposure to synthetic progestins increases potential for aggression in humans,”

Some of the pharmaceuticals used

According to Prenatal Exposure to Synthetic Progestins and Estrogens: Effects on Human Development, Archives of Sexual Behavior, Vol 6, No. 4, 1977, p. 267, the most common synthetic steroid hormones used in pregnancies deemed at-risk appear to have been (progestins) Colprosterone, Delalutin, Deluteval, Norlutin Acetate, Provera, Provest, and (additional estrogens) Stilbestrol.  Full list from that study:

Broxorone (Squibb)
Colprosterone (e)
Deladroxate 110 (Squibb)
Deladroxate 130 (Squibb)
Deladroxate 150 (Squibb)
Delalutin 142 (Squibb)
Delaxadrone (Squibb)
Deluteval (b) (Squibb)
Depo-Provera (Upjohn)
MK665(c) (Merck) ethymerone
19NET, Norlutin (Syntex)
Norlutin Acetate (Parke Davis)
Norethynodrel (b) (Searle)
Pranone (Schering)
Provera (Upjohn)
Provest (b) (Upjohn)
RS1280 (c, e) (progestogen)
SC4641 (c) (Searle) 19 NET
SC4642 (c) (Searle) norethynodrel
SC9022 (c) (Searle) methylnortestosterone
SC10230 (c,g) (Searle)
SC11800 (c) (Searle) ethyndiol
1 142.53 (e) aqueous progesterone
Additional estrogens (d)
Allyl Estranol (Organon)
Amestrogen (Squibb)
Delestrogen (Squibb)
Estrone (a)
Hexestrol (e)
Mestranol (e)
Stilbestrol (e)
Other drugs
Thyroid (Armour)
Cytomel (Smith, Klein& French)
Methergine (Sandoz)
Prednisone (McKesson)
Proloid (Wamer-Chilcott)
Sterane (Pfizer)
Synthroid (Flint)

a Many mothers received more than one drug.
b Compounds that have estrogens included.
C Experimental compounds.
d Not including estrogen found in combination with progestin.
e Company not identified.
f Number of pregnancies in which medication was administered (omitted in this list, see article)
g 21-Fluoro-17-hydr oxy-6-methylpregna-4,6-diene-
3,20-dione acetate.

Other pharmaceuticals, such as the barbiturates and morning sickness medications, were also prevalent, however I do not have a list of those medications at this time.

The “Hidden History”

Reinisch calls the past use of these hormone-like pharmaceuticals, as well as the barbiturates and morning sickness drugs, the “hidden” history for several reasons:
--The records have largely been destroyed
--The women who received the medications often did not know what they were getting
--The women have largely forgotten taking the medications
--The exposed children were never told of their exposure
--The practice was very little studied, and has been forgotten by contemporary researchers and medical practitioners

Case Study

By the end of 1964 a well-to-do 27 year-old mother of one son in Los Angeles had suffered two miscarriages and badly wanted another child.  She sought treatment at a pioneering private fertility clinic in west Los Angeles which was associated with UCLA.  She conceived after being given clomiphene and Pergonal to induce ovulation.  Through at least the first two trimesters, she was then given regular doses of a synthetic progestin, Deluteval 2x, manufactured by Squibb, for the ostensible prevention of miscarriage (these compounds were never actually proven to promote gestation).  It appears Prednisone was also administered at some point.  She delivered a healthy baby girl in September 1965. 

This child now has three children of her own (“grandchildren”), two of whom have markedly abnormal neurological development (label used is autism).  All genetic tests have been negative, including tests for cnv’s and microdeletions.  All pregnancies and deliveries were normal, and Apgar scores were high.  The families of the grandchildren have no history of neurological problems or mental illness.  There were no unusual exposures during the pregnancies.  In spite of the very evident neurological dysfunction, the children are robustly healthy and normal-looking.

The child born in 1965 also has a younger brother, born in 1968.  He, too, was exposed to exogenous synthetic steroid hormones.  He is the father of two children, one of whom has a mysterious neurological disorder that is similar to NF1, though apparently not genetic in origin.  The older brother, unexposed to any hormones, has two normal children.

Several other autism parents (both mothers and fathers) are also aware of their own in-utero exposures to synthetic steroid hormones:  symptoms reported in the offspring include Aspergers, autism, sensory processing disorder, and learning disorders.  Many of these second-generation offspring also have no apparent, or very mild, symptoms.

However, the vast majority of the parents who were exposed have no idea about their prenatal histories--nearly all records have long ago been destroyed, and it appears to have been uncommon for a mother to think of the medication as worth mentioning to her offspring.

Background Research

It has been postulated that common pharmaceuticals could have epigenetic side-effects that appear only years or decades after the exposure.  See, eg, Szyf, M “Epigenetic side-effects of common pharmaceuticals: A potential new field in medicine and pharmacology.”

Researchers such as Michael Skinner, Andrea Gore, Moshe Szyf, and Joseph Nadeau have looked into transgenerational epigenetic impact of chemical exposures and have found early evidence for the phenomenon.  See, for example, Nadeau “Transgenerational genetic effects on phenotypic variation and disease risk,”, Skinner et al, “Endocrine Disruptor Vinclozolin Induced Epigenetic Transgenerational Adult-Onset Disease,”, and Skinner, “Role of Epigenetics in Developmental Biology and Transgenerational Inheritance,”

New studies on endocrine disruptors, some yet unpublished, point to differing epigenetic impacts on the F2 and F3 generations, likely due to impact on developing germ cells. (Interviews with Szyf and Gore, December 2011, and Skinner, January 2012.)

There is broad agreement, even among traditional geneticists, that it is biochemically plausible that the synthetic hormones, or their metabolites, or other prenatal pharmaceuticals, could have had a deleterious impact on germ cell reprogramming. Various theories were espoused, including altered methylation patterns and impact on histone tails during reprogramming. It is agreed that at a minimum, synthetic steroid hormones would cross the placenta, enter fetal tissues, and likely bind to receptors in ways that vary from natural, endogenous steroids. The reasons for epigenetic alterations of germ cells to lead specifically to a phenotype of abnormal neurodevelopment are unknown.

Professor Skinner summarizes the core biochemical issue in his article cited above, “Role of Epigenetics in Developmental Biology and Transgenerational Inheritance” as follows (emphasis added):

[T]he basic mechanism of epigenetic transgenerational inheritance involves the actions of an environmental factor (e.g., chemical or nutrition) during germ line remethylation at gonadal sex determination to permanently alter the germ line epigenome (Anway et al., 2005; Guerrero-Bosagna C et al., 2010; Skinner et al., 2010) to then transmit this altered germ line epigenome to subsequent generations (Anway et al., 2005; Anway et al., 2006a,b; Anway and Skinner, 2008; Guerrero-Bosagna C et al., 2010; Skinner et al., 2010). As the embryonic stem cell epigenome is altered due to this germ line transmission, all cell populations and tissues will have an altered epigenome and corresponding transcriptome (Anway et al., 2008; Skinner et al., 2010). The germ line generated by the next generation will also have this altered epigenome and transmit it to the subsequent generation (Guerrero-Bosagna C et al., 2010; Skinner et al., 2010). Exposure to the endocrine disruptors at other times of development do not appear to have the capacity to permanently alter the germ line epigenome (Anway et al., 2005; Anway and Skinner, 2008; Skinner et al., 2010). Of course, the vast majority of exposures will alter the somatic cells at critical periods of development to modify later cellular development and potential adult onset disease, Figure 1, but this does not have the capacity to become transgenerational as the germ line is not involved (Skinner et al., 2010). Epigenetic transgenerational inheritance through a permanently altered epigenome of the germ line has the capacity to have a dramatic influence on developmental biology, as well as other areas of biology such as evolution.

In the event the base-line epigenome is altered, then the cascade of epigenetic and genetic steps during development will be altered and a modified differentiated or developmental state achieved, Figure 1. Therefore, epigenetic transgenerational inheritance has a dramatic effect on the developmental biology of all cells and tissues derived from the germ line transmitting this modified baseline epigenome. Although not all cell types or tissues will develop a disease state, those tissues that have a sufficiently altered transcriptome will have a greater susceptibility to develop disease (Skinner et al., 2010). As all development and differentiation processes involve a cascade of epigenetic and genetic steps, alteration of the baseline epigenome, similar to alteration in the genetic baseline, will have the capacity to promote abnormal development which may lead to disease later in life. For this reason, environmentally induced epigenetic transgenerational inheritance through the germ line will have a significant impact on developmental biology. This mechanism and consideration of the cascade of integrated epigenetic and genetic events during development, Figure 1, will be an important factor in disease etiology not previously considered (Skinner et al., 2010).”

What this hypothesis might explain

It goes without saying that there are many roads to the various phenotypes we lump together under the label of autism.  Among them: genetic disorders, prenatal and perinatal complications, prematurity and multiple birth, prenatal exposure to certain pathogens or chemicals, and seizure disorders.  However, it is worth noting that the pharmaceutical/epigenetic hypothesis is consistent with a great many research findings, as follows:

--Abnormally high rates of autism in west Los Angeles (the site of early, aggressive fertility and prenatal treatments beginning in the 50s)
--Abnormally high rates of autism in New Jersey (same)
--Rising rates of autism diagnoses after about 1990 (the time when the early crop of grandchildren of the growing number of women treated in the 1960s were entering their preschool years)
--Findings of certain epigenetic signatures in autism brains
--The lack of evidence for a genetic root of most cases of ASD
--Findings implicating very early neurological development in ASDs
--Certain demographic patterns, eg, why certain religious or ethnic populations that had little access to or interest in prenatal care have lower autism rates
--The vast heterogeneity of the ASD syndrome

Some of the researchers with whom I spoke agreed that pharmaceuticals could be playing a role, but that other low-level environmental exposures such as to plastics, endocrine disruptors, stress and hydrocarbons could also be contributing.  I feel the need for an editorial comment here:  I cannot fathom how ubiquitous and low-level exposures like those can possibly compare to the sometimes huge direct doses of potent (though forgotten) pharmaceuticals injected directly into our mothers during the first half of pregnancy.  The study of the pharmaceutical impacts appears to be of much greater urgency.

Early Initiatives

Various early initiatives have been proposed:

Epidemiology.  There is broad agreement that epidemiological work should be done.  There exist at least four distinct cohorts of individuals known to have been exposed to exogenous hormones in utero.  It would be important to do prospective studies (starting with obstetric records of the grandmothers, and working downward), and not retrospective studies (starting with autistic kids, and working up the family tree).  This is due to the absence of reliable information of past pharmaceutical use of the grandmothers. To do meaningful epidemiological work, one would need not only the basic knowledge of “exposure” but also the identities of the drugs used, the dosages, and the timing.

--Denmark (Dr. Reinisch is looking into the possibility of a second-generation study on this cohort, which is part of the Prenatal Development Project at Kinsey)
--Finland (Dr. Brown is looking into the possibility of a second-generation study on this cohort, which had been identified by E Hemminki as part of a study into the fertility rates in this cohort)
--Los Angeles (Dr. Reinisch’s detailed files on individuals exposed in utero to synthetic steroid hormones, in the 1960s and 70s, still exist, in storage at the Kinsey Institute)
--New Jersey (same as above)

Quite possibly, with some sleuthing, cohorts exposed in utero to various pharmaceuticals could be found within initiatives at Kaiser and at Johns Hopkins as well.

Broader epidemiological work, looking at data from several countries at once, was also suggested.  However, the integrity of the data regarding the F1 (grandmother) pharmaceutical use is in question.

History.  A few researchers suggested doing a basic history of past obstetric pharmaceutical use around the world, since it is so poorly understood, and attempting to make connections to the development of various diseases, including ASDs, increasing in prevalence today.

Animal models.  A great many researchers suggested three-generation animal modeling.  This way, different compounds and different timing of exposure could be tested for resulting changes in behavior, brain morphology, and epigenetic changes.

Case studies.  A few researchers suggested doing direct epigenetic studies on affected families. However, others cautioned that such studies would be difficult owing to the complexity involved in studying the epigenome.

In summary

Long-forgotten pharmaceutical use may be playing a significant role in the autism epidemic today.  If this is the case, there is urgent work to be done in terms of prevention, family planning, changing fertility and obstetric medical practice, reducing pharmaceutical use by women of childbearing age by shifting emphasis to natural treatments of chronic conditions, ensuring all prenatal medical records remain available and never discarded, and possibly, finding targeted therapies for the many disabled individuals suffering from artificially altered epigenomes.  Therefore, expediting research into this hypothesis is critical.

Germline Disruption Hypothesis of Autism in the News

I've had quite a few requests for places people can go for news about the Germline Disruption Hypothesis of Autism.  Here are some:

July 2013, Environmental Health News: Onslaught of autism: A mom's crusade could help unravel scientific mystery

July 2013, NIH Interagency Autism Coordinating Committee: Autism: Germline Disruption in Personal and Historical Context, (15-minute video)

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,

September 2013, Pittsburgh Post Gazette: Can Autism Be Triggered in Future Generations?

Also, many scientific presentations relating to the topic of epigenetics of germline disruption are archived at

Letter to Ob/Gyn Leader Urging Clinicians to Protect Fetal Germ Cells from Pharmaceutical Exposure

Jill Escher
Escher Fund for Autism

Jeanne Conry, MD
American Congress of Obstetricians and Gynecologists
PO Box 70620
Washington, DC 20024-9998

October 14, 2013

Re: Urgent request to revise clinical practices to protect fetal germ cells from pharmaceutical exposure

Dear Dr. Conry:

I am writing with a most unusual request, as I realize it is not altogether common for a mother to advance a wholesale paradigm shift in the practice of obstetrics and gynecology, maternal-fetal medicine, and reproductive endocrinology. But in this case, the stakes are so high, the consequences so catastrophic, and the blind spot so glaring, I feel I have no choice but to speak up, and loudly.

My appeal is both common-sense and grounded in science: that clinicians working with pregnant women take into consideration risks of pharmaceutical exposures to fetal germ cells, the delicate precursor cells to egg and sperm, before administering or recommending any drug before or during pregnancy. These all-important cells will confer the genetic and epigenetic material from which the following generation (the patients’ grandchildren) will spring. But if these cells, which undergo rapid and environmentally vulnerable synthesis in utero, are genetically or epigenetically(fn) adulterated by exogenous exposures, abnormal development of the grandoffspring may result.

It goes without saying that pregnancy exposure affects three generations simultaneously: the mother, her baby, and the baby’s germ cells. The medical profession has a laudable recent history of concern for the myriad proximal fetal effects of in utero chemical and drug exposure, but for reasons that are difficult to comprehend, thus far such concern has not extended to the fetal proto-gametes, which are arguably the most critical cells within the fetal body.

Perhaps these third-generation tissues have not garnered the profession’s attention due to a faulty assumption that, short of outright mutagenesis of protein-coding sections of the genome, human germ cells, and the process of early oogenesis and spermatogenesis, are somehow immune to environmental influence.  But we know this is not true: during certain windows of susceptibility, particularly the period of epigenetic germline reprogramming that occurs in weeks 6-18, abnormal exposures can exert strong influence on the molecular integrity of the germline. Aside from epimutagenesis, exposures can destabilize protein-coding or non-protein coding regions of the genome, damage DNA repair mechanisms, or provoke atypical transposon activity.  Of particular relevance is research demonstrating marked germline effects of endocrine-disrupting substances that disrupt or augment hormone actions, which is not surprising in light of the density of hormone receptors populating the membranes of these precious cells.

Germline development is a highly conserved, but dynamic and environmentally responsive process chaperoned by hormones, and choreographed with tremendous molecular precision over billions of years of evolution.  Small perturbations in epigenetic marking can, for example, lead to imprinting disorders such as Prader-Willi or Angelman’s syndromes.  Defects in epigenetic mechanisms are also implicated in Rett Syndrome, for example. Studies in animal models demonstrate that gestational chemicals can wreak multigenerational havoc, resulting in numerous pathologies, including behavioral abnormalities, defects in sexual development and fertility, metabolic disruptions, and cancer. In human epidemiology, we have observed third-generation effects of diethystilbestrol and nutritional stress.

My interest in this area stems from personal experience.  I was born in 1965 after having been exposed in utero to a cocktail of ob/gyn-administered chemicals, including ovulation-inducing drugs and seven months of various synthetic steroid hormones (progestins, glucocorticoids, and estrogens) that were fairly commonly used in the 1960s and intended at the time for the prevention of miscarriage. I know of my drug exposures in detail owing to the miracle of having recently obtained my prenatal medical records from a Los Angeles ob/gyn office where my mother had been a patient. Almost all such records have been destroyed; few of my generation know of their prenatal drug exposures in any detail.

Ordinarily, such old records would be of little interest, but the concern runs not so much to my somatic cells, though my body and brain were certainly permanently altered by those early exposures. The concern runs to my ova, as my children, who are genetically normal and came from normal, healthy pregnancies with no risk factors, are idiopathically autistic.

After connecting the dots between my endocrine-disrupting prenatal exposures, likely epigenetic perturbations during early oogenesis, studies showing autism risk genes “hotspots,” abnormal methylation in post-mortem autism brains, and my children’s mysteriously impaired neurodevelopment, I found family after family after family with the same story.  In the course of my surveys of autism families, I found that about 30 percent of autistic children were born of parents who suffered substantial prenatal pharmaceutical drug exposures during the heyday of the prenatal pharmaceutical craze of the 1950s, 60s, and 70s.

Those drug exposures include progestins, synthetic estrogens, glucocorticoids, sedatives (such as phenobarbital), anti-nausea medications, and psychoactive medications.  The prevailing false belief in those decades regarding the protective “placental barrier,” combined with the explosion of new and heavily marketed synthetic drugs, led to the unprecedented mass medicating of pregnant women in that era.  This meant, of course, that three generations were medicated at once.  
Only the most vulnerable of those generations was not the mother or the fetus, but the relatively unadorned and unprotected germline; and the molecular-level birth defects to that generation would lay dormant for several decades.  It is not a coincidence that the autism epidemic began in the 1980s, or that autism has been shown to be highly “heritable” among siblings, even without any autism in the family ancestry, or that a significant subset of autism appears to involve de novo changes in gene function involving hypermutable long genes on the genome.

Distressingly, women’s use of medications before and during pregnancy seems to have abated little.  Hormone drugs remain widely and intensively used in fertility practice, maternal antidepressant and ADHD drug use is rampant, anti-nausea drugs have drifted back into fashion, and, given the growing incidence of diabetes, PCOS, digestive problems, thyroid disease and hypertension, the use of many other drugs, many of them endocrine disruptors, has also climbed.

In light of widespread gestational pharmaceutical use and the risks of perpetuating the horror of chemically induced fetal germline disruption, combined with your organization’s mission to promote patients’ and the public health, I ask your organization to please consider the following:

Publish this letter in the ACOG Newsletter and other publications, both paper and online.

Support my petition to the FDA. The Escher Fund for Autism has petitioned the FDA to consider potential impacts of prenatal pharmaceuticals on fetal germ cells, and to advise consumers of potential germline risks.  In an unfathomable lapse in judgment, scientific understanding, and diligence, the FDA has never before considered fetal germline impacts of pharmaceutical drugs.  Please find my petition, and submit comments online, by searching “Escher Fund for Autism FDA Petition.”

Warn all pregnant and pre-pregnant patients of potential dangers to fetal germline.
Systematically inform women who are pregnant or considering having a child of exposure risks to fetal germline posed by not just prescription pharmaceuticals, but also OTC drugs, smoking, drinking, recreational drugs, pesticides, endocrine disruptors, and poor nutrition. Of greatest concern, however, are the acute drug and pharmaceutical exposures.

Support full disclosure to exposed individuals.  Support a national policy requiring that all children born of medicated pregnancies, including all children resulting from fertility treatments, be advised in writing of their specific exposures, including timing, doses and identity of all drugs  and manipulations used, and that these F1 offspring be counseled regarding the heightened risk of bearing F2 children with developmental impairments.

Support a policy requiring retention of all prenatal medical records indefinitely.
Because prenatal exposures can have lifelong health consequences, in addition to germline consequences, we must ensure that all prenatal medical records are kept in electronic media that can be accessed by all three generations directly exposed to the drugs.

Advocate for biologically conservative, and evolutionarily compatible, clinical practice.
  Support clinical practice that refrains from prescribing any drug, particularly any drug with hormonal or endocrine-disrupting properties, unless absolutely necessary. For example, advocate for cessation of use of discretionary glucocorticoids, which have already been demonstrated to have adverse germ cell impacts, and minimize use of progesterone and progestins, particularly during weeks 6-18 of gestation when germline synthesis is at its height. Minimize, and attempt to eliminate, use of antidepressant drugs, which have endocrine-disrupting properties. And take extreme care to minimize periconceptional exposures, as that period presents another window of susceptibility to epigenetic derangement.

Advocate for clinical practice that emphasizes restoration of natural fertility and endogenous hormonal normalcy. School your professionals in the principles of evolutionary medicine and ancestral health so they can expand their clinical toolbox to include reproduction-compatible interventions well beyond genotoxic approaches pharmaceutical companies are pitching.  For example, focus on supporting women’s transitions to highly nutritious, low-inflammation diets free of sugar, grains, or processed food, but rich in healthy fats and dietary cholesterol, and dense with micronutrients and natural (not synthetic) folate and other methyl donors. Reduction of endocrine-disrupting compounds, whether natural or synthetic, is also essential.

While we may be many decades away from fully understanding every mechanism of molecular genetics and epigenetics affected by every prenatal drug and chemical exposure, is beyond debate that xenobiotic in utero exposures can cause errors in germ cells.  When in 1961 we perceived that thalidomide was causing horrific birth defects, no one said, “Let’s first ascertain the physiological mechanism before we issue a prudent warning.” Synthetic adulteration of germline, however inadvertent it may have been, represents the greatest medical disaster in history, having spawned a torrent of incapacitating disability among those born within the last three decades, and its catastrophic multigenerational effects will echo through the centuries. We can, however, stem further damage.

Thank you for your  prompt attention to this matter. Please feel free to contact me any time, I am at your disposal.

Very truly yours,


Jill Escher

ACOG board members

With similar letters to:
Fertility and Sterility, editorial board members
American Society for Reproductive Medicine, board members
Society for Maternal-Fetal Medicine, board members
Society for Reproductive Endocrinology, board members
American Medical Association
Rachel Turow, JD, Food and Drug Administration
Margaret Hamburg, MD, Commissioner of the Food and Drug Administration

(fn)  In the event of unfamiliarity with epigenomics, epigenetic mechanisms refer to the many layers of molecular mechanisms that affect gene expression and regulate genome dynamics.  Two of the major categories of epigenetic marks are DNA methylation and histone modifications.

The Hidden History that Helped Trigger the Autism Epidemic, a Slide Show

I was invited to speak at two conferences recently, the Environmental Mutagenesis and Genomics Society annual meeting, a confab of top scientists who study how environmental exposures affect our genes, and the annual Morgan Autism Center Conference, an event aimed primarily at parents and teachers.

I have received a number of requests to post my slides online, so I'll post the Morgan Center presentation here and try to get to the Mutagenesis presentation soon.  My main point at Morgan Center was that autism parents can (and must!) be much more active participants in autism research, particularly in causation hypothesis hunting.  Given what we now know about the vital importance of ancestral exposures during windows of germline and fetal vulnerability, and that tens of millions of us had been prenatally exposed to powerfully genotoxic drugs (I was exposed in utero to synthetic steroid hormone drugs in excess of the equivalent of 20,000 birth control pills!), our stories are untapped goldmines of information that I believe will help solve many mysteries of the horrible autism epidemic. WE JUST NEED TO CONNECT SOME PRETTY DARN OBVIOUS DOTS, PEOPLE!