Latest Expert Interviews: Fetal Germ Cell Vulnerability, Non-Genetic Transmission of Traits, and the "Hidden History" of Prenatal Drugs
We are pleased to announce the addition of five fascinating new expert interviews at GermlineExposures.org.
Toshi Shioda, MD, PhD, Harvard University:
A Revolution in Germline Toxicology: Primordial Germ Cell-Like Cells (PGC-LCs)
One of the barriers to understanding germline exposure risk is the lack of effective and reliable models for mechanistic studies. Dr. Shioda’s lab has taken advantage of cutting edge tools from stem cell biology and deep sequencing technology to develop germ cell models on which new toxicological tests could be run.
"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."
Piroska Szabó, PhD, Van Andel Institute:
Chemicals Can Exert Direct Epigenetic Effects on Exposed Fetal Germ Cells
Dr. Szabó's recent paper in Genome Biology reported that endocrine disruptors affected the global transcription and DNA methylation state of exposed fetal mouse germ cells, but these aberrations were not passed on to the germ cells of the subsequent generation.
"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."
Miklos Toth, PhD, Cornell Medical Center:
Non-DNA Mediated Transmission of Behavior Across Generations
Maternal factors during sensitive periods of development produce persistent effects in the offspring, including effects on brain development and behavior. Dr. Toth's latest paper looks beyond fetal effects to successive generations, looking at altered methylation and gene expression in genes whose functions can be linked to behavioral traits, and ultimately, changes in neuronal function and behavior in generations of mice.
"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."
June Reinisch, PhD, Prenatal Development Project, and former director, The Kinsey Institute:
The "Hidden History" of Pregnancy Drugs in the Postwar Era
Prenatal Exposures Oral History Project
Dr. Reinisch is renowned for her pioneering investigations of adverse impacts of various post-war pregnancy drugs, including once-common synthetic steroid hormones and barbiturates, on fetal development. In the 1970s Jill Escher, who had been exposed in utero to large quantities of synthetic steroid hormones, was one of her study subjects.
"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."
Mark Klebanoff, MD, MPH, University of Ohio:
Postwar Obstetric Practices
Prenatal Exposures Oral History Project
Dr. Klebanoff has examined a variety of outcomes in cohorts of pregnancies from the post-war decades, during which some myth-driven obstetric practices were the norm.
"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."
See all 35 expert interviews:
[This post was written by my friend, a DES victim named Marcia Love. It was written for her blog IWantAnApology.com. While I was not a DES daughter, I was exposed in utero to heavy amounts of other synthetic steroid hormones, and I identify with her plight and outrage at the lack of accountability in the medical and regulatory systems regarding this violently toxic pregnancy drug that was given recklessly to millions of gestating women. I'm proud to say I am now sponsoring a study on grandchild (germline) effects of DES on development of those offspring of exposed gametes. -Jill Escher]
They Made Us Freaks And Gave Us Cancer!
The True Story Of The Largest Disaster In Pharmaceutical History
by Marcia Love
This page is about the drug Diethylstilbestrol.
When you think about the largest or greatest drug disaster most people think of Thalidomide which was certainly a devastating catastrophe. The heartbreaking pictures of those born without limbs or those with deformed limbs can never be forgotten by those who have seen them.
In terms of the number of people affected Diethylstilbestrol was far worse. Th CDC estimates that over ten million people were exposed.
There are a few very profound differences between the two drugs.
First, the physical defects from Thalidomide were very apparent and immediate. A baby born with no limbs draws attention. One born with a 40x increased risk of cancer 20 years down the road not so much.
Next we have the fact that Thalidomide was not distributed worldwide so the number of people exposed was far less. The number of people exposed to Thalidomide is in the tens of thousands.
Then there is the fact that Thalidomide is still being sold and in fact many studies have for instance shown it to be effective in the treatment of multiple myeloma, especially when used with other drugs.
And of course Thalidomide was never sold in the U.S.
For these reasons every scientist on the planet and most lay men as well know about Thalidomide but very few know about Diethylstilbestrol.
Know that the pharmaceutical industry here in America operates the same way the tobacco companies did foryears. Deny responsibility, Deny your product kills and pay shills to promote your product in the face of increasing evidence which says that it indeed kills.
In 2012 Gruenenthal Group (The company which sold Thalidomide) to mothers and their children for the tragedy.
No such apology has ever been offered for Diethylstilbestrol.
In 2010 then senators John Kerry and Scott Brown sent a letter asking for an apology from the FDA. The response they got was something like “we are making sure that doesn’t happen again.”
They never got their apology…
Diethylstilbestrol was discovered in England at Oxford University in 1938 by Sir Charles Dodds.
It was found to have have estrogen like effects and was marketed as a cheap synthetic replacement for estrogen. The supposed premise that it was sold on was that since it behaved like estrogen it could be used as a cheap synthetic estrogen.
As it turns out Diethylstilbestrol is not a synthetic estrogen but an endocrine disruptor.
Dodds warned of intersex and cancerous outcomes and the FDA initially denied approval of the drug.
This did not stop the pharmaceutical companies from aggressively campaigning to get the drug approved. The reason? It was a free drug that anyone could manufacture and sell. English lay at the time forbade money to be made on anything discovered with public funds.
The drug companies pooled their resources and formed what was known as the Small Committee, hiring former Eli Lilly CEO Don Carlos Hines to represent them.
Soon there was an article in the Readers Digest stating that a new wonder drug for treating post-menopausal symptoms was available and was just awaiting the approval of the FDA.
Such articles asked readers to send letters to their congressmen and even the president. The aggressive campaign worked and by 1940 the FDA had approved it for use in treating gonorrheal vaginitis, menopausal symptoms, atrophic vaginitis and lactation suppression. The gonorrheal vaginitis indication was removed when penicillin was discovered.
At the behest of their pharmaceutical representatives doctors also began prescribing Diethylstilbestrol off label for the purpose of preventing miscarriages. As with the other four approved indications no proof was ever provided as to the efficacy of the drug for this purpose.
Scientific method was not widely used at this point in history because the FDA did not yet require it even though it was standard practice as early as the late 1930’s. So the MD was easily convinced by the affable drug rep to prescribe it for his at risk patients without any proof that it actually worked.
Off label prescription of Diethylstilbestrol for preventing miscarriage ended in 1947 when the FDA approved it for that use after years of pressure from the pharmaceutical companies. They convinced doctors and patients alike to write letters attesting to the safety and effectiveness of the drug.
Then came George and Olive Smith two “researchers” from Harvard who began advocating for an increasing regimen ending at 125 mg/day during the final month of pregnancy. At the time Eli Lilly was selling it in doses of .1,.5 and 5 mg. The most outrageous thing is that there was absolutely no proof of efficacy of these large doses because the scientific method had yet to be employed on the drug!
So then Bristol-Myers Squibb sought and and was granted permission to market and sell Diethylstilbestrol in doses of 25 mg and 100 mg.
As a fetus develops it’s hormonal needs vary by the micro-second and it is impossible for anyone to know what those exact needs are. DES is a powerful endocrine disruptor and introducing it into the womb at random times leads to arbitrary results.
Some women ended up with a T-Shaped uterus, some did not. Some sons became transgender, some did not. There are commonalities in mothers, sons and daughters however.
Finally in 1951 a double blind study was conducted at the University of Chicago and Diethylstilbestrol was proven to have to no effect on the prevention of miscarriages.
This fact did not slow down sales however. Coming from someone who was born in 1956 and exposed to the Smith & Smith regimen you can imagine how heartbreaking that fact is.
The person I was meant to be was never born and my body was permanently altered before I was born for no reason other than profit.
Study after study proved that Diethylstilbestrol did absolutely nothing to prevent miscarriages but yet the FDA still allowed it to be sold.
By the late 1960’s six of the seven leading textbooks on Obstetrics and Gynecology said Diethylstilbestrol had no value in preventing miscarriages but it wasn’t until 1971 when the New England Journal of Medicine published a study which found an astounding link between vaginal clear cell adenocarcinoma and in utero exposure to Diethylstilbestrol in women and young girls. Prior to this that type of cancer was only found in older women and even then only rarely.
Even after it was proven to cause cancer the FDA only removed prevention of miscarriage as in indication for Diethylstilbestrol use and added pregnancy as a contraindication for Diethylstilbestrol use.
The FDA never banned DES outright and other indications were allowed to stand but as evidence mounted the FDA started taking more action against it and in 1975 ordered 25mg and 100mg tablets withdrawn from the market.
In 1978 the FDA removed postpartum lactation suppression from their approved indications and by the 1990’s the only approved indications were for advanced breast cancer in postmenopausal women and for the treatment of advanced prostate cancer.
Finally in 1997 the last U.S. manufacturer Eli Lilly stopped making and marketing Diethylstilbestrol.
For 60 years Diethylstilbestrol was prescribed for made up reasons without any scientific data whatsoever to warrant it’s prescription. If it wasn’t so heartbreaking it might be laughable some of the reasons it was prescribed.
Starting in the 1950’s and continuing through the 1970’s Diethylstilbestrol was prescribed for “excessive height” in prepubescent girls, particularly in Australia.
The CDC estimates that 10 million people were exposed between 1938 and 1971 the vast majority for the prevention of miscarriage ruse. That means 5 million DES mothers gave birth to 2.5 million DES sons and 2.5 million DES daughters.
From the CDC’s website:
“More than 30 years of research have confirmed that health risks are associated with DES exposure. However, not all exposed persons will experience the following DES-related health problems.
In addition to causing cancer Diethylstilbestrol is a known teratogen, that is it is capable of causing physical malformations to those exposed in utero.
DES exposed daughters have a higher risk of reproductive tract abnormalities including epithelial cell changes known as vaginal adenosis, an increased cervical transformation zone and uterine abnormalities such as a T-shaped uterus.
In 2005 Dr Scott Kerlin published the results of an on-line survey of DES sons.
Out of 500 surveyed 150 men reported gender identity issues. Looking at the math:
150/500 x 2.5 million = 750,000 male to female transexuals were artificially created by the pharmaceutical industry.
Estimates of the natural occurrence of transexualism was somewhere between 1 in 5,000 to 1 in 70,000 depending on who you believe. Sill noting compared to the 3 in 10 you get when administering DES into the womb.
I am a DES son and there is virtually no help out there for me. I have a microphallus, ovaries, intermittent gender dysphoria and a whole lot more.
I am demanding an apology from the FDA, Eli Lilly and Bristol-Meyers Squibb and Harvard University.
Because of their blind pursuit of profit, ignoring all scientific proof of the harm their products do to developing fetuses and refusing to take responsibility I and millions of others have suffered greatly and have led miserable lives.
Their greed has caused me life-long pain and humiliation and ensured I would never find the happiness our constitution allows us to pursue.
It is time to fight back…
Letter to FDA's Center for Tobacco Products Regarding Study of Tobacco Smoking Impacts on Germ Cells
Escher Fund for Autism
Director, Center for Tobacco Products
FDA Document Control Center
10903 New Hampshire Avenue
Building 71, Room G335
Silver Spring, MD 20993-0002
October 17, 2016
Re: Center for Tobacco Products Efforts to Address Tobacco-Induced Human Germ Cell Damage
Dear Mr. Zeller,
I am a science philanthropist primarily concerned about adverse mutagenic and epimutagenic effects of various drugs, pharmaceuticals and tobacco on the human germline.
Based on my admittedly partial review of CTP activities, it appears that the CTP limits its concern for adverse outcomes of tobacco exposure to the somatic level. While questions of somatic pathology such as lung cancer, addiction, and heart disease are clearly of utmost importance in safeguarding public health, they also miss an entire dimension of risk.
Owing to its various toxic components, tobacco smoke has been shown to cause adverse impacts on germ cells. It has been shown to induce mutation in germ cells in human studies and animal models, as well as somatic mosaicism in animal models. At least one study points to transgenerational neurodevelopmental effects of nicotine, most likely via epigenetic mechanisms. The mutagenic and epimutagenic properties of tobacco smoke are now well known.
It is therefore surprising that the FDA’s CTP does not seem to include human germ cells, both male (sperm and precursors) and female (eggs and precursors), as a potential endpoint for tobacco toxicity. If in fact the high pregnancy smoking rates of the past decades increased risk for germline mutation and/or epimutation, developmental abnormalities in resulting offspring may be significant, and may include neurodevelopmental disorders such as autism and ADHD.
I am writing to inquire about what you think could be done at the CTP to ensure the FDA expeditiously addresses tobacco-induced risks to germ cells, particularly the highly vulnerable early germ cells that lie within fetuses. Health Canada, for example, has an admirable program on the gametic genetic toxicology of tobacco. What can we do to ensure a vigorous response here in the United States at the FDA as well?
Thank you for your consideration.
Very truly yours,
Escher Fund for Autism
My name is Jill Escher. I'm a science philanthropist who kickstarts pioneering research projects investigating the generational toxicity of certain potent exposures, including DES, tobacco and other drugs. While I'm not a DES daughter, I was exposed to a multitude of other synthetic steroid hormones in utero as part of a then-popular, if ineffective, "anti-miscarriage" practice. You can read my story here. You can see my science website at GermlineExposures.org.
Based on human, animal, and in vitro studies, as well as family interviews, I hypothesize that DES, along with several other toxic substances, can damage the genomic information in early fetal-stage gametes. For a variety of reasons, the early gamete is probably the single most vulnerable stage of the human lifecycle. Damage during that phase, which could be genetic or epigenetic in nature, can manifest as abnormal development in the subsequent offspring.
For example, I hypothesize that the intensive synthetic steroid hormone drug regimen to which I was subjected as a fetus subtly deranged the molecular programming of my early eggs. This derangement I believe resulted in the starkly abnormal neurodevelopment — autism — of my children. I have met many other families with the same story.
I am pleased to announce that I am funding the world's first research study into the grandchild effects of DES (3d gen), looking specifically at neurodevelopment and behavioral impacts. This work will be done in collaboration with Harvard University, based on the Nurses' Health Study II. If you can support this work, please contact us.
Thank you for your support! If you have any questions, please do not hesitate to reach me at: firstname.lastname@example.org
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.