"We must be much better caretakers of our genetic legacy"

From the SF Chronicle yesterday. A shorter version of the story that appeared in Environmental Health News earlier this month.

--Jill Escher

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http://www.sfchronicle.com/health/article/Mother-s-quest-could-help-solve-autism-mystery-4682498.php

Mother's quest could help solve autism mystery

Jane Kay

8:23 AM

Katy Raddatz, Katy Raddatz/Environmental Health

Two of Jill Escher's three children are autistic, despite the low chances.

Jill Escher, a dark-haired dynamo of smarts and stamina, was gently stopping her son, Jonny, 14, from ripping up the mail. He had just emptied spice bottles on the table to make finger paints.
Upstairs, Escher's daughter, Sophie, 7, was sending out incomprehensible cries. It could mean that Sophie had opened a box of crayons, eaten some and rubbed the rest into the carpet, or smeared a tube of toothpaste on the mirror. And while Escher tried to calm Sophie, Jonny could be tossing his iPad over the fence, tearing all the ivories off the piano, chewing the furniture or wandering out into traffic.

For Escher, the anguish of autism is doubled. Both Jonny and Sophie have been diagnosed with autism, the fast-growing category of neurological disease afflicting 1 in every 88 U.S. children. The Escher children's intellectual development is stalled at an early preschool level, and they need constant care and protection.

For years, Escher and her husband worried about what could have gone wrong. Why would two of their three children wind up autistic, defying the odds? Was it their genes? Their environment? The San Jose couple tried to hunt down any health problems in their lineage but found none. According to the Centers for Disease Control and Prevention, parents who have a child with autism have only a 2 to 18 percent chance of having a second autistic child.

New studies appear with regularity, suggesting causes but offering no definitive answers for Escher.
"To be perfectly honest, I had given up trying to find out. I felt I would die never knowing what happened to my children. No one could tell me," Escher said.

An idea is sparked

 

But three years ago, Jill Escher had an epiphany, one that now subsumes her waking hours and nighttime dreams. After prodding her mother for clues from her past, Escher discovered some hidden history: Her mother had sought help conceiving at a fertility clinic. As she grew in her mother's womb, Escher was bombarded with synthetic hormones and other drugs.

Now Escher's dogged quest to unravel why this happened to her children has drawn the attention of scientists and may ultimately lead to a greater understanding of how prescription drugs, and perhaps chemicals in the environment, may secretly and subtly harm the health of generations to come.

"The autism explosion has been with us for more than two decades, and we have little to show about what's causing it," Escher said. "We have many hundreds of thousands of functionally disabled people who didn't exist before, and we have our heads in the sand."

Katy Raddatz, Katy Raddatz/Environmental Health

Jill Escher, who has a law degree, educated herself enough about autism to discuss research with experts.

Scientists know that some chemicals can alter developing embryos and fetuses, which can lead to disease later in life.

But in recent years, they've learned that the damage doesn't necessarily stop there. Something a pregnant woman is exposed to may alter not just her children but also her grandchildren and perhaps all subsequent generations.

This is how the "germ line" hypothesis works: Cells in what is called a germ line form eggs in the female fetus and precursors to sperm in the male fetus. The germ line establishes an unbroken link from generation to generation. But when a pregnant woman is exposed to chemicals, the germ line may be altered. That would mean that eggs developing in the fetus, the future third generation, could be changed, leading to abnormalities or disease.

Pregnancy drug

 

The power of pharmaceuticals to do just that came to light with a synthetic estrogen called DES, or diethylstilbestrol, which was prescribed to up to 10 million pregnant women from 1938 to 1971 in an effort to prevent miscarriage and premature birth. DES daughters, exposed in the womb, are at an increased risk for cancer of the vagina and cervix and other reproductive disorders. Startling scientists, DES granddaughters turned up with an increased incidence of reproductive abnormalities.
These findings were profound: A single exposure in the womb could induce defects that could be transmitted to the next two generations.

Now health experts probing autism wonder: Could this be a clue? Could a pregnant woman's exposure to something alter the brains of her grandchildren?

"Twenty years ago, the view in the field was that autism was totally a genetic disorder, and if you could figure out which genes were involved, then you would understand the cause of autism. Now we've gotten to the point where we're saying environmental factors have just as much influence as genetics," said neuroscientist David Amaral, research director at UC Davis Mind Institute.
With no scientific training, Escher, 47, who has a law degree, has educated herself enough to discuss new research with Amaral and other autism experts.

"I was listening to a podcast," Escher said, "and a health guru explained that a pregnant woman's nutrition affects not only her fetus but also her grandchildren because of exposure of the germ cells. I heard her say, 'A girl is born with all her eggs.' "

She was stunned. "Something's happened to my eggs," she thought.

Generational link

 

Millions and millions of women who are now grandmothers took heavy doses of drugs during their pregnancies in the '50s and '60s. Escher wondered: Could the fertility, nausea and miscarriage drugs heavily prescribed in the past decades alter the fetus and lead to lasting, transgenerational abnormalities such as autism?

One of the first scientists she contacted was Michael Skinner at Washington State University. Skinner laid out the shift in thinking that is setting off waves of disagreement among geneticists. Scientists long believed that only alterations in the DNA sequence could be passed on to subsequent generations. Now there is evidence that the way in which normal genes are expressed, or turned on and off, can be passed on, too. This is called epigenetic inheritance.

Many diseases have increased faster than can be explained from normal genetic mechanisms. The epigenetic phenomenon could be a reason.

"If environmental factors influence gene expression, the risk of someone having autism could increase," Amaral said.

One large study, published earlier this year, reported that children of women who took valproate, prescribed for epilepsy and psychiatric disorders, had a significantly higher risk of autism spectrum disorders than other children.

"There are many pieces of information learned from more than a decade of study that need to be connected before any conclusion can be made about autism," said Andrea Gore, professor of pharmacology and toxicology at the University of Texas at Austin.

"We think most behavioral disorders are a combination of genetic predisposition, natural differences in reproductive hormones and differences in environmental exposures."

Taking action

 

Two months ago, Escher petitioned the FDA seeking revocation of Diclegis, approved this year as the first antinausea drug for pregnant women, until it is tested for effects on the fetus' developing germ cells. Her cause is supported by some scientists.

A representative of Duchesnay Inc. said the Canadian pharmaceutical company worked with the Food and Drug Administration in evaluating Diclegis. The drug has not shown an increased risk to the fetus during pregnancy, according to an e-mailed statement.

FDA spokeswoman Andrea Fischer said, "the science of epigenetics is new. ... As with all emerging science, the FDA will review data and consider its potential for impact on regulatory decisions." She said the agency is reviewing Escher's petition.

As for her own inspiration, Escher said, "I love my kids. But I don't want this to happen to anyone else. It's too hard. It's too damaging.

"We have unwittingly experienced this mass disruption in evolution. It has to stop. We have to be much better caretakers of our genetic legacy."

Jane Kay is a writer for Environmental Health News. For a longer version of this story, go to http://bit.ly/15fjVMq.