Onslaught of autism: A mom's crusade could help unravel scientific mystery

Lance Neilson/flickr 

 

Jane Kay
Environmental Health News

July 16, 2013

SAN JOSE, Calif. – 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, her 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.

Katy Raddatz

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 one in every 88 U.S. children. The Escher children's intellectual development is stalled at an early pre-school level, and they need constant care and protection.

For years, Escher and her husband, Christopher, 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? Their food? The couple tried to hunt down any health problems in their lineage but found none. A glass of wine while pregnant? Paint fumes? Pollution from freeways?

New studies appear with regularity, suggesting causes but offering no definitive answers.

“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.

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.”

From generation to generation

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 possibly even subsequent generations.

National Institutes of Health

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. Also, the disrupted programming in how genes are turned on and off – the very genes that instruct cell growth and function – may be passed on to more descendants.

“The autism explosion has been with us for more than two decades, and we have little to show about what's causing it. We have many hundreds of thousands of functionally disabled people who didn't exist before, and we have our heads in the sand.” Jill Escher  The power of pharmaceuticals to do just that came to light with a synthetic estrogen that harmed at least two generations of offspring of women who took it. DES, or diethylstilbestrol, was prescribed to up to 10 million pregnant women in the United States and the United Kingdom 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 a rare form of cancer of the vagina and cervix and other reproductive disorders, and the sons have increased risk for some reproductive problems. Startling scientists, DES granddaughters turned up with an increased incidence of urinary and genital malformations, irregular menstrual cycles and other abnormalities.

These findings were profound: A single exposure of a pregnant woman seemed to induce defects in her fetus's eggs, triggering health effects in the next generation.

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?

A personal quest

When Escher’s first child, Evan, was born in 1997, he met his developmental markers. Two years later came Jonathan. “He was really colicky, and always seemed to be in some pain that we couldn't soothe. He would sit in the backyard and pick up rocks and dirt,” she said.

She saw the ominous signs: no eye contact, no babbling as a baby. The Eschers took him for an assessment. As soon as the doctor walked into the waiting room, he suspected autism.

Jill Escher saw the ominous signs in her son Jonny: no eye contact, no babbling as a baby. As soon as a doctor walked into the waiting room, he suspected autism. Then when Sophie was born seven years later, she showed similar signs.“Jonny is a brick. Nothing permeates his skull. He was just impervious to what we were trying to teach him. He was an affectionate little boy and remains so today,” Escher said.

Then when Sophie was born seven years after Jonathan, she showed similar signs. She didn't play or make eye contact. Her diagnosis came soon after. Genetic testing revealed no known abnormalities in either child, and no clinician could think of any reason for two children with such severe disabilities.

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.

In 2000 and 2002, one in every 150 U.S. children was diagnosed with autism spectrum disorders, which affect the brain’s normal development of social and communication skills. But the rate climbed to one in 88 in 2008, according to the CDC. Many experts believe the rise is due to a combination of a real increase in prevalence plus improved diagnoses.

“We don't know why the numbers are increasing, and we don't know which portions of the brain are affected when a person has autism,” said neuroscientist David Amaral, research director at the University of California, Davis, MIND Institute.

“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,” he said.

“The majority of brain disease has been shown not to be genetically based, and autism is likely environmentally induced during some period of development.” –Michael Skinner, Washington State UniversityWith no scientific training, Escher, 47, has educated herself enough to discuss new research with Amaral and other autism experts. She has a law degree from the University of California, Berkeley, and five years' experience as a clerk in the U.S. District Court in San Jose. Five years ago, Escher and her husband founded a small family fund that first financed school recreational activities for autistic children, then research into its causes.

To her horror, she learned that researchers had discovered an autism cluster in West Los Angeles, where she grew up. In her search for answers, Escher came across a Tel Aviv University study linking in vitro fertilization with increased risk of autism.

“That's when it hit me that I might have been a fertility kid,” she said. She remembered a scrap of information tucked away. At 13, the cover of Time magazine featured a test tube to illustrate creating a baby with the aid of science. Someone – she thinks it was her dad – said to her, “You were just like that baby. You were a miracle child. You were wanted very badly.” She wasn’t a test tube baby, but she wondered if her mother had taken fertility drugs.

Escher called her mother, and asked. “They gave me a whole bunch of stuff. I don't know what it was,” her mother said.

At Escher's request, her mother called her former obstetrician. Four pages of records, stored on microfilm, were sent to Escher. Scrawled over the pages was a list of synthetic hormone drugs that her mother took. Over and over, she saw steroid hormones: Deluteval (a progestin with estradiol) and prednisolone. Escher learned that her mother had gone to a West Los Angeles fertility clinic run by Dr. Edward Tyler, who had prescribed Pergonol and Clomid to induce ovulation to help her conceive. And it was Tyler who had prescribed a continuing regimen of hormones and steroids, including weekly injections, as a way to prevent miscarriage during the pregnancy.

Washington State University

Escher asked some autism researchers about the fertility drugs, but got no encouragement, so she set the records aside.

But when the sister of a friend who had been exposed to DES in the womb died of breast cancer, she realized that the effects of some drugs could last for generations. “DES was a real eye opener in terms of transgenerational effects of prenatal exposure to drugs,” she said.

“I was listening to a podcast, 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.

Searching the epigenome for answers

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?

So far, no one has looked, although one ambitious study is about to be launched in Europe.

“Right now research looks at environment and it looks at genetics. But it doesn't look at the environmental effects on the germ line. These are critical questions. So far we're silent on them,” Escher said.

Science is very compartmentalized, she said.

“We already have all the pieces. We just need to put them in order. But you don't have one person stringing it all together,” she said.

Escher is trying to be the one to do that.

One of the first scientists she contacted was Michael Skinner, a professor in the School of Molecular Biosciences at Washington State University.

Skinner laid out the shift in thinking that is setting off waves of disagreement among geneticists. For more than a century, scientists believed that only alterations in the DNA sequence could be passed on to subsequent generations. Now they are considering a change in that thinking: The way in which normal genes are expressed, or turned on and off, may be passed on, too. An abnormal exposure to a pregnant woman – a toxicant or smoking, for instance – might change the genetic switching that controls the development of a fetus. These alterations then may be passed on to multiple generations.

This is called epigenetic inheritance.

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