Phila. becomes hotbed of autism research

Shortly after their 18-month-old daughter was diagnosed with autism in 2009, Beth and John Yocum enrolled her in a language-learning study at Children's Hospital of Philadelphia. She got a comprehensive evaluation - a full day of examining, questioning, playing - from a team of experts, all of it free.

"They were amazing," Beth said. "We got a lot of very good advice from the doctors about where Amanda stood development-wise from their tests, and what types of therapies we should seek to help her progress."

Now the Yocums have a new baby, and the entire family is part of another study, this one run nationally by Drexel University. It is the largest effort to find environmental triggers of autism.

Five years ago, Philadelphia was not on the map when it came to researching one of the most mysterious and expensive childhood medical conditions of our time. Now it is among the top cities in the nation, with expertise in nearly all the key fields - genetics, environmental exposure, brain imaging, behavioral interventions - that are critical for finding causes and developing treatments.

Most of the local talent is at the Center for Autism Research at Children's Hospital, which in less than four years has grown into a powerhouse with more than 100 researchers and staff running two dozen studies.

Drexel is jumping in with a much smaller but ambitious Autism Public Health Research Institute, which is poised to lead in some other areas, beginning with environmental exposure. The long-neglected field has suddenly become a priority as evidence builds that genes alone do not explain the disorder.

The goal is to figure out what flips the genetic switch that puts some infants on a path to autism. Only then can scientists begin to understand how the brain changes and what can prevent it, discover treatments, and devise cost-effective ways to teach hundreds of thousands of schoolchildren.

"It takes a community to do this," said Nancy Minshew, a professor of psychiatry and neurology at the University of Pittsburgh.

Autism - the most serious of the Autism Spectrum Disorders, with Asperger's syndrome among the higher-functioning forms - is a developmental disability defined by a set of psychological impairments that typically show up by 18 months.

"Autism is like a snowflake," said Robert Schultz, director of the center at Children's. Its core attributes - mainly an inability to engage in normal social interaction - are enough to define it. But the severity, symptoms, and timing of each case are different. So huge research samples are needed to discover what they have in common.

Current therapies - mostly teaching through association to change behaviors - are extremely time-consuming and work for some but not others. There is no cure.

The Centers for Disease Control and Prevention now estimates that roughly one of every 70 boys and one of 300 girls is on the autism spectrum, as much as triple the estimate from just two decades ago. Many scientists believe that much if not all of the striking rise is due to changing definitions, more awareness, and better diagnosis.

Meanwhile, assumptions about what causes autism have changed radically. A half-century ago, the origin was believed to be psychiatric: Autistic children were seen as withdrawing from emotionally frigid parents.

Recognition that children with an autistic twin were more likely than others to develop the disorder shifted attention to genes. In the 1980s and '90s, scientists turned en masse to the hot new field of genetics. Several genes were linked to autism - the first discovered in 2009 by teams led by Hakon Hakonarson of Children's - but none explained the majority of cases.

Nor did genetics account for skyrocketing rates. "Genes don't change that quickly," said Clara Lajonchere, a researcher at the University of Southern California. "So there has to be something else going on that is influencing, perhaps, genetic expression."

Lajonchere was part of a team that studied 54 pairs of identical twins and 138 pairs of fraternal twins to see how much difference genes made in the odds of developing autism spectrum disorder. Their calculations, published in July in the Archives of General Psychiatry: Shared genes accounted for 38 percent; shared environment, 58 percent.

What scientists refer to as "environment" is basically anything not genetic. The Drexel-led research is trying to narrow that down.

In Beth and John Yocum's living room in Malvern, where their autistic toddler, Amanda, often plays, a field worker clad in scrubs and booties vacuumed straight lines along the floor, tables, chairs, and toys, bagging minute amounts of dust for the lab.

In the kitchen, with 12-week-old Samantha bouncing on her knee, the girls' mother answered an interviewer's questions: What kind of soaps do you use? Yard tools? Toothpaste? Computers? Two pages of questions concerned pesticides for the dog.

Siblings of autistic children are far more likely than others to be diagnosed with the disorder; a Pediatrics study published in August put the risk as high as one in five. So the investigators will be following the development of up to 1,200 babies, while tracking all the soaps, lotions, pesticides, tools, air, and machinery that surround them, beginning in the womb.

At age 3, when most children who will develop autism have been diagnosed, researchers will analyze reams of environmental data looking for what was different for the siblings who became autistic. The oldest of 200 siblings enrolled so far is not yet 2, said Craig J. Newschaffer, principal investigator for the EARLI (Early Autism Risk Longitudinal Investigation) study.

Newschaffer was recruited to Drexel's School of Public Health, where he chairs the Department of Epidemiology and Biostatistics, in 2006. He launched the $17 million EARLI study three years later and had talked with incoming university president John A. Fry, who has an autistic nephew, about what more Drexel might do.

In April, Fry dropped a surprise into his inaugural address: Drexel was creating an institute to examine autism from a public health perspective; Newschaffer would direct it. With a projected $20 million to be raised over the next five years, the institute is expected to add several researchers to a handful already spread around campus. They will focus on autism in the broader population.

"Our approach is to identify patterns in a community that can be acted upon," said Igor Burstyn, an epidemiologist. Burstyn has examined hypothetical links between autism and mothers' smoking (none found), and lack of oxygen at birth (a possible link in boys). Now he will be able to devote more time to the field.

Other faculty will evaluate services for young adults. With rising numbers of people on the autism spectrum enrolling in college, for example, campuses across the United States are struggling to help them.

With no evidence of what works, every program is different. Drexel researchers could try to identify the "active ingredients" of effective support programs, Newschaffer said, using measurable outcomes such as landing a job after graduation to gauge success.

Newschaffer's own work on environmental risk factors is the only part of the institute that is fully up and running. He directs the study at four locations nationwide, including Philadelphia, where the dust- and lotion-gathering at families' homes is handled by Drexel while clinical evaluations of the developing babies are done at Children's Hospital.

And if Drexel can identify environmental triggers, "we can take it further," said Schultz, who was recruited from Yale in 2007 to develop Children's center. "We can test how they interact with different kinds of genes. We can test whether new treatments can be effective."

While Drexel will focus on niches not filled elsewhere, the center across the Schuylkill does just about everything. Schultz's brain-imaging research led to a series of computer games that use facial cues to improve the social skills of children on the autism spectrum. A new study that began last week will continue the games and add oxytocin, a natural hormone that has been found to improve social learning.

Another researcher, David Mandell, in June completed what is believed to be the largest study of teaching techniques in real urban classrooms, a setting that can be quite different from controlled conditions. Results from just the first of three years persuaded the city to use STAR, an intensive, one-on-one program developed by the University of Oregon, in more than 50 classrooms.

Children's autism center grew partly out of president and CEO Steven M. Altschuler's decision to target new technologies to areas where they could have the greatest impact, said Tom Curran, deputy scientific director.

"Autism was definitely something that we felt CHOP should be leading the world in," Curran said. The center is among the largest of the hospital's 10 "Centers of Emphasis," with more than $30 million in research grants - not counting many millions more in gifts, such as $4.5 million from the foundation run by Eagles owner Jeffrey Lurie, who has an autistic brother.

To attract the enormous numbers of participants needed for research, the center last year launched autismMatch, a tool that allows volunteers of all ages, with or without autism (the latter are needed as controls), to complete a 30-minute questionnaire that is then used to match them with appropriate current or future studies. The goal is 10,000 volunteers; more than 1,500 have signed up.

Besides research and treatment, the center periodically holds all-day boot camps for parents and a free lecture series on such topics as financial planning and children's anxiety. In a few months it expects to launch an online "autism services road map" that will include a directory of several hundred professionals around the region.

Many of the researchers are on the University of Pennsylvania medical school faculty. Some are affiliated with another center, in the nursing school, that focuses on the disorder's prevalence in Southeastern Pennsylvania. Elsewhere, St. Joseph's University offers autism education for students, teachers, and parents. West Chester, Lehigh, and Thomas Jefferson Universities provide training. (Details: www.philly.com/autism.)

Navigating the system was a challenge for the Yocums, who have cobbled together more than 30 hours of services a week for Amanda: occupational, play, speech, and special-education therapists, not to mention having professionals "shadow" her in summer camp and nursery school. Even with private insurance and free government services, they pay out of pocket for 90 percent of the costs.

Many of the therapies were recommended in the 12-page evaluation that was done when Amanda participated in the Children's study two years ago.

The effort seems to be paying off.

Amanda is starting to talk, and show interest in other people. She attends regular nursery school.

"Last year, I thought she was going to get kicked out," Beth said the other day. "This year, she is sitting at circle time with the kids, sitting right next to them. She's just basically able to participate in all the activities that are happening in the classroom."