For a decade, the government, public- health experts and medical groups have said there is no credible scientific evidence - none - that vaccines cause autism.
Then came Hannah Poling, a 9-year-old from Athens, Ga. A federal program created to compensate vaccine-injury victims conceded that her autism is linked, albeit indirectly, to immunizations she received as a toddler.
Hannah's case, made public by her parents in March, is unusual and circumstantial, yet it is building mainstream support for a notion long considered dangerously misguided: There may be subgroups of children who should not be vaccinated - or at least, they should get fewer shots over a longer period.
Bernadine Healy, former director of the National Institutes of Health, risked "incurring the wrath of some of my dearest colleagues" to express that opinion in U.S. News & World Report.
"Yes, vaccines are extraordinarily safe and bring huge public health benefit," she wrote last month. "But vaccine experts tend to look at the population as a whole. . . . And population studies are not granular enough to detect individual metabolic, genetic, or immunological variation that might make some children under certain circumstances susceptible to neurological complications after vaccination."
Geraldine Dawson, chief scientific officer of the advocacy group Autism Speaks, declared that the Poling case "shines a spotlight" on the issue of unusual sensitivities.
"We need to conduct research to better understand and identify subgroups of children who may respond poorly to vaccines," said the former University of Washington developmental-psychology professor.
Hannah's case is complex because of an abnormality involving her mitochondria.
Called the "powerhouses of the cell," mitochondria are microscopic structures that convert oxygen and nutrients into energy. When they malfunction, the cell may be so starved for energy that it is damaged, or even dies.
Defects in mitochondria - first linked to disease only 20 years ago - are now known to cause a long list of problems, including seizures, migraines, strokes and digestive abnormalities. Depending on the extent of mitochondrial dysfunction, the stress of "even a simple flu or cold virus" can worsen symptoms, says the United Mitochondrial Disease Foundation, an advocacy group.
Mitochondrial defects occur in about one in 10,000 people, but their role in autism is unclear. The few studies that exist suggest at least 7 percent of autistic children have these abnormalities.
Hannah is one of them.
Her father, neurologist Jon Poling, and mother, Terry, a registered nurse and lawyer, believe a battery of nine vaccinations Hannah received when she was 19 months old contributed to her transformation from an alert, verbal toddler to one with autism. She stopped communicating, wouldn't make eye contact, and fixated on lights.
The Polings spent a year seeking a medical explanation for her developmental regression before tests of her blood and muscle samples revealed abnormalities of mitochondrial function.
The parents turned to the federal Vaccine Injury Compensation Program, created in 1986 to offer an efficient, "no-fault" alternative to lawsuits that were driving vaccine companies out of the business. Claimants need to prove only that a vaccine caused injury, without placing blame.
Medical personnel at the compensation program reviewed Hannah's file but did not hold a hearing. They conceded the immunizations "significantly aggravated" her underlying cellular disorder, causing neurological damage with features of autism.
Hannah's case is not representative of the backlog of 4,900 petitions filed by other families. Those parents argue that the measles-mumps-rubella shot, a mercury-containing vaccine preservative called thimerosal, or the combination, caused their children's autism. (Most vaccines no longer use thimerosal.)
The compensation program is now hearing nine "test" cases that represent these three causation theories. Decisions are not expected before next year.
The program, supported with an excise tax on each vaccine dose, has so far awarded about $890 million to compensate 2,140 claims, but Hannah's is the only one known to involve autism. The fund still has $2.7 billion.
Despite the concession in Hannah's case, experts say the idea that a cellular energy deficit could be aggravated by stimulating the immune system with vaccines is speculative.
Columbia University neurologist Salvatore DiMauro, an expert in disorders of cellular energy metabolism, said: "I like to say we're dealing with three dots. Two dots have been reasonably connected - autism and mitochondrial disease. The third dot - vaccines - has not been connected in any evidence-based way to autism or mitochondrial disease."
Says the mitochondrial-disease foundation: "There are no scientific studies documenting that . . . vaccinations cause mitochondrial diseases or worsen . . . symptoms."
Public-health officials also point out that for anyone with mitochondrial dysfunction, the theoretical danger of vaccines is far less than the real danger of diseases they prevent.
But that suggests, incorrectly, that the Polings are urging parents not to vaccinate their offspring at all.
"I really don't want that to happen," Jon Poling said in a phone interview.
What the Polings advocate is research into the possible role of mitochondrial disease and vaccines in autism.
That, they hope, would lead to screening tests to identify children who could benefit from customizing the standard vaccination schedule, which has grown from 10 shots against seven diseases in 1980 to the current 28 shots against 14 diseases, not including the annual flu shot. (Vaccine experts counter that the total number of immune-stimulating proteins in the shots is lower than ever.)
Hannah had missed the vaccinations usually given at ages 12 months and 15 months because of recurring illnesses, so when she was 19 months old, her pediatrician followed guidelines to catch her up: He gave five shots against nine diseases all at once.
"If I were to do it over again," Poling said, "I'd just be extremely cautious, space the vaccines out, make sure her nutritional status was good and that she was very healthy."
The American Academy of Pediatrics says "it is not advisable to skip or delay vaccines." But many doctors are becoming less dogmatic as parents ask about the persistent vaccine-autism controversy.
Atlanta pediatrician Jennifer Shu, a spokeswoman for the pediatricians' group, said that in deference to parents, she has spread shots out over weeks. She also ordered a blood test that showed a 5-year-old autistic child had enough immunity to postpone the measles-mumps-rubella booster; now 11, he is being retested to see if he needs it.
"If it's something the parents feel strongly about, I try to work with them to find a way to protect the child," she said.
Whatever the cause of autism, federal data show it has become common. One child in 150 is now diagnosed with some form of the disorder, compared with one in 2,000 in the early 1980s. Recognizing that the most severely affected need lifelong therapy and support, Gov. Rendell announced last week that Pennsylvania is extending Medicaid-funded autism services to a few hundred people over age 21, the first state to do so.
Poling won't discuss how much compensation his family will receive, because part of the award is undecided. Equally important, Poling said, Hannah's case "has raised many intelligent discussions and questions."
"What happened to my daughter won't be in vain if it leads to a safer vaccine program," he said.