WASHINGTON, May 13 (UPI) -- When Timothy Baltzley of Olympia, Wash., went for his 1-year-old well-baby checkup in December 2000, his mother was invited to enroll him in a clinical trial of experimental chickenpox vaccine.
The eight-page consent form said two versions of a "process upgrade" vaccine manufactured by Merck & Co. were being compared. Children ages 12 to 23 months would get one of the shots at random at the same time as their standard measles-mumps-rubella inoculation.
Known as P31 and P32, the chickenpox shots were "investigational vaccines, which means they have not been licensed for marketing by the U.S. Food and Drug Administration," according to the consent form.
Timothy's mother, Kimberly Baltzley, signed the form and Timothy got the chickenpox and MMR shots on Jan. 3, 2001, a couple of weeks after his first birthday.
Everyone agrees on all that. But exactly why Merck was testing those chickenpox vaccines is in dispute, and just how much attenuated live chickenpox virus was in each shot is uncertain -- potentially significant facts given that Timothy later was diagnosed with autism.
Timothy was the first of two children in less than two years to develop autism in the same Olympia pediatric practice after participating in Merck trials involving chickenpox and MMR vaccines. The second child, Jimmy Flinton, got a four-in-one chickenpox-MMR shot called ProQuad in October of 2002.
Timothy's trial had 68 children; Jimmy's had 33. Along with participating in the trials, Timothy and Jimmy have in common unusual family backgrounds of problems with chickenpox virus.
Kimberly had mild cases twice as a child and then a severe case at 16, three years before Timothy was born; her 15-year-old sister, Amanda, had an even worse case at the same time, leading to scars and ongoing balance problems from pox in her inner ear.
Jimmy's paternal grandmother had shingles -- the reactivated form of the virus -- at 20 and recurrent cold sores that led to herpesvirus in her corneas; Jimmy's father had shingles at 16. Shingles usually afflicts older people or those with weakened immune systems.
Parents of other autistic children the same age who lived in the same Olympia neighborhood say they saw a similar pattern: an unusual history with chickenpox and other herpesviruses in their families; separate, but in most cases simultaneous, MMR and chickenpox shots by 15 months; and the onset of regressive autism in their children prior to 18 months of age.
While Merck and federal health authorities say there is no evidence of a link between vaccines and autism, a minority of researchers are concerned that inherited susceptibility to viruses in vaccines might constitute an unrecognized risk factor. They say the Olympia children may be troubling cases in point, underscored by Jimmy's and Timothy's diagnoses after similar clinical trials.
The consent form Kimberly Baltzley signed for Timothy made no mention of the amount of vaccine in the "process upgrade" chickenpox shots. But she said her pediatrician told her it was significantly higher than the standard shot because the trial was part of the development of a combined chickenpox-MMR vaccine -- the shot Jimmy received two years later.
Combination vaccines can require higher doses to overcome a phenomenon known as interference, in which viruses undercut each other's ability to trigger an immune response.
"My understanding at the time was they were trying to combine the MMR and the chickenpox," she said one recent evening while straightening up after a meeting of a local support group she heads up for parents of autistic children.
"The way it was explained to me was they knew that when they combined them, they had to increase the amount of chickenpox that was in there," she said. "(The doctor) said the worst thing, barring some kind of an allergy or other reaction we don't know about, is that there is so much chickenpox virus in there that kids will catch the chickenpox. That's what they were trying to figure out.
"They (the shots) were given separately because, I was told at that time, they had not been given the OK to combine them," she said.
"What they were trying to do was get the OK."
A neighbor of the Baltzleys whose daughter was in the same clinical trial was given the same explanation, she said.
Merck, however, offered an entirely different explanation of the trial, saying it had nothing to do with developing the four-in-one ProQuad shot.
"Please note (the study) was NOT a trial of ProQuad nor was it conducted for any reason related to ProQuad," Merck spokeswoman Christine Fanelle said in an e-mail response to questions from United Press International.
"It was a trial we conducted in preparation for a process upgrade done for manufacturing purposes only," she said.
When UPI sent Kimberly Baltzley's description of the trial to Fanelle, she responded: "All I can do is confirm once again that our records indicate that (the pediatrician) participated in the two trials I noted."
Fanelle did not directly respond to a question about how much chickenpox virus was in the process-upgrade shots, saying that "P31 and P32 work the same way -- both stimulate antibodies against the varicella (chickenpox) virus. The manufacturing process is what would differ in subtle ways.
"Further details around our manufacturing process upgrade varicella vaccine are proprietary for competitive reasons," Fanelle said. The FDA did not respond to requests for comment about the trials. The Olympia pediatrician, Dr. Carl A. Lindgren, referred questions to Fanelle.
Also at issue is when and why Merck alerted the FDA to the two autism cases. Fanelle told UPI that Merck "just received these reports in March 2006 and they were sent to the FDA after we received them." That was the same month UPI first raised the issue with Merck and the FDA.
Fanelle said Merck received the reports from parents.
Kimberly Baltzley and Jennifer Flinton said they didn't make any such reports. "If they want me to call them I will," Kimberly Baltzley said when told of Merck's account, "but I don't have their number."
What did happen, she said, is that nearly five years ago, she returned with Timothy to her pediatrician, concerned about developmental delays and strange behavior in the months since his participation in the study. The doctor said Timothy should be evaluated by experts, and he subsequently received an autism diagnosis. They also discussed the chickenpox-MMR trial and the controversy over whether vaccines can trigger the disorder.
"He told me, 'I don't think they had anything to do with each other, but I have to report any kind of problem to the trial.' He told me that back in September of '01. Dr. Lindgren is a very conscientious person so I know he probably reported it that week."
In Jimmy's case, Jennifer Flinton said she called the federal government's Vaccine Adverse Event Reporting System last summer. She attributed Jimmy's autism to the cumulative effects of vaccination, although she did not specifically mention the 2002 ProQuad trial.
The employee who spoke with her said she would follow up by obtaining Jimmy's vaccination records for an official adverse event report.
ProQuad was approved by the FDA last September. Because of immune interference among the components, Merck's Fanelle said, "we had to increase the varicella component," but she did not specify the amount. Other officials have said that amount was "about a log," or ten times, higher than the standalone Varivax chickenpox shot.
"However, our studies showed the same safety and immunogenicity profile was seen with ProQuad compared to the profile seen with the two vaccines administered as separate shots," Fanelle said.
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