Judy Van de Water got into autism research precisely because she wasn’t an expert in autism. She is an immunologist, studying the strategies our bodies employ to defend us against pathogens, and the ways those strategies sometimes misbehave or overreact. But about 15 years ago, the then-new MIND Institute, which sought to bring fresh eyes to understanding disorders of brain development and function, set up shop near her lab at the University of California, Davis. When the institute asked for grant proposals from specialists in fields outside brain development, Van de Water heeded the call.
Her proposal eventually led her to pursue an outsider idea: the possibility that immune responses in an expectant mother’s body, unleashed in the wrong place at the wrong time, can interfere with the development of the growing fetus’ brain. She now holds that this immune activity could be the cause of nearly one in four cases of autism. In particular, Van de Water blames a certain set of antibodies, immune molecules designed to target invading infectious agents and destroy or neutralize them. She’s so sure she’s right that she refers to it confidently as ‘MAR,’ or ‘maternal-antibody-related autism.’
From the start, it was a provocative theory that ran counter to prevailing beliefs about both the immune system and autism, and in the early days Van de Water was one of its few proponents. “We’ve been swimming upstream — still are,” she says. Her peers criticized Van de Water’s work on the grounds that her results didn’t support her claims. And they were deeply upset when, in 2013, Van de Water formed a licensing partnership with a San Diego-based company called Pediatric Bioscience. That deal was aimed at developing a maternal antibody screen that might allow for early diagnosis of autism or, if performed prenatally, indicate the risk of having a child with autism. “This is very, very premature,” Yale University autism researcher George Anderson told Science at the time.
Still, despite the controversy, the basic idea underlying Van de Water’s work — that maternal immune activity can increase risk for some types of autism — is edging into the mainstream. Researchers from other labs are exploring the consequences of maternal immune activity. Some teams are investigating a second immune pathway, involving cytokines, signaling molecules that coordinate the response to infection. Their results, showing that antibodies and cytokines are both capable of producing autism-like symptoms in mice, have been reported in the past year in prestigious journals and at high-profile conferences.
The implications of this idea could be a huge deal for families. It should be possible to offer a test that screens a woman for the antibodies that might trigger autism, just as Van de Water hopes to do. “Testing for the presence of a particular antibody is something that, in principle, we know how to do,” says Betty Diamond, an immunologist at the Feinstein Institute for Medical Research in Manhasset, New York, who is another leader in the new field. What’s still unclear is how accurately such a test in a woman would predict autism risk in her child. Diamond is instead focusing her lab’s efforts on prevention. She envisions treating a woman who carries the harmful antibodies with a relatively benign medicine that would neutralize the antibodies. “We want to develop something that’s safe enough that if we give it to 10 times the number of people we need to in order to protect one fetus, we haven’t done any damage at all,” says Diamond.