Interview with the World's Most Celebrated Virus Hunter: Ian Lipkin
part 4
If the identity of the infection isn’t critical, what is?
The important things are the genetic background of the individual and the timing of the insult. If you look at the original work on the epidemiology of thalidomide [a morning-sickness drug that turned out to cause birth defects], there were specific time points where, if the woman was exposed, the baby had a high probability of having bona fide autism.
One of the most fascinating links between infection and mental disease concerns PANDAS, pediatric autoimmune neuropsychiatric disorders. The bottom line is that strep might cause obsessive-Ӭcompulsive disorder. How could that happen?
An infection like strep throat provokes an antibody response, but the antibody created to fight the strep also recognizes proteins that are part of your body. Antibodies don’t typically traffic much in the central nervous system. But if you have any one of a number of other infections or an insult like head trauma, the blood-brain barrier [which normally protects the brain from pathogens] opens transiently. Depending on how long and where the opening is, the antibodies get access to part of the central nervous system or brain. We are studying this process now in mice, using drugs to open up a portion of the hindbrain or the forebrain or the hippocampus and tracking the effect.
Could autism be another version of a PANDAS-like disease?
It’s possible, in some people. There is probably a group of people who have a genetic component to autism, and for them, there may not be much of a trigger or any trigger at all required. Another group is genetically predisposed, and if they encounter some factor or factors, individually or in combination, it could result in either the onset or the aggravation of the neurodevelopmental disorder; by factors, I include everything from heavy metals to infection. And lastly, there is a group that may be relatively or entirely normal but is exposed prenatally to some factor or factors that have an effect on their nervous system and that manifests as autism. This is the hypothesis, at least.
You are trying to put all this research together through a prospective study called the Norwegian Autism Birth Cohort. What’s that about?
The idea is that you can get only so far by examining people when they’re sick, because the seeds of illness may be laid many years before. In a prospective cohort, you can follow children ”¨from before birth in an unbiased way, collecting information and samples and maybe making associations between factors and outcomes after the fact. We’re going back as far as we can, which is the first prenatal visit at roughly 17 weeks’ gestation. And the study is being done in Norway because there’s universal health care; you don’t have to be concerned about discrimination for insurance purposes based on disease, and as people get ill, you have long-term follow-up.
What could that study tell you about the nature of autism?
We have thousands of biological samples that will be transferred back here to New York, and we’re going to analyze them using all the tools of microbiological analysis we developed to look at acute diseases in the past. Because we have blood samples that are obtained from the mother during the course of pregnancy and at the time of birth, we can examine a whole range of proteins and messenger RNA s that may be reflective of genetic defects or exposures. We may not detect an autism-causing agent specifically, but we will see that there is a marked increase in specific biomarkers. This allows us to define in a very broad sense what proteins, nucleic acids, pathogens, and toxins might be part of the milieu of the fetus.
The next morning we went to the Great Hall. I’m told I’m there to design their SARS program.”
How would you describe your overall approach to pathogen discovery?
In microbe hunting we start with the result, the disease, and work backward, examining the paths and pathogens that might have led there. Finding footprints of a microbe””whether you’re seeing antibodies or the virus itself””is just the beginning of solving the crime. Initially the evidence is circumstantial. Like in criminology: Seeing a suspect on the street corner where somebody was killed is not enough. We still need motive and opportunity. Motive is tropism [seeking nutrients or energy] and virulence [ability to multiply and cause disease]. Some microbes are known to infect the lungs or the intestines or the brain. Finding them in a typical location gives us confidence we are on the right track. Opportunity””could it have done the damage? Some infectious diseases are seasonal. Mosquito-borne diseases, for example, are common in the summer but rare in the winter. Noroviruses are common on cruises. That’s where biological plausibility comes in.
You sound a lot like an old Hollywood detective.
If you can find a smoking gun, if you can show that this preceded that and somebody’s been shot in the past, then you can get a conviction. That’s exactly what it’s like.
Source:
More than a Nuisance: Managing Your Childs Food Allergies
More than a Nuisance: Managing Your Childs Food Allergies (part 2)
