Autism prevalence has been rising steadily since the 1990s but despite extensive research, a genetic cause has not been identified. Experts from the Mount Sinai Institute for Exposomic Research explain how studying the environment can help prevent and better treat autism.
We spoke with Robert Wright, MD, MPH, Manish Arora, BDS, MPH, PhD, FICD, and Avi Reichenberg, PhD about how they’re applying exposomic approaches and methodologies to study autism risk and prevention. Read the excerpts from the interview below.
How are autism and exposomic research integrated?
Dr. Wright: Autism is traditionally thought to be a genetic disease. However, people have been studying the genetics of autism for about 20 years now. And in fact, we’ve now done whole genome sequencing on thousands and thousands of children with autism. And we haven’t been able to find the genes, so to speak, for the common forms of autism. At the same time, autism is becoming more and more common in our society. It’s actually impossible for genetics to explain an increase in autism rates because genetics takes multiple generations in order to cause changes. Only environment can cause something to change that quickly.
So, exposomics is really the key to understanding why some children get autism and some don’t. We’ve tried focusing purely on the genetics of autism, and we haven’t found the genes for autism and that’s because the genes don’t operate by themselves. They have to have some sort of environmental factor that they interact with.
Dr. Arora: I was always focused on the environment when it came to solving the autism puzzle. The reason was very simple. The year I was born, the prevalence of autism was one in 5,000. Now it’s one in 50 – that’s a 10,000% increase. As Dr. Wright mentioned, our genes don’t change so quickly. I knew the answer would never just lie in genomics. There had to be an environmental component, and that’s where I started to focus. It’s not that genes are not important. Autism is a heritable condition, so there is a genetic component, but the answer to autism and other complex diseases will never lie solely in genomics. When it comes to autism, the value of the exposomic approach is that it’s not trying to correlate one exposure to one disease outcome, because complex diseases don’t work like that. Rather, what it’s saying is that there’ll be many, many factors that each contribute a little bit, but together they raise a person above the threshold, where you end up having an autism diagnosis. That’s a very elegant approach for complex diseases, because we are no longer looking for that magic bullet, because there is no such thing for autism. By combining all the environmental factors and studying them in the context of genetic risk, we are getting much more clear answers, at least in my own research.
In what ways can exposomics change or impact autism research?
Dr. Reichenberg: In the past, we haven’t invested enough in research on environmental factors on autism because we haven’t collected the right kind of samples, because we didn’t have the right technology, because we didn’t have the right statistical tools to probe those environmental factors. Now, we do – and that can be a game changer in the research on environmental factors in autism. There are methods that have been developed here at Mount Sinai to probe environmental sources of risk and tools for data analysis and to disentangle all the information that comes from the environment into a clear signal. What we are trying to do here is not just disentangle the risk factors that are in the environment for autism, but also when is it risky. It might be that something increases risk for autism if the baby is exposed to it in the second trimester, but not in the third, and not after birth, and not even in the first trimester, it might be that the risk happens after birth. It might be that the risk happens in the second half of pregnancy, but not in the first half of pregnancy. We need to measure it with the right tools, and we need to measure it at the right time.
Dr. Arora: The reason exposomics is a game changer in solving the autism puzzle is something that we became aware of in our own research. Currently there is no diagnostic test for autism, even though it’s a heritable condition, therefore we know it exists at birth. The earliest we can detect autism is around the age of three or older, and there’s a huge disparity there. If you are a poor child of color, then your diagnosis happens later. This is a big problem because our brain is developing so quickly, the chances of delivering therapy and the impact of that therapy diminishes very quickly as we get older.
The sooner we diagnose autism, the bigger the impact therapy will have. By using an exposomic approach, and by accepting that the environment is dynamic and not static, we have developed a test that uses a single strand of hair, that maps a person’s metabolic dynamics as an interface between the genes and the environment and delivers a result that’s over 90% accurate in helping diagnose autism as early as birth. This is a world first and we are currently working with the FDA to see how we can bring it to every child in the United States, after that globally.
Dr. Wright: Unlike genetics, the exposome can actually be modified because it’s our environment. So the potential to prevent autism is far greater in exposomics. Investigating deeper into the exposomics of autism, we can start to develop therapies to reduce the effects of autism in children, or even prevent the disease altogether.
How can teeth and hair help us understand the exposomics of autism?
Dr. Reichenberg: These tiny baby teeth that we analyze hold within it an ocean of information. And with methods that Dr. Arora and Dr. [Christine] Austin here developed, you can probe this tooth and extract histories of exposures from in utero and until the tooth falls out. And it’s an enormous amount of data, data that we didn’t have until about five years ago, that we couldn’t get. We can pinpoint exactly when an exposure happened, from the middle of pregnancy and until age seven. And that is the kind of information that, when you collect, you can talk about exposome and environmental exposures.
Dr. Arora: The key to this innovative test was this idea that there are signatures in our body that can only be seen in the time dimension. So, the idea is actually very simple. If you’ve ever looked at a tree that has been cut down, you will see growth rings. And you can map the qualities of tree growth backwards in time. There are many tissues in the human body. Much of my earlier work was on baby teeth. Teeth have growth rings in them. Recently we’ve started looking at growth rings in human hair. What we find is that the signatures that are specific to autism can only be discovered if you have a sequence, a temporal sequence of measurements of key biochemical pathways. In one way to understand this, is to think of it like a song. To understand a song you can’t just take a snapshot and listen to it for a fraction of a second. You need to know the notes that came before and the notes that come after to understand the full piece of music. And that’s exactly what we are doing with autism. We’re using a strand of hair like a vinyl record. It has growth rings and as we map across it, we find these dynamic rhythms that are characteristic of autism.
The difference between teeth and hair is that teeth allow us to go back much further, even before birth. So, we can go years in the past. Whereas hair is a reflection of more recent history. However, hair offers an advantage that we can collect it noninvasively at almost any time wherefore baby teeth, we have to wait until they are shed.