Why Genetics Matters in Autism Research

How does genetic research benefit people living with autism today? And why do scientists do autism research on mice? Those are two of the questions I discussed with researchers at this year’s IMFAR autism science conference.

We’ll start with genetics, an area of study that’s often misunderstood . . .

The available evidence suggests that autism has both genetic and environmental components. When you study autistic minds at the cellular level, it’s possible to find many subtle differences between the brain cells and structures of people with autism and our nypical counterparts. Researchers are working hard to look at those differences and why they occur. At first, scientists thought we were born a certain way, but that thinking has evolved. Now most scientists believe our genes give us a predisposition toward something but both genes and the environment shape the final result.

Adding to the complexity of this is that “environment” is a catch-all word for many different things, including the air we breathe, our food, our water, and even the social community where we’re parented and raised. We are truly the product of the genetic material we start with and everything we encounter from that point forward.

Researchers have been cataloging autistic differences for some years now. Essentially, they start with the observable manifestation of a difference (like ignoring the people around you, or failing to communicate in the normal ways) and work backward till they find a possible biological reason why. For example, a first clue might be an area of the brain that’s too large or too small. Research biologists look at smaller and smaller structures until they get to the smallest difference, which might be an error in the DNA code for those cells.

Having found an abnormal part of the brain, and a possible genetic explanation, they now need to test their ideas out. That’s where the mice come in.

You may have read stories about our gene splicing and engineering skills. Genetic engineering has given us many things, from cloned sheep to drought resistant corn. It also gives us a powerful tool to study complex disorders in humans. In these experiments, mice stand in for people.

By introducing the genetic mutations we discover into mice, we are able to observe changes in their brains and even their behavior.

Why mice?

As it happens, mice are uniquely suited for this work. They are genetically very similar to humans, with over 99% similarity in the areas of the brain we’re studying in autism research. Almost every human gene has its analogue in a mouse. Mice are also social animals, making it possible to observe the impact of genetic changes in their behavior. Finally, mice grow fast and are relatively inexpensive to raise.

The human genome has about 3.2 billion base pairs, with about 25,000 actual genes. In a stroke of great fortune for scientists, almost every human gene can be found in a mouse. Mice have fewer base pairs than humans, but their gene count is about the same. Researchers can insert actual human DNA into mice genes, and then breed a population of altered mice for study. This sort of work has been extraordinarily valuable to medical science, giving us insights we just couldn’t get any other way.

When we introduce a human genetic aberration into a mouse we are able to see for sure whether that change introduces a structural change in the mouse’s brain. But more important, we get a chance to learn how such a change impacts the mouse’s behavior. Indeed, we are finding genetic differences that do actually translate into autistic behaviors in mice. For example, some differences make normally social mice totally ignore other mice in a cage. Other differences make the mice wring their “hands” and flap in a pattern of behavior that’s striking similar to human autistic stimming.

Once scientists have a mouse that exhibits a particular autistic trait, it is then possible to experiment with therapies to correct the problems. That’s where we are now with a number of genetic differences associated with autism. We are also able to study the relationship between a genetic difference and the environment with mice.

Some of the best-known examples of this work can already be seen in the grocery store, or the hardware store. Just look at the label warnings that tell you repeated exposure to a certain chemical causes cancer. We see those warning labels on packages everywhere. We identify cancer-causing chemicals by exposing mice to a particular compound and seeing if they develop cancer. In the autism world, researchers have looked at exposure to high levels of lead, mercury, and other chemicals to learn how they affect the developing or developed mouse brain.

One day, thanks to this sort of research, we might have labels that say, “Warning - Exposure to xxxx can cause autism.” There may indeed be environmental toxins that trigger autistic regression in people, and there may be chemicals that make autism like mine worse. If I knew what they were I’d be sure to avoid them – any of us would – but science needs to identify them first.

We know some chemicals are dangerous. Most of us already avoid heavy metals and other known toxins. My concern is that we may find other common but currently ignored compounds that are safe for some people but dangerous to others of us on the spectrum. For many of us, that knowledge cannot come soon enough.

On a hopeful note, we can also try various drugs, some of which can minimize or fix damage that started in the genetic code. For example, researchers have recently found that people with autism have excessive brain plasticity. Plasticity is the ability of your brain to change in response to life circumstances. Plasticity is essential to learn new skills, but too much of it can prevent you from learning much at all, because your mind can’t “take a set.”

We know how to create mice with excess plasticity, and we are now studying the effectiveness of drugs to reduce plasticity in abnormal mice. It’s both safer and faster to try these new drug therapies in mice, because they develop so much faster than humans. That work may – hopefully – lead to promising discoveries that can be tested in humans and perhaps ultimately lead to new therapies for that particular component of autism.

It’s important to keep in mind that we are not creating “autistic mice.” Autism is an extremely complex disorder, to the extent that many people say no two autistic people are the same. What we’re doing is modeling specific autistic differences by finding genetic codes that are associated with them.

That sounds easy, but it’s not. One problem is that a social behavior – like ignoring your fellow mice – might be associated with more than one genetic difference. In humans, we have hundreds or even thousands of subtle differences associated with autism. And no one genetic difference is common to all of us.

That’s why this is such a hard problem to unravel. We can isolate a difference, and even develop a therapy to fix the changes it causes, but that difference may only be present in 1% of the autistic human population. So what do we do for the other 99%? We continue our studies of mice and men, I suppose.

Some people are critical of genetic research in the field of autism, because they fear it may lead to prenatal screening and the abortion of autistic fetuses. I participated in many discussions last week, and I can say with certainty those ideas were not even on the table for the scientists involved.

Others criticize genetic studies because the think (wrongly) that the work won’t benefit anyone living today. However, the stated goal of much of today’s work is indeed to help the current autistic population.

No one can say what the full ramifications of any particular work may be, but I hope they ideas I’ve shared here make the importance of ongoing genetic research clearer. There is indeed a very good possibility that genetic research today will lead to therapies to mitigate certain components of autistic disability well within our lifetimes.

I sure hope so.

This story was originally posted on my Psychology Today blog