More than 3.5 million Americans today live with autism, a condition without a cure. But that's not to say that children with autism don’t take medication. According to a survey by the National Institute of Mental Health, more than half of children with autism ages 6 to 17 are on one or more more drugs normally given for disorders like anxiety, depression, psychosis or hyperactivity. But what if there was a way to treat these children without ever making them take another pill?
This is one of the more intriguing ideas to come out of the genetic revolution spurred by the discovery of a gene-editing technique called CRISPR-Cas9, a method that allows scientists to make precise changes to DNA sequences in any living organism, human or otherwise. Researchers are already using this technique in a vast range of projects, from creating mildew-resistant wheat to reversing mutations that cause blindness. In China, scientists have used CRISPR to edit human embryos, an announcement that set off an explosion of ethical concerns. (The scientists used embryos that could never have been brought to term, and fewer than half the embryos were edited successfully.) We are probably still years away from scientists being able to correct genetic flaws in human embryos. But what might come sooner is the ability to treat or cure diseases in children and adults, perhaps by injecting them with a CRISPR-equipped virus that will be able to correct whatever genetic defect contributes to a given disease.
At the McGovern Institute for Brain Research at MIT, scientists are using CRISPR to try to better understand -- and ultimately, develop cures for -- brain diseases and mental illnesses that have eluded us until now. “I see some glimmers of promise on the autism horizon,” Robert Desimone, a professor of neuroscience and the director of the McGovern Institute, told The Huffington Post. “This is opening up all kinds of possibilities for both understanding the pathophysiology of the disease and then targeting that pathology for new treatments.”
HuffPost spoke with Desimone this week about the possibilities and challenges of the new technology, and about how CRISPR could lead us to what he calls a post-pharmaceutical age.
Let’s start with the basics. Where are we now when it comes to CRISPR, brain diseases and mental illness?
In the last few years, the biggest advance that’s been made in understanding the basis of all forms of mental disorders has been in genetics -- identifying risk genes for all the major psychiatric disorders. And that is opening up all kinds of possibilities for both understanding the pathophysiology of the disease -- what’s going wrong in the brain -- and then targeting that pathology for new treatments. So that’s the greatest opportunity.
The greatest challenge is, how do you go from genetic knowledge to these new treatments? Because you’re talking about genetic vulnerabilities that may affect the development of the brain, but they may be expressed only years later. Take schizophrenia, where everyone thinks it’s a developmental disorder and something's going on in the womb, but then you may not see anything until the person is 20 years old. There’s a lot going on there. You want to understand what’s going on at a cellular level, but then there’s also the need to understand how all these cells work together. The brain is not just individual cells, doing their thing. It’s all these cells working together.
CRISPR’s impact is potentially across the board. It went from nothing just a few years ago to being a tool that’s in everyone’s toolbox. I mean, everyone is now incorporating it into whatever it is they’re doing, all the way from cell-based models up through therapeutics.
Before CRISPR, when people were trying to understand brain diseases, what tools did you have for identifying the diseases and developing treatments?
There have been different tools available, but they all had major limitations. Typically, they’re limited to manipulations of one gene, whereas with CRISPR-based methods, you could potentially manipulate many genes. And one of the things we’ve understood about psychiatric disorders is that in most cases, most diseases do involve multiple genes.
And then there’s the question of how you could study these genes. With animal models, all animal models were based on certain lines of mice that had unique properties that allowed you to manipulate their genomes. CRISPR has expanded that to any species. And even within mice, it offers many advantages.
What are the implications of that -- the fact that now we can manipulate the genome of any species?
That’s one of the reasons that the National Academy of Sciences formed a committee to consider the ethical implications of CRISPR. Because when I say it can be used in any species, that includes humans, and there is a fear that people will start human embryo manipulations. I would say a huge majority of scientists and clinicians think that it would be way premature at this stage. So I anticipate the National Academy will issue some strong advice, and a moratorium on the use of CRISPR in human embryos. And that’s not to say it will be a ban in the future, but until the risks are better understood, and until the technology is further developed, and until we have a chance to really work through all the ethical implications, there will be a lot of pressure to keep this out of human embryos.
But in other animal models, it could potentially be applicable in any of them, and in very powerful ways. It can be done quickly, it can be done cheaply.
How could you potentially use CRISPR to understand or treat something like depression, or other kinds of mental illnesses?
Of all the psychiatric diseases, depression has probably got one of the least strong genetic components. There are a lot of purely environmental effects that lead to depression in people, whereas with something like autism and schizophrenia, the genetic contribution is a lot higher.
So for one, if you can identify a genetic cause of the disease, then you start looking at targeting the cause. If there’s something going wrong at the cellular level, you can target the receptors of cells, like how we do using common drugs, or you could potentially target the DNA of the cell that gets at a deeper level of some of these regulatory functions. There’s a whole range of things you can do using genetic tools to manipulate how cells work.
Or let’s say you have someone who has no genetic vulnerabilities, but as an adult, they are subjected to something traumatic -- let’s say, abuse -- that leads to depression further down the road. There’s a lot of interest in identifying the genetic regulatory changes that are taking place in cells in response to the abuse that leads to the depression. Now you’re talking about something CRISPR could well be used for.
So we might begin to understand how our cells react to trauma, and use CRISPR to somehow combat that?
Yes. How cells are affected by trauma, and ways that we might influence cells to negate those effects. It could be that whatever therapeutics eventually come out could be potentially based on CRISPR.
In your mind, what’s the most exciting way that CRISPR could be used on the brain, and to combat mental illness?
These are really early days, and the methods themselves are changing month by month. With Feng Zhang here [the molecular biologist at the Broad Institute of MIT and Harvard, who is one of the scientists credited with developing the CRISPR method], he comes into my office telling me about some new advance literally every month. I don’t know what CRISPR is going to be doing six months from now, because everything Zhang tells me, I haven’t even imagined.
Here, Feng Zhang is working on creating autism models, and I’m pretty excited about how that project is going. It’s a little early to talk about, but I see some glimmers of promise on the autism horizon.
What would these treatments be like?
They could be, for example, a virus that you would give the person that would carry genetic material ... Feng has developed a smaller version of a cas9 enzyme that can fit in a common virus that’s used in gene therapy, and so that would be one possibility. Wouldn’t that be interesting, that if someone had autism, you would give them a viral injection and they might never have to take a drug after that? Some people are talking about what could potentially become the post-pharmaceutical age, where the treatments that we have don’t necessarily look like pills that you take every day.
How would that injection work?
The very simplistic idea is that the virus would be created so that when you inject it into the person's bloodstream, it carries the relevant genome-editing machinery into the cells, so that it corrects the genetic defect that contributes to the disease.
Were people thinking about this idea before CRISPR -- the post-pharmaceutical age?
CRISPR stimulated it. The idea has been around for quite a long time. But CRISPR has opened new avenues.
But I think that people have to be concerned about not over-hyping. Don’t over-promise, don’t over-hype, don’t lead people to think that cures are just around the corner. We can’t underestimate -- it’s going to be a real struggle scientifically to make the kind of progress that’s been stalled for so many years. A lot of these disorders, there hasn’t been a new treatment for decades. It's not going to change overnight. But we have a new promising direction.
Lila Shapiro covers the science fiction of science, the imaginative ways scientists are trying to solve the world’s hardest problems. Tips? Email Lila@huffingtonpost.com.