Frampton Gwynette: Hello, I’m Frampton Gwynette with the Autism News NetWORK reporting to you from Montreal, Quebec. Canada is a very special treat for us. I’m here with dr Jeremy Veenstra-VanderWeele who is really one of the leading physician scientists in the field of autism and also a great friend. Jeremy, welcome.

Jeremy Veenstra-VanderWeele: Thank you. Thanks Frampton.

Frampton Gwynette: Yeah, Thanks for doing this. Now I have so many questions I want to ask you, but you’ve really been at this for a long time. And how many years would you say that you’ve been studying autism?

Jeremy Veenstra-VanderWeele: Well, I guess I started when I was about 20 more or less by accident. We was looking for a summer job and landed in a lab of a child psychiatrist who did genetics research. So yeah, about 25 years.

Frampton Gwynette: Wow. So even before you were out of college, you were-

Jeremy Veenstra-VanderWeele: Yeah. Feels like both very recently and forever ago.

Frampton Gwynette: Yeah, exactly. And so early on it sounds like you had the direction and just to let our audience know, most physicians do not actually become researchers. They actually work exclusively with patients for the most part. But Jeremy, you’re one of the rare breed that is a physician scientist. So what led you to kind of make that decision about your career path?

Jeremy Veenstra-VanderWeele: So I think like you Frampton, and I was interested in working with people one on one, being a clinician, being a doc, but was frustrated at how little we have to offer and fascinated to understand some of the biology that underlies the difficulties that that folks have. And you can only do that by… You can spend time in the library, but at a certain point you can only do that by asking questions and looking for answers. And that’s sort of what what drew me in. Although as much as anything, it was having examples of people who are doing just that. Examples of people who would work with a young person in the clinic and then carry that motivation into the lab and try to answer questions.

Frampton Gwynette: So you’re seeing patients in your clinic and they inspire you, and ask questions and find answers to clinical needs.

Jeremy Veenstra-VanderWeele: Yeah. And then, at a certain point the question start driving you on their own. So I think I asked myself periodically is, is what we’re asking, is the work that we’re doing in the lab important, that drives you to ask clinical questions again. But sometimes you make an observation, you think why? Why this? And then you spend more time following that. I try to continuously sort of turn back and and ask whether this is something that’s leading us in a direction that could turn into a treatment, turn into an understanding of what’s actually going on under the surface.

Frampton Gwynette: And that’s called translating, translational, yeah.

Jeremy Veenstra-VanderWeele: Yeah, I mean that’s, it’s sort of a buzz word that we talk about translational research, but it really means, and I think of it going in both directions. So, working with somebody with autism in the clinic, we’ll give you a question that you’ll turn to understanding biology to answer it. And then it has to go the other direction as well, that in the lab you find something and then you have to ask the question in people to figure out if it actually matters.

Frampton Gwynette: Yeah. And that leads me to start thinking about genetics because one of the things that’s interesting is patients can have blood testing now to have a chromosomal micro-array for instance, and they can discover that they might’ve been walking around with genetic mutations they didn’t know they had.

Jeremy Veenstra-VanderWeele: Yep. Well all of us have genetic variants that lead to risk of something and that can be the size of your nose, the way my ears stick out. It can be anything. And we know from looking at twin studies, for example, that genes clearly contribute to risk of autism. There are many different ways to have autism and autism as a term, autism spectrum disorder captures the idea that this is incredibly broad. It’s a series of three words that we use to describe somebody who might be a professor in college and somebody who might not be able to talk. And what we’re learning on the genetics front is that particularly in those people who have more difficulties, there are genetic variants that can be identified with simple blood tests.

Jeremy Veenstra-VanderWeele: So chromosomal micro-array, like you mentioned about 10% of the time if you send a chromosomal micro-array in any given person with autism, it’ll come back with a finding. That doesn’t mean that that genetic finding caused that person’s autism. What it does mean, however, is if you took that genetic finding away, that person probably would not have autism or would not have the same a cluster of difficulties they may run into. Most of those findings, however, are not in the folks who are in college right now or who are out in the professional world. Most of those findings tend to be in folks who have difficulties with learning difficulties with speaking, sometimes difficulties with motor function, et cetera. Although we do some find some of that also in people who may not have particular difficulties in any of those areas. It’s just a lower rate in that crowd.

Frampton Gwynette: And now I’m thinking about syndromic autism. Can you explain to the audience what that is?

Jeremy Veenstra-VanderWeele: So it’s when… 25 years ago you would say for example, that somebody has fragile X syndrome and you would say, oh, they don’t have autism, they have fragile X syndrome. And where things have evolved over the period of time from when I was very early in training in a lab to where we are now is we now say that that person has fragile X syndrome and they have autism, and we recognize that the term autism means a cluster of behavioral difficulties that might have clinically. It’s just a description and it’s a broad description. Whereas the term fragile X syndrome refers to somebody who has a specific genetic difference that leads to a cluster of difficulties. And so fragile X syndrome is one of the more common ones, but there’s a whole bunch of them, more than a hundred different syndromes that increased risk of autism, but none of them determine autism.

Jeremy Veenstra-VanderWeele: So in fragile X syndrome, about 30 to 50% of people have autism, but not everybody. Everybody has learning difficulties and some other symptoms, some other difficulties, but not always autism. So when we say syndrome, autism, what we really mean is somebody who has a defined genetic syndrome, a cluster of difficulties, you can blame on one gene or a region of their genome. And also has autism, so it’s something, there are two different things. It’s that it’s sort of saying that somebody has autism spectrum disorder in that context is sort of like saying somebody has diabetes related to this particular syndrome. It doesn’t necessarily tell you why it describes what somebody is struggling with.

Frampton Gwynette: That’s a great explanation. I think that’ll be useful for our audience. And then digging a little bit deeper on genetics, can you talk a little bit about why it’s important to develop animal models and then one specific question would be what’s a knockout mouse?

Jeremy Veenstra-VanderWeele: Okay, so there are things that we can only understand in biology by doing experiments and by and large we try to avoid doing experiments on humans. So in order to understand what’s happening in the brain in autism, you can’t take a biopsy. I can’t go in and take a little chunk of my brain and take it out and say this is how it works differently than in somebody else. Not in a way that anyone wants. You can do neuroimaging studies where you look at a more macro level, you look at a larger scale. This part of the brain is more active in this person than that person. But to understand what’s happening molecularly, you have to do an experiment, and in order to do that you have to do it in some sort of other systems.

Jeremy Veenstra-VanderWeele: So you can do it in cells or you can do it in a whole animal. Mostly when people do it in a whole animal, they do it in a mouse or rat or a fish, an organism that reproduces rapidly and where we know how to understand what is different. And so a knockout mouse is where you literally just take out some genetic material or disrupt some genetic material, usually to model something that’s happened in a human. So let’s say you have a gene that is involved in autism risk. You disrupt that gene in a mouse and look at the consequences in the brain in a way that you could do in a human. And you hope to learn something about how that genetic change leads to a change in the brain and sometimes behavior, but you’re really after what’s happening in the brain and then maybe get an idea of how you can take that and change it back or give a medicine that leads to improvement or put the animal in an enriched environment and see if that improves things.

Jeremy Veenstra-VanderWeele: So then you’ve done an experiment, you’ve done this genetic change, you want to understand how that’s affecting the organism and then you want to see if you can test that hypothesis that you now have to rescue something. And that’s where in the end you do an experiment in a human but with a whole bunch of knowledge. You ask, does this medicine or does this gene therapy or does this behavioral intervention actually change things for a person? But you want to do a lot of work first to understand the biology and test things to make sure that they’re safe, in an animal.

Frampton Gwynette: And I think it’s important, because it’s almost like a bottom up and there needs to be underpinnings, biological theory, and then test in an animal model and your work your way. And that process takes a long time. A lot of times, and I have patients, families who come in, they say, “Hey, can we try this supplement? Or that supplement?” But the work on underlying it hasn’t been done. It’s hard to recommend that isn’t it?

Jeremy Veenstra-VanderWeele: Yeah, yeah, yeah. No, that’s, there are a lot of things that are untested or under-tested. And the most important thing is to make sure that they’re safe, but you’d like to spend your time and energy doing something that’s likely to help. And that’s, we try to develop new ideas of things that could help, but certainly when you see somebody in the clinic, you want to steer them towards something that you think is worth the time and the energy, as opposed to something that may be a distraction or could even be harmful.

Frampton Gwynette: Sure, sure. Are there even scientific teams out there right now who are doing work that you’re particularly excited about in terms of breakthrough treatments or breakthrough even generic research?

Jeremy Veenstra-VanderWeele: So there are currently studies going on in very severe neurodevelopmental syndromes, some of which are related to autism, some of which are sort of next door neighbors. So for instance, Rett syndrome, where there’s been work over the last 20 or so years showing the gene that’s responsible, showing how that gene affects brain function. And now there’s work showing that you can sort of turn the gene around, that you can actually cause the gene to be functional again in a mouse and now work. That’s just moving into human studies to try to do just that. And that’s incredible. Now that’s in Rett syndrome. You wouldn’t do that in a person who is, they’re doing it in mice right now. You wouldn’t do it in a person who’s in college. You wouldn’t do it in somebody who is doing well in their life, who’s, I don’t need the treatment. But in Rett syndrome, people actually have a decline over time. They lose motor function. They lose the ability to speak if they developed that-

Frampton Gwynette: It’s really hard, the family’s desperate for treatment.

Jeremy Veenstra-VanderWeele: Yep. Yep. And these are people who end up dying of their disorders. So it’s a reasonable place to start. And that’s just, it’s incredible. It almost feels like science fiction to say that you’ll be able to reverse genetic changes, mutations that happened and maybe lead to dramatic improvements in people’s lives. What we don’t know is how straight forward that’s going to be in a human. We don’t know whether there are going to be side effects that we don’t anticipate. There’s a lot to be done, but it’s just incredibly exciting to think about.

Frampton Gwynette: Really is. We’re finally getting that pay off after 20 or 30 years of generic research research, we’re starting to see those first swings.

Jeremy Veenstra-VanderWeele: Yeah. I remember when I first was in the lab, probably 23 years ago, I asked my mentor at the time, “So, what if we find something what difference is that going to make?” And it was shortly after, I guess about 1994 was when the first fragile X mouse model was described. And he said, “Well, we’ll then study it in a mouse, understand what it’s happening in a brain and have a potential treatment.” And now we actually have treatment studies in fragile X syndrome based on the mouse. We don’t yet have anything that changes somebody’s life in a dramatic way. But we’re at that point. In some ways it feels like, “Oh my goodness, it’s 20 something years later, why aren’t we there yet?” But in another sense, five, 10 years ago, there wasn’t a genetic test that we recommended for every child with autism. Now there is. And increasingly we’re going from that 10% you find with a micro-array to 20% that you find with exome sequencing, which is huge. But where we aren’t yet is treatments based on genetics that actually impact people’s lives.

Frampton Gwynette: So it sounds like reason to be optimistic and keep working hard looking for those treatments. That’s fantastic. So I’m just going to transition now, because a few years ago, I mean time flies, but not too long ago you moved from Vanderbilt up to New York City. And how’s that move been for you?

Jeremy Veenstra-VanderWeele: So I liked living in Nashville. I liked Vanderbilt quite a lot. I love New York City, New York City’s a really exciting place to be. It’s really dynamic. And the place I moved to, Columbia University in New York State Psychiatric Institute is just bigger and there’s just incredible neuroscience happening, incredible clinicians, incredible education. So we have lots of people who are interested in learning both how to study and how to treat folks who are struggling with autism or related difficulties. So it’s a really exciting place to be. But it was exciting to be in Nashville and Vanderbilt as well.

Frampton Gwynette: So what’s the toughest thing about being a New Yorker?

Jeremy Veenstra-VanderWeele: The month of August, although I generally didn’t love the month of August in Nashville.

Frampton Gwynette: Foggy. [crosstalk 00:15:04].

Jeremy Veenstra-VanderWeele: Yeah, the concrete holds the heat and so you walk outside and you feel like the heat is just radiating up at you. Yeah.

Frampton Gwynette: Yeah, that is. Okay, cool. And then I was going to ask next, I’m just looking at maybe your patients or other autism self-advocates that are known, what is it about individuals with autism that you admire?

Jeremy Veenstra-VanderWeele: That’s a good question. So a lot of things, but to me it sort of comes down to most people with autism are pretty straightforward, so I don’t really, there are interactions that you have with people where you’re feeling manipulated or you’re feeling like somebody’s playing you and people with autism tend to be really straightforward. I generally find quite likable in a way that that isn’t always driven the general population. And I also like working with families and their kids together. I’m a child psychiatrist, so I mostly work with younger folks. So I guess I would say that, saying what you like about people with autism in general is a little bit like saying what do you like about people?

Jeremy Veenstra-VanderWeele: Because people with autism are very different from one another from somebody who is able to say, “I don’t need a psychiatrist. Thank you very much,” to somebody who may not be able to speak for themselves. So it’s a broad range and I find that I like people on both sides of that or all sides of that range.

Frampton Gwynette: That’s cool. And I knew that you were part of a couple of presentations here, and so, can you tell us a little bit about the work you’re presenting here?

Jeremy Veenstra-VanderWeele: So this is actually a fairly quiet meeting for me. So I was part of a session this morning that was about outcome measures in clinical trials in autism. So those outcome measures are a real challenge for us because we’ve never really had a treatment that we know helps core symptoms, either social communication or repetitive behavior in autism. We’ve got behavioral treatments that do that. But not in a way that you put in front of the food and drug administration as a potential drug. So it’s really challenging to know what works and it’s an exciting challenge because we’re at the point where we have ideas for what might be helpful, but it’s also frustrating, because we would like to know more, we’d like to have better tools.

Frampton Gwynette: And it’s so tough to measure, blood sugar you can measure easily, autism is a lot of kind of challenges that you’re trying to quantify. People are doing it.

Jeremy Veenstra-VanderWeele: Yeah, no, that’s exactly right. And how do you quantify somebody’s interaction with another person? We’re all so different. You may, it’s hard to pick up changes over the course of a study.

Frampton Gwynette: Yeah, good. Just a couple more questions, and this may seem like a little bit of curve ball, but we are based in Charleston, South Carolina, which as you may know is a college football hotbed, which is the same way in Tennessee where you work. But if pressed-

Jeremy Veenstra-VanderWeele: Well, Vanderbilt wasn’t very good, although we did go to a football game from time to time. Yeah.

Frampton Gwynette: It’s fun. As you see, it’s good football. But if pressed, we ask all of our guests is, if you had to pick between Carolina or Clemson, what would you say?

Jeremy Veenstra-VanderWeele: Is Clemson in South Carolina?

Frampton Gwynette: Yes it is.

Jeremy Veenstra-VanderWeele: Didn’t they? They won the national championship last year. So that I guess I, I don’t know. I’m sure I’ll vote for Clemson. Go with the winner.

Frampton Gwynette: This is the first time we’ve asked this question in an international setting. So thank you for offering to do it. And then the next question is, we’ll wrap it up here, but as you know, the Autism News Network is a program where we’re offering social opportunities and vocational opportunities for adults with autism. And it’s funny because when we started it, I thought the best approach would be to have, this is going to sound silly, but me on camera talking about autism and all I know about autism, which is close to that. But what I found was the goal really is where they’re on camera developing stories and sharing stories that are important to them. But would you like to see the autism news network focused on any particular area will cover in any particular stories, or any advice you have?

Jeremy Veenstra-VanderWeele: Yeah, but that’s a good question. To me, maybe I’ll give the same advice that I usually give to students in general, which is focus on what you care about, because that’s usually the thing that will work out well. When people try to focus on something that they don’t themselves find very interesting, it doesn’t go very well. And so I would say that for whoever is shaping the segment, whether it’s the producer or the reporter focusing on something that they’re really passionately interested in and then using as sort of an editorial sounding board, somebody who’s a little less interested, right? So your goal is to get somebody interested and excited about something that you like. I think that that would probably work, but I’m sure that you have better ideas that I do.

Frampton Gwynette: No, no, that sounds wonderful. We really appreciate the time.

Jeremy Veenstra-VanderWeele: Oh, certainly.

Frampton Gwynette: We’ve been with Dr. Jeremy Veenstra-VanderWeele and coming at you from Montreal, Quebec, Canada. Jeremy, thanks so much.

Jeremy Veenstra-VanderWeele: Super. Thanks Frampton.