Participant: My name is Kelli Ann Davis. First of all, I want to show you my son, Miles. He is now almost 15 years old. When he was a baby, I think autism rates were 1 in 5,000, and they are now 1 in 150.
This is my son at two and a half months old. If you look closely, he is trying to mimic speech. Two and a half months old, he was completely fine.
Here he is at 1, and he is completely fine. Here he is at about 3 years old, and if you look in his eyes, you can see he is not really there anymore. Here he is holding his baby sister when he is 6 years old, and you look at him and look how sad he is.
My son is now almost 15 years old. There are a lot of smart people in this room. I’m just a mom, but I am asking for your help to find out the truth about what happened to my son. I believe it had to do with vaccines. I believe mercury had something to do with what happened to my son.
I am here for the truth. That is what I have always wanted to pursue, is the truth. I am just encouraging you all to remember when you are talking, it is about our kids. I have got to tell you that the first time I heard Martha’s talk a couple of years ago at the symposium, I had to go upstairs to the hotel room. I couldn’t even hear her talk because I thought about what has happened to my son and what was going on in his brain.
You are all scientists and you are looking at it from the scientific perspective, and we need that. But there are thousands of parents out there who are heartbroken, and when they hear the descriptions of the brain and the white matter, it is almost too much to take.
So I guess I am just pleading with you all, first of all I want to thank you all for being here, but to please keep that in mind, and remember the kids who aren’t babies anymore. We need the help as quickly as possible.
I just appreciate everybody being here. Thank you so much.
Dr. Leshner: Thank you for that. It underscores the urgency I think we all feel. So thank you.
Mr. Blaxill: It also suggests a tiering around what kind of bio- markers we really care about. They are diagnostic biomarkers that are
final common pathways, they are prognostic biomarkers, they are treatment response biomarkers.
It is easy to have prospective studies and think about the kids that aren’t diagnosed yet or are not affected. The constituency out there needs attention to treatment response. It may not be now, and it may not be specific. It may overlap with all sorts of other things, GI diseases and the language impairment, but there is a prioritization implied in the biomarkers.
Ms. Redwood: I just wanted to make a comment, too. I guess this is moving into the general session, since the parents are talking. What I have heard today is that we are looking at the potential for there being an environmental toxicant that may have caused our children’s disability.
One of the questions I have for the panel is, why aren’t we testing the children? We went into Brick Township and we tested the water and we tested the dirt. We tested everything we could think of, but nobody ever tested the children.
I hear over and over again that mercury is one of those metals that might be causing this. I know for my son, he had over five times EPA’s action level of mercury in his body. I am just wondering why we are not testing the children. If there are multiple toxicants, let’s look at the kids and see what they have. If it is mercury, lead, PCBs, to me that is the study that we are ignoring right now.
So I would like to ask the panel if anybody is looking at that, if anybody is doing urinary porphyrin levels in these children, what are the plans to test the kids?
Dr. Swedo: I have mentioned that the NIMH M.I.N.D. phenome project is the pilot, and that is absolutely child focused, family second, home third. My colleagues can talk about their own studies, but I think your point is very well taken that if you are going to find it, you need to look where they are affected.
That is one of the tensions between the need as Art Beaudet talked about, to find out what the change in incidence is. Those are large-scale expensive studies that have to be done. On the other hand, if this was leukemia or another medical illness where we could look at a cell system and know exactly what was wrong, we wouldn’t spend a lot of time looking at the unaffected to figure out what was happening with those subtypes.
So I think if I were speaking to the urgency, and I am trying to, my plea would be that we do this kind of meeting where everybody is using
the same platform where possible, and drawing on the strengths of each of the different kinds of advances.
Dr. Schwartz: I agree with what Lyn Redwood just said. I would go further by saying that what we should do, we should try to figure out what studies are underway in populations of kids with autism that we can build in the state-of-the-art, but admittedly somewhat limited envi- ronmental measures that could be done on the biospecimens that are available within those studies. There is no reason we shouldn’t do that. If that takes expanding the studies, we just need to look at what it will cost and try to pull those funds together to use in the best way possible to make that information available.
The question I was trying to get at this morning is, what are the cohorts that are ongoing that we could leverage to append these additional studies to that would get at the answers? I think they are not perfect. As Dr. Insel pointed out, we don’t have 39,000 assays, we have 20 assays right now, but maybe 2 or 3 years from now we will have a thousand assays. While we have 200 assays, we may as well make use of them.
Dr. Falk: This has been a very interesting progression from Tom Insel’s comment all the way through to here. It seems to me that a large part of today, the discussion has been around mechanisms and pathways which could be impacted very significantly by environmental agents, but not nearly as much discussion about specific environmental agents. And of course, the pathways themselves may not be fully specific.
In truth, there have been various times where environmental etiologic factors have been identified even before pathways are understood, and only afterward does one go back and understand the pathway.
I guess one conclusion that I do draw from this is that perhaps there ought to be certainly more attention to specific environmental factors, both experimentally as well as in terms of—in the epidemiology we will discuss tomorrow morning, we will have the opportunity to see just what those opportunities are.
But it strikes me that that is an important area that, as I am seeing this all put together, is not fully addressed, perhaps.
Participant: I have a question for Dr. Noble. You talked about thimerosal toxicity at the very end of your talk. Are all of the oligoden- drocyte precursors selectively vulnerable, more so than other types of brain cells?
Dr. Noble: This gets to the issue of when in the life period of a cell
or lineage you see vulnerability. If you wanted to design a system to enable you to study problems like this, you would come up with something like what we now know about the oligodendrocyte lineage, because it has so many advantages to doing this kind of work.
One of them is that myelination occurs at different time periods in different parts of the nervous system. The organism creates cells that intrinsically have different timings. One of the ways that we learn a lot about these problems is to try and understand what controls those timings, and it has turned out to be this intrinsic redox biology.
So when we look at other cell types like embryonic cortical neurons, we find that similar principles apply, but we have to study them at the right stage in order to do this.
I think in terms of this issue of specific toxicants, although I think this is an oversimplification, I have to say that what we keep seeing is that all the cell cares about is, is it oxidized? It doesn’t care who is doing the oxidation. Obviously at other levels there are chemical specificities, but this is what we are seeing.
Can I ask a question? I am trying so hard to understand this area. I think I see an experiment, but I want to ask whether it is a good one, that ties together some of the things that we have heard.
Following on from Dr. Schwartz’s and Ms. Redwood’s important comments about looking at the kids, and what we have heard from the parents about those who have used chelation therapy, is it a good question to ask, if you have a child with autism, and you now screen these other parameters, mercury load, lead load, PCB load, get an environmental toxicant profile on them. Now you do the chelation therapy. Is it the case that the kids in whom that works, are those kids in whom we have higher levels of heavy metals? And is it the case that the parameters that Jill James’s studies normalize, or that auditory brain stem response normalizes? Is that a type of focused question that one can ask to get some traction?
Ms. Bono: That is basically the recovered kids study, which you are talking about. There are DAN doctors throughout America who have kids whom they started working with, 3, 4, 5, 6 years of age, specifically the younger ones are the ones that have the best recovery rate. Some have Jill James’s profiles, these kids have shown methylation problems, oxidative stress. They start chelating, but they also do other things, giving them glutathione, cysteine, all of the things to help with that.
So there are those entry-level treatment biomarkers that the doctors have when they walk in the office. Then they have it tracking as they go along.
Dr. Noble: Can that data be made available to us?
Ms. Bono: The DAN doctors have said that they would be very willing to have data mining go into their offices and pull that type of information.
Ms. Redwood: There is one of the clinicians I saw here a few minutes ago, Nancy O’Hara, who has a very large practice, who might want to share her data.
Participant: I am Nancy O’Hara. I have been working with children with autism for 25 years, first as a teacher, the last 9 years solely with children with autism.
First I want to thank the researchers, because they have given us the information that we need to see why our kids are biochemically sick, and they are, but also to see how we may begin to treat them. They are treatable.
We do have that data. We have the urines, we have the stools, we have the leads pretreatment and posttreatment, in recovered kids and in kids who are not recovered. Believe me, it is not 100 percent, but the data are there. We need help mining that data and taking that data from a large group of clinicians now who have it, but we just don’t have the resources to then pool the data together and use them. But we have them.
There was a lot of talk this morning about inflammation and also this afternoon. They mentioned tonsils on one of the slides.
David Gozal from Kentucky has very interesting literature on the very damaging effect of repetitive hypoxia. He has looked at it in cell culture systems and also in clinical systems, and found that children with learning disorders and also sleep disorders often had tonsil problems, and when they were removed they actually improved considerably. So his repetitive hypoxia paradigm would also fit in with some of the redox type of studies people have been talking about, and I think should be thrown into the big picture.
Dr. Swedo: Before we go down that field though, as a pediatrician I just have to remind folks that tonsils in a 7- to 8-year-old are very different than those in an infant and neonate.
Dr. Leshner: Somebody here was going to respond to the last question.
Dr. Akil: It was a comment about physicians and other people in the
community who have information. Tom Insel and I were talking at lunch about how one might engage physicians in the community, whether it is part of a CME (Continuing Medical Education) or volunteer or whatever, whether we need a medical informatics national project that sits back and thinks about what kind of information is needed to do this in a systematic way, meaning something that one can participate in where the kinds of information that are needed, the kind of diagnostic criteria that are required, the kinds of treatment, the kinds of levels, what assays are approved or not approved, whether we can put something like that together either in a trial in a few centers to begin with before expanding it, and bring information into it and see if there is any way to begin to rely on people who are doing the footwork but feel isolated, and have scientists who are good at data mining or analyzing.
But if you patch it like a patchwork, very pell-mell, it would not be useful. We need to come back to you and say here is the information we need, and then get it from the people in the trenches.
Participant: I agree with you, but you also have to address the urgency which a lot of these parents feel. If you start prospectively and ignore all the data that are already there.
Dr. Akil: You eat it. You eat what you have. You eat the data that you have so far.
Participant: But you have to use that, and they may not be as clean as the data you want to use prospectively. But I think you have to use some of the data you have now to be able to start.
Dr. Swedo: I think that is a fabulous idea. We thought it was such a great idea that we started 3 years ago to develop a national database for autism research, which allows clinicians in the field to become research- ers by providing them with the clinical tools they need to do systematic assessment of their patients.
Our group has been very impressed with the DAN practitioners and are grateful to them for what we are learning from them, are hoping to partner with them even more in the future. But in addition there is another network, the Autism Treatment Network (ATN), which started out on the West Coast and Boston. They now have a dozen sites. They are hoping to get 20 different sites, both academic and clinic community based. They are gathering data from their patients, and if Paul Law is still here, he can speak to the Autism Speaks registry, IAN, Interactive Autism Network, that allows parents to input their data directly about their kids and get instant feedback.
I think we are poised from an informatic standpoint to meet this need of urgency and get the data very quickly, start looking for similarities and differences across this group, and then do more in-depth systematic study as the patterns emerge.
Ms. Bono: I agree with you, all three of those things are very good.
With the DAN doctors, with the huge practices, they need to have more of a systematic approach, where three or four people are on the payroll, and they come in and they mine that data based on whatever criteria they have, and then they move to the next one. These doctors just don’t have the time to go back and try and put it together and give it to you, but it is there.
Dr. Insel: I think one of the great things about the National Database for Autism Research is, it does give you the standardized assessments.
All the tools are there in place, and anyone can use them anywhere. It is totally public access, or will be in September when it goes fully live.
The relevance to this meeting specifically goes back to David Schwartz’s and Lyn Redwood’s point, though. What we don’t have are the large repositories of biological samples on all of the thousands and thousands of kids who have been treated. They may exist someplace. We have a relatively small brain bank, we have small banks of other kinds of samples, but clearly there is a need to do here what was done for childhood leukemias 25 years ago. You find a way to organize, consolidate, and then go from n’s of 10 and 20 and 30 to 2,000, 3,000 or 20,000 or 30,000.
In a complicated area like this, you are going to need those kinds of large n’s to be able to find the subgroups that really will give you ultimately that rigor. We will have the clinical piece. One of the things that would be great for this group to weigh in on is what would be the biological samples, when should they be collected, and what would you want to do with it.
Dr. Leshner: I think that one we should hold for tomorrow.
Dr. Schwartz: And maybe what could we do with them in the absence of an absolutely ideal study. We have probably at NIEHS two or three epidemiology studies that we are funding in autism. I’m sure you probably have a half dozen or a dozen or in aggregate.
There are a number of epidemiological studies in autism that have been done. They are not using the same tools necessarily, they may not have the same diagnostic criteria, but there are areas of overlap that we would agree are critical elements across all of those studies that could
serve to bring those studies together in a biobank that we could then mine for environmental data and genetic data and other data that could push the field forward before the ideal population has been acquired.
Dr. Falk: I am very supportive of these ideas that are coming forward, particularly if the chelation data, for example, are one of the strongest indicators for there being environmental agents. They should be looked at in detail for any group like that that is thinking about environ- mental agents.
But if I may go back to something Mark said before. I want to make sure I understand this correctly. I understood what you were saying to be that there are so many environmental factors which could conceivably affect redox status and pathways, it is almost immaterial to look for the environmental agents? I don’t know whether you quite said that, but maybe that is what I was thinking. You were implying I think that the specific environmental agents might be so numerous that. . . .
Dr. Noble: No, it is the second one. I think that if one wants to test the hypothesis that mercury is the primary causative agent in autism, that that is the wrong hypothesis. If one wants to test the hypothesis that mercury is one of many environmental factors that may contribute to this outcome, that looks like the right hypothesis.
So if we look at what we can look at now, there is a limited number of agents where the sensitivity of analyses are sufficient to enable us to do reasonable studies, the organic materials, PCBs, a few other effects.
That data may turn out to be extraordinarily compelling, particularly because of what we are hearing about the heavy metals and the chelation therapy. At least heavy metals are something that can be analyzed pretty well.
What I am specifically concerned with is that—with all respect and admiration and concern for the parents’ groups and everyone who has been trying to pursue the idea of a specific environment toxicant or a specific vaccination, just from a biological point of view, it doesn’t sound like a great hypothesis. It sounds like these may be pieces, that they happened at a particular time, but they are not going to apply to all the kids.
From the cell’s point of view, I don’t think it matters. Am I oxidized because of an inflammation? Am I oxidized because I got mercury? I don’t care, I’m oxidized, I am in electron deficit. The data that I am hearing just keeps agreeing with that. Even this idea of astrogliosis and the white-matter tracks, when we take these oligodendrocyte progenitors