Wow, amazing interest in the article by Moises Velasquez-Manoff in yesterday’s Sunday NYT (link to it is found on my Facebook page). The title is provocative and the style is very flashy and not at all scholarly or scientific. He does not back up his claims with footnotes or cite the evidence for the claims in article – there are no data, tables or figures to support the case. But, this is a newspaper Opinion Piece, not a science writer’s blog. A newspaper would not put a scholarly article in the Opinion page of its Sunday edition! In fact, last fall I sent around a carefully worded, respectable piece, that made many of the same points as this article does, and it was rejected by all major newspapers I sent it to. I conclude that it takes a different style to get published in this type of venue, and Moises is good at this.
Style aside, the crucial importance of this article is that it gets the message of immune involvement in autism out there in the public eye. This is what I’m trying to do with this lowly blog, and with my book. Moises reached far more folks in one day than I have I’m sure. It’s the most emailed article of the week in the NYT.
But how accurate are his claims? Moises says in his third sentence (!) that “At least a subset of autism – perhaps one-third, and very likely more – looks like a type of inflammatory disease. and it begins in the womb.” The work of Tony Persico, which I highlighted in a July 18 post here, estimates that an immune-related cluster of symptoms is present in about 18% of his autism patient population. Carlos Pardo found evidence of an immune activated state (activated microglia and astrocytes, and strikingly elevated cytokines) in the brains of most of his postmortem autism cases. Several of the Pardo findings (see my 11/19/11 post for update, and my book for full story) have been reproduced by others at UCSD, UCDavis and here at Caltech. In addition, many studies have demonstrated immune abnormalities in the blood in autism (as we have shown in our mouse model of the maternal immune activation risk factor for autism). Moreover, as I’ve pointed out here before (and in the book in detail), there are several reliable studies showing that a high proportion of ASD kids have gastrointestinal problems, many of which could be related to inflammation, such as “leaky gut”, wherein the intestinal barrier allows large molecules to leak out into the circulation. So, I fully agree with Moises that there is a very significant proportion of ASD patients with immune-related problems. Whether it is a third or more than that, is open for debate and further research.
Does this immune dysregulated state “begin in the womb”? First, as Moises points out, there is strong evidence from a huge population of ASD cases in Denmark connecting maternal infection with elevated risk for ASD in the offspring. This is now replicated in a similar, large study in Sweden that was reported at the IMFAR meeting this spring. Additional evidence of this is provided by studies showing markers of inflammation in the amniotic fluid and maternal serum in cases where the offspring turned out to have ASD. A new paper from the Danish group now shows that newborns who go on to develop ASD have elevated serum cytokines. Evidence from our maternal immune activation mouse model is consistent with many of these findings, and our results also provide evidence that the immune dysregulation seen in the blood of adult offspring does begin in the embryo (see my 7/17/12 post here).
Moises then makes a connection between the rise in autism diagnosis, autoimmune disease in the mother, and the hygiene hypothesis, as I did in my book. It seems logical to me to connect the documented rise in autoimmune disease seen in industrialized countries – please see the figure in my June 27, 2012 post that illustrates the truly remarkable parallel between the rise in a number of autoimmune diseases and the fall of a number of infectious diseases. Since a number of studies have shown that autoimmune disease in the mother raises the risk for ASD in the offspring, it again seems logical to connect this with the rise in ASD diagnosis. This is still an hypothesis, of course, but it is based on logic.
In the last part of his article, Moises goes on to extend the hygiene hypothesis to parasites (worms in the GI tract) and notes that a clinical study will begin soon in NYC testing whether giving the parasite Trichuris suis to adult autism subjects will ameliorate their behavioral symptoms. As I’ve pointed out in previous posts here, the idea is that helminth worms can have anti-inflammatory effects, and they are, in an evolutionary sense, a “natural” treatment. The particular parasites to be used have been found to be seemingly harmless in prior human studies. I sincerely hope, however, that the patients to be entered into this study belong to the subset of autism cases that are “immune-related”, otherwise this treatment will likely not correct anything. It will also be important to test for the efficacy of this treatment in reducing immune abnormalities in the blood of the patients. It would also be very revealing to determine if the abnormal, possibly “bad” microbiota (clostridia, sutterela) that should be present in these preselected patients are replaced by “good” (lactobacillae) bacteria (see my post of Jan 19, 2012 on this). [Note: I looked up this trial on ClinicalTrials.gov and the protocol does not mention selecting patients who have immune dysregulation or GI problems, nor does it mention assaying immune parameters before and after treatment]
The one point Moises makes that I am unfamiliar with is about the lack of autism in Cambodia. I’ll have to try to track down a reference for that. Note: Moises just sent me the ref for this – it is a essentially a case report from a doc on Cambodia who is familiar with autism diagnosis and says that he sees remarkably few cases at his center. [Note: here is an update on ASD in developing countries in an article from Iran]
Importantly, Moises says that he is putting together an annotated version of his article that will go on line and show where he got his info from. Good!
Infectious Behavior 
Your book just arrived via amazon. Did you say NYT rejected your submission? I am canceling my subscription. My son on the spectrum, has never had a cold or run a fever in his life. He is so sick, that he does not get sick. How is that for irony.
This is exciting stuff. Keep up
The good work.
Thanks for the post (and the various other interesting posts). It appears that quite a few people have taken the NYTimes opinion piece to task based on several points made during the article. I wonder if you would be minded to resubmit your piece to the NYTimes either in its original form or revised as a sort of scientific ‘add-on’ to the continuing soap opera of immunity and autism?
Yes, complaints that he did not support his points with evidence and that he overstated the case. I hope my post speaks to these issues. RE sending an article to NYT again, newspapers have a phobia about repeated articles on the same theme.
I agree with Paul Whiteley, if you would take the advice of a total stranger, by all means resubmit! The squeaky wheel gets the grease, as we say in my family. Plus, phobia or no, they will need scientific back-up on this one. Mr. Manoff’s article was not just any article, it’s being facebooked, twittered and emailed everywhere. In any case, thank you for your work on the subject. Mr. Manoff has written a fascinating and field changing opinion piece because of the work of researchers like you.
I’m told that Moises is putting together an annotated version of his article to back up his claims. Thx for your support Amy.
I am a mother of a child with autism. I have several auto-immune disorders. And had a UTI while pregnant with my son who has autism as well as an awful cold/fever while we were living in the UK. Very interesting stuff. If it “proves” to be true–I wonder what the impact is on the severity of the autism. My son is moderate to lower and, sadly, does not make the greatest progress at school.
I am sorry to hear about you son Kathleen. It is possible that your UTI had an effect on the outcome, as studies have linked a higher risk for ASD with maternal bacterial and viral infections. Of course, it is impossible to give a definitive answer in any individual case, as the epidemiology involves studies of hundreds to thousands of subjects in order to achieve statistical significance. Good luck with you boy, PHP
I just found your blog and look forward to reading your book. Dr. Patterson. Do you know the work of the Foundation for Psychocultural Resaerch? I would be very interested in a study of Cesarean-section babies vs. vaginal canal delivered babies to show a possible outcome of a rise in both autism and GI-tract diseases (with perhaps an ancillary study on developed v. undeveloped countries’ C-section rates). According to the theory by my co-author, Jessica Black, ND., in the womb, the fetus is not exposed to any microflora. She says, “a baby begins developing its massive microbial milieu the minute it passes through the birth canal.” (Chapter 4: Childhood Development and Gastrointestinal Disorders. “Living With Crohn’s & Colitis: A Comprehensive Naturopathic Guide for Complete Digestive Wellness”) When I read Kathleen’s post I was so sorry to hear about her UTI infection as a possible link to her son’s autism. I expect there will be a lot of interest and research in the gut-brain field, in part due to Moises’s article, and to your excellent work at MIT.
I, too, looked for supported claims in the Moises article, but I thought it was great, and look forward to the interactive edition! I have tried to get my story and book into the NYTimes, to no avail…I think I have a unique patient perspective, and maybe the doctors will start to listen to me—and it may help more people.
Again, thanks for your great work!
Thx Dede. Yes, I know that foundation and gave a talk there at UCLA a couple of years ago. Yes, the baby picks up most of its gut microbiome from its passage thru the birth canal. If it is delivered by C-section, it gets its bacteria from the skin of people how handle it. Interestingly, there are several papers reporting that, compared to normal births, the risk of autism is somewhat higher in kids delivered by C-section. Cheers, PHP
Dr. Patterson – thank you for this blog. I was wondering if you could help me understand something from the NY Times article. Reading the article, it sounds to me (clearly I am not well-versed in any of this) that a woman suffering from allergies during her pregnancy may increase the risk of autism. I am 13 weeks pregnant with my 2nd child who, although early, appears to be a boy. I currently live in Texas but grew up in the Northeast. I often have 2 week stints of pretty bad seasonal allergies. I do not take any medicine when the allergies flare up – rather just suffer through those couple/few weeks. Well, since I have been living here (for the past 4 years) it seems that they come almost quarterly. I have not had any allergies since I have been pregnant but am guessing that it may only be a matter of time. When pregnant, I don’t take any medicine – no matter the “safe” rating. Would you share with me your opinion as to how best to approach the pending seasonal allergies when they arrive so as best to protect my child from the possible autism link? If it matters, I am 39 and will definitely deliver via c-section as my first child was breach and my doctor does not believe in VBAC.
Marie, Yes, statistics show that women with allergies or asthma have a higher risk of autism in their offspring. However, the risk is still low. That is, if this immune condition doubles the risk, and the risk is normally 1%, then such women have a 2% risk for having a child with that condition. Those are averages derived from many hundred or thousands of cases. Thus, the numbers do not apply directly to any individual woman. Much would depend on the woman’s and the fetus’ genetic background, for instance. In sum, altho the relevance of immune status is real, the risk is still low, on average. Cheers, PHP
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Thank you for your work! I am a woman with Crohn’s and a daughter with autism. I’m also a librarian so I have searched Crohn’s and autism together as the paths seem too similar to me to ignore. A co-worker alerted me to Moises Velasquez-Manoff’s NYT article last month. Immediately we ordered the book for the library. I picked it up last night and went online to read more about it. His blog lead me to your blog. I can’t say enough how excited I am to read about your research.
One thing I would like to see happen: women with autoimmune disease should not be routinely given large doses of antibiotics during labor just because they test positive for strep B. I wish I had been smarter at the time at fought that one. You don’t know how good it feels to say that to someone who is in a position to make a difference.