So about ten minutes ago, Insel sends out a link to a new blog he has written entitled:
So my immediate thought is... "Well apparently we have gotten his attention, and he is going to now have to tip his had to environmental causes to stay in the game. Let's see what he has to say."
Well he certainly starts out asking the right questions:
Increasing prevalence suggests environmental factors like chemicals and microbes changing over the past decade, whereas genes change over generations. Why is anyone looking for genetic causes when there is such a rapid increase in prevalence? Shouldn’t every research dollar be invested in finding the environmental culprit rather than searching for rare gene variants?
Imagine my shock when he then fails to answer those burning questions and, who would have guessed it, he spent the whole piece promoting GENETICS! The thing actually should have been entitled, "The New Genetics of Autism - Why Genes Matter - Seriously They Do - Please Don't Fire Me - I'm Really Smart."
He flat out says that at most 20% of cases are "genetic," and that seems to be his justification for not answering "Hell, YES!" to that last question on shouldn't research dollars be going to environmental causes!
He does say of course the obligatory, "environment plays a role," but even freely admits that genetic research will NOT find environmental causes! But hey... lets keep pouring our time, money and children down that bottomless pit called 'Genetic Research on Autism.'
This what I see when I read this horrid essay:
I have been entrusted with finding the causes and cures of autism for the last six years, but instead, autism rates have more than doubled on my watch. I freely admit that more than 80% of autism is environmental, and less than 20% can be attributed to genetic causes, but I have decided to ignore the environmental factors in autism that could, if found and quickly addressed to prevent exposures, could end the autism epidemic in the next two or three birth cohorts.
Instead, I am going to continue to pour hundreds of millions of tax payer dollars into genetic studies that have not yet prevented one case of autism, nor lead to one medical treatment for autism, into this dead end, just in case we find something really cool that might help us call some kinds of autism one thing and some kinds of autism something else. They still won't tell us what we can do to prevent autism in kids of parents who have these genes, and it might even be that the genes are not even the parents genes, but genes that get broken in the sperm cells cause they are poisoned or microwaved or whatever in daddy's drawers before conception, but still... how cool is it to find different genes and stuff!
My earnest hope has been that you wouldn't notice that I have already wasted 700 million dollars doing nothing and issuing reports that say nothing except, "send me more money to figure this out, I am totally gonna fix this, I swear... but it is just so hard!", but as a hundred thousand or so of you in the autism community have just called for me to be fired, I am guessing that is out the door. So now I am really just hoping that I can get away with using the word "environmental" in a title on my blog and you will be fooled into thinking I am taking the autism epidemic seriously.
Failing that, I can only hope that you have decided that I am an ineffectual douchbag who does not have the competence to figure this out, because if that does not fly, it will be super apparent to anyone to takes a hard look at me that I am a corrupt bastard trying to preserve my brother Dick's interest and those of the Administrations big donors. Also HHS... please don't notice that we are actually a vaccine maker too, and get cash payments from the people you THINK are making the vaccines, like Merck, cause we hold patents on the shots that we recommend you buy from them. (Have you heard about my brother Dick? Yyou see he brought a vaccine to market, sold the company to Wyeth, then went to work trying to cure diabetes. See what he did there... make a product that causes autoimmune disorders, then make a bundle treating autoimmune disorders! Money coming and going... genius really. He is the smarter brother, I will give him that.)
Also about HHS... please don't notice that we are actually a vaccine maker too, and get cash payments from the people you THINK are making the vaccines, like Merck, cause we hold patents on the shots that we recommend you buy from them. Yes I work for NIH and yes NIH holds the Gardasil patent, and yes NIH gets a check for every Gardasil shot you buy, and no we never disclose that, but I swear... vaccines are not a problem. It genes. Really.
In closing, please notice what a pleasant smile I have. Autism parents are good people.
Full text of the blog piece:
April 04, 2012
The New Genetics of Autism – Why Environment MattersLast week’s autism news was about prevalence. The CDC reported a 78 percent increase in autism prevalence since 2002. This week’s autism news is about genetics—three papers in Nature describe new genes associated with autism. For many people, these two stories seem contradictory or, at best, unrelated. Increasing prevalence suggests environmental factors like chemicals and microbes changing over the past decade, whereas genes change over generations. Why is anyone looking for genetic causes when there is such a rapid increase in prevalence? Shouldn’t every research dollar be invested in finding the environmental culprit rather than searching for rare gene variants?The simple answer is that some autism is genetic. Autism, like schizophrenia and mood disorders, includes many syndromes. Indeed, we should probably speak of the “autisms.” Some of these autisms are single gene disorders, such as Fragile X, tuberous sclerosis, and Rett syndrome. While these rare genetic disorders account for less than 5 percent of children within the autism spectrum, children with any of these disorders are at high risk for autism, roughly a 30-fold higher risk than the general population and higher than any of the other known risk factors. Recent genomics research has discovered that many children diagnosed within the autism spectrum have other genetic mutations that have not yet been designated as named syndromes. Each of these mutations is rare, but in aggregate they may account for 10 - 20 percent or more of what we have been calling the autisms.1The new papers published today in Nature use an approach called whole exome sequencing, mapping every base of DNA across the exome—the 1.5 percent of the genome known to code for protein. The three research groups are members of the Autism Sequencing Consortium (ASC), an international team of autism genetics researchers. All three look for de novo or spontaneous mutations, changes in DNA sequence that are not found in either parent. Recent sequencing studies in the general population have demonstrated that each of us diverges genomically from our parents — the process of reproduction introduces variation even beyond the random mixture of the genomes we inherit from mom and dad. People with autism and schizophrenia are far more likely to have large de novo copy number variants, sometimes a million bases of DNA that are abnormally duplicated or deleted and not found in either parent.These new papers go beyond the previous discovery of de novo copy number variants to identify de novo single base changes associated with autism. This is tough sailing because there are so many of these changes in all of us and most of these single base changes have no impact. These studies tried to improve the odds of success by focusing on individuals from families with no one else affected (these are called “simplex” families), and sometimes comparing the individual with autism to a sibling without autism. The results are intriguing.There is no breakthrough or single gene that is a major new cause of autism. But the role of genetics becomes even more evident when these single base changes are considered. For instance, an individual with autism is nearly 6-fold more likely to have a functional variant in genes expressed in the brain. Sanders et al. estimate as many as 14 percent of affected individuals have such a risk variant.2 This 14 percent is in addition to the 10–20 percent with a large copy number variant or identified genetic syndrome. O’Roak et al. find that 39 percent of these variants are related to a specific biochemical pathway, important for brain signaling.3 And Neale et al., while cautioning that the net effect of all of these changes still leave much of the risk for autism unexplained, note the roles of a few specific genes as genuine risk factors.4Stepping back from this flood of genomic information, what is most important? First, these reports along with previous publications confirm that genetic risk is both complex and substantial. While individual genes appear to confer limited risk, the aggregate effect of spontaneous coding mutations across the genome is now estimated to increase the risk of autism by 5–20-fold.4 Complex genetics does not mean modest effects.Second, the kinds of small and large genetic changes associated with autism are common in everyone. Risk is conferred not by the size of the mutation or the number of mutations (we all have many) but by the location. Increasingly, we see that interference with the genes involved in development of synapses confer risk; a similar change upstream or downstream does not.A third point takes us back to the questions we started with. It is important to understand that de novo mutations may represent environmental effects. In other words, environmental factors can cause changes in our DNA that can raise the risk for autism and other disorders. One of these papers reports that spontaneous changes are four times more likely to show up in paternally inherited DNA and are correlated with paternal age.2 The father’s germline, his sperm cells, turn over throughout the lifespan. Presumably, with advancing paternal age, there are a greater number of spontaneous mutations and a greater likelihood that some of these will affect risk genes. Environmental factors and exposures can cause sperm cells to develop mutations that are not found in the father’s somatic, or body cell, DNA, but these new, spontaneous mutations can be passed to the next generation, raising the risk for developing autism. In the initial report of the relationship between autism and paternal age, boys with autism were 6-fold more likely to have a father in his 40s vs his 20s. In girls with autism, this difference went up to 17-fold.5 Paternal age has, of course, increased in the past few decades. This does not explain the increasing prevalence of autism, but it may contribute.Is autism genetic or environmental? These new studies suggest it can be both. Genetics will not identify the environmental factors, but it may reveal some of the many syndromes within the autism spectrum (as in other neurodevelopmental disorders), it can define risk (as in other medical disorders), and it should yield clues to the biology of autism (revealing potential targets for new treatments). These three new papers on spontaneous mutations are an important milestone in a long journey. In parallel we need to find environmental factors, recognizing that there will be many causes for the autisms and many roads to find them.Finally, an unavoidable insight from these new papers is that autism even when genetic may be spontaneous and not inherited in the sense that one or both parents carry some reduced form of the syndrome. Perhaps this insight will finally reduce the “blame the parents” legacy perpetuated for too long in the absence of scientific evidence.
References1Geschwind DH. Genetics of autism spectrum disorders. Trends Cogn Sci. 2011 Sep;15(9):409-16. Epub 2011 Aug 18. PubMed PMID: 21855394.1
2Sanders SJ, Murtha MT, Gupta AR, Murdoch JD, Raubeson MJ, Willsey AJ, Ercan-Sencicek AG, DiLullo NM, Parikshak NN, Stein JL, Walker MF, Ober GT, Teran NA, Song Y, El-Fishawy P, Murtha RC, Choi M, Overton JD, Bjornson RD, Carriero NJ, Meyer KA, Bilguvar K, Mane SM, Sestan N, Lifton RP, Günel M, Roeder K, Geschwind DH, Devlin B, State MW. De novo mutations revealed by whole-exome sequencing are strongly associated with autism. April 5, 2012. Nature.
3O’Roak BJ, Vives L, Girirajan S, Karakoc E, Krumm N, Coe BP, Levy R, Ko A, Lee C, Smith JD, Turner EH, Stanaway IB, Vernot B, Malig M, Baker C, Reilly B, Akey JM, Borenstein E, Rieder MJ, Nickerson DA, Bernier R, Shendure J, Eichler EE. Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations. Nature. April 5, 2012.
4Neale BM, Kou Y, Liu L, Ma’ayan A, Samocha KE, Sabo A, Lin CF, Stevens C, Wang LS, Makarov V, Polak P, Yoon S, Maguire J, Crawford EL, Campbell NG, Geller ET, Valladares O, Schafer C, Liu H, Zhao T, Cai G, Lihm J, Dannenfelser R, Jabado O, Peralta Z, Nagaswamy U, Muzny D, Reid JG, Newsham I, Wu Y, Lewis L, Han Y, Voight BF, Lim E, Rossin E, Kirby A, Flannick J, Fromer M, Shair K, Fennell T, Garimella K, Banks E, Poplin R, Gabriel S, DePristo M, Wimbish JR, Boone BE, Levy SE, Betancur C, Sunyaev S, Boerwinkle E, Buxbaum JD, Cook EH, Devlin B, Gibbs RA, Roeder K, Schellenberg GD, Sutcliffe JS, Daly MJ. Patterns and rates of exonic de novo mutations in autism spectrum disorders. Nature. April 5, 2012.
5Reichenberg A, Gross R, Weiser M, Bresnahan M, Silverman J, Harlap S, Rabinowitz J, Shulman C, Malaspina D, Lubin G, Knobler HY, Davidson M, Susser E. Advancing paternal age and autism. Arch Gen Psychiatry. 2006 Sep;63(9):1026-32. PubMed PMID: 16953005.