Changing the future of autism with open science: “What we know about autism is not enough; MSSNG is the search for the answers" 
 
 Today, Autism Speaks launches “MSSNG,” an awareness campaign to support the development of the world’s largest database of sequenced genomic information on people with autism spectrum disorder (ASD) and their family members. Autism Speaks is collaborating with Google to store sequenced data from MSSNG on the Google Cloud Platform, providing an open resource for scientists worldwide to access and share autism research. 
 
 Previously known as The Autism Speaks Ten Thousand Genomes Program (AUT10K), MSSNG is a significant milestone in advancing genomic research of autism and could lead to breakthroughs into the causes, subtypes and better diagnosis and treatment for the disorder. 
 
 MSSNG aims to sequence and analyze the whole genomes of 10,000 individuals in families affected by autism – an unprecedented undertaking that will provide the global autism research community with a platform to answer some of the most vexing questions about the disorder. 
 
 Pronounced “missing,” the name has vowels deliberately omitted to represent the missing pieces of the autism puzzle. It is symbolic of the missing information about autism that the project is designed to find. The campaign will enable discoveries that promise advances in medical care and quality-of-life for those struggling with autism and their families. 
 
 MSSNG will also serve as a platform to raise awareness of the beauty inside all those affected by autism. Visual components for the campaign include striking images of crystalized DNA that tell the story of who we are as individuals. (See video below.) 
 
 The campaign will be supported online via a social movement to raise awareness and donations. It encourages supporters to remove vowels from their Twitter display name by going to their profile, clicking “Edit” then “Name” and removing vowels. Autism Speaks invites its supporters to post the following: We’re missing a lot of information on autism. Support @AutismSpeaks project #MSSNG by removing letters from your name: http://mss.ng. 
 
 "Millions of people living with autism today need answers,” says Autism Speaks President Liz Feld. "The MSSNG project is the search for those answers, and we're going to find them. The best research minds in the world are going to mine this database of DNA so we can uncover and understand the various subtypes of autism. Then we can get to work developing customized treatments and therapies so we can improve the quality of life for so many people who need help." 
 
 The MSSNG database will be an open resource to support autism research. However, the massive amount of data being collected creates unique challenges for storage, analysis and access. In June 2014, Autism Speaks announced its collaboration with Google to store MSSNG’s sequenced genomic data on the Google Cloud Platform. This platform provides the engineering innovation needed to address the storage and analysis challenges, while providing a portal for open source access by qualified researchers around the world. 
 
 World-renowned geneticist Stephen Scherer serves as director of MSSNG. A world pioneer in genetics and genomics, Dr. Scherer established the Database of Genomic Variants, the world’s first and most-used database of copy number variants (CNVs). Physicians and medical geneticists use this vital tool in making hundreds of thousands of medical diagnoses. 
 
 The MSSNG program has already sequenced more than 1,000 genomes with close to 2,000 additional samples in the sequencing queue. Results from the first 100 genomes were published in the American Journal of Human Genetics, in July 2013. The landmark study advanced understanding of autism subtypes and provided several families with information useful in guiding diagnosis and treatment. 
 
 The MSSNG program is expected to uncover many subtypes of autism and lead to individualized treatments. For more information, visit www.autismspeaks.org/mssng. 
 
 The crystallization of human DNA. Autism Speaks’ MSSNG campaign is using these beautiful images to illustrate the inherent beauty in all those affected by autism. “What we know about autism is not enough: MSSNG is the search for the answers.” 
 
 See more of today’s MSSNG media coverage at WashingtonPost.com and WIRED.com. ||||| Perhaps you saw the headline. God knows, it was eye catching enough: “Autism’s Unexpected Link to Cancer Gene.” (Update, 8/12/13, 5 pm ET: the headline has now been changed to read, "Autism's Unexpected Link," although the URL retains the original. Update 9/2/13: Now the hed's been updated to "Autism's unexpected link to cancer genes.") 
 
 That headline and the utterly confusing story that follows it both fail to emphasize two very important clarifications: First, the gene in question isn’t just a “cancer gene.” It’s a gene that regulates the cell cycle, and changes in these genes can and do have effects that aren’t confined to cancer. Calling it a “cancer” gene in this context is inflammatory, at best. 
 
 Second, and more important, the autism in question, according to all of the research involving this gene and other similar genes, is part of a syndrome of traits that includes a head circumference that is either significantly small (microcephaly) or significantly larger (macrocephaly) than typical. It comes with clinical signs other than autism, and that’s important, particularly for parents looking at their children after reading this article and thinking, “Cancer?” 
 
 Gina Kolata, in this story for the New York Times, does not focus on these features of a syndrome that can include autism and traces to a gene, PTEN. PTEN contains the code for a protein that’s responsible for keeping cells from dividing out of control. Because that’s its day job, it’s known as a tumor suppressor gene. Mutations in the code can result in a protein that doesn’t work. Obviously, if something that suppresses tumors doesn’t work, the result can be… tumors. 
 
 But dysregulation of cell division or the proteins involved in it isn’t confined to producing only cancers. For example, Alzheimer’s disease might trace to faults of uncontrolled cell division. Another disorder rooted in dysfunctional tumor repressor proteins is tuberous sclerosis, in which benign but sometimes severely interfering tumors grow in various tissues, affecting many systems of the body. These tumors are not cancer. 
 
 In other words, it’s not exactly news that disrupting the work of tumor suppressing proteins can result in non-cancer effects on many body systems, including the brain. And it’s not news that sometimes, these effects on the brain translate behaviorally as the disorder we call autism. In fact, about half of people with tuberous sclerosis also have autism. 
 
 That’s something researchers have known for at least a decade and a half, if not longer. Indeed, science writer Virginia Hughes wrote about this identical subject almost exactly five years ago. Yet Kolata, writing under the banner headline “Autism’s unexpected link to cancer gene,” describes this is a “newly discovered link” while turning stomach-churning phrases such as “parallels between autism and cancer.” Here’s the thing: Genes are codes, like words are. Like words, what arises from that genetic code can have many different chemical meanings in a cell. Sharing a word of origin between them doesn’t mean that they have “parallels” otherwise, and cancer and autism do not share clinical similarities. As an example, I give you “hack.” It can have two meanings with the same root but very different implications. Depending on your time frame, it can mean a cab for hire in the 19th century, or it can mean a writer whose work is so poor or poorly researched, the result is an article that looks as though it had been attacked by an axe. 
 
 Another thing about such words is that a slight change in the code can result in some very different outcomes. For example, a simple letter change in “hack” can give us the word “tack,” as in, let’s take a different tack here and get down to brass tacks. 
 
 Kolata mentions tuberous sclerosis, but her real focus as the “new discovery” is the tumor suppressor PTEN. The thing is, for almost a decade, researchers have linked the PTEN tumor suppressor and autistic behaviors. It is not new, and dozens of publications have addressed it. 
 
 And the article fails to highlight a key fact. The work it focuses on, from Evan Eichler’s lab at the University of Washington, is available here (it was published online last year) and mentions one feature repeatedly, as does the literature on PTEN and autism. Autistic people with PTEN mutations tend also to have the condition of macrocephaly. That’s not just having a big head. It’s having a head that is a size that is pathologically well out of the range of typical head circumference. It’s part of a syndrome associated with PTEN, and autism is present in about one out of ten cases. Indeed, it’s so well known that according to one recent review of the link between PTEN and autism, children who present with both autism and macrocephaly should be tested for PTEN mutations. 
 
 In addition to leaving out this key feature of the PTEN-related syndrome, Kolata also conflates the concepts of increased risk and cause. She repeatedly uses the term “cause” in describing the link between autism and PTEN, starting with her assertion in the lead paragraph that “Some people with autism have mutated cancer or tumor genes that apparently caused their brain disorder.” In fairness, some researchers do the same, even though an actual causative mechanism remains to be established. 
 
 Yet only 1 in 10 people with PTEN mutations also have autism, about 10 times the rate of the general population. That means carrying a PTEN mutation can be a risk, not necessarily a cause, and the autism manifestations in people with PTEN mutations might be secondary to PTEN’s immediate effects. Indeed, a recent review of autism and PTEN concluded that changes in this gene might work in concert with other susceptibility gene variants for autism to result in the behaviors we refer to as autism spectrum disorder. And one possible angle of interest this article completely omitted in pursuit of an eyeball-catching 'cancer link' is the role of PTEN in mitochondrial function and the potential involvement of mitochondrial dysfunction in a subset of autism cases. 
 
 For parents and autistic people who might have read the headline and the article and added “cancer” to their list of worries, here’s another bit of information the article omitted: The mutations in the PTEN gene that are linked to autism tend to be different from those for PTEN-associated cancer. Indeed, they affect the resulting protein in different, less extreme ways, and research indicates no correlation between PTEN-associated cancers and PTEN-associated ASDs, according to these authors (sorry, paywalled). 
 
 Nine paragraphs in, the New York Times article quotes one equivocator, Harvard geneticist Steven McCarroll, as noting that children with the PTEN mutations not only have autism but also have a brain with many other issues, “failing in many ways,” and that autism could be the result of a general brain “malfunction.” According to the article, McCarroll says, 
 
 The fact that autism is one of the many neurological problems that arise in these patients doesn’t necessarily tell us anything penetrating about the social and language deficits that are specific to autism. 
 
 Kolata eventually mentions that the PTEN link would apply to “only a small proportion of people with autism,” but doesn’t specifically state that said proportion is about 1% of autistic people. Because of the inflammatory headline and opening paragraph and the assertions of “cause” and “parallel,” I have no doubt, from long experience in the autism community, that this article will have two effects: It will conflate autism and cancer yet again in people’s minds and lead parents of autistic children to worry that now, they must also angst about a predisposition to cancer, and it will anger autistic advocates and those who care about them because of its careless comparison of autism and a fatal disease. Autistic people and their families deserve more care than this, and readers of the New York Times deserve careful, accurate science writing placed in an appropriate context. 
 
 [Update: Paul Raeburn, writing for the Knight Science Journalism Tracker at MIT, spoke with researcher Evan Eichler, whom Kolata's article quoted, and gives Eichler's reaction to the NYT article here.]
– To learn more about the genetics behind autism, researchers are planning to sequence the genomes of thousands of people—and they've enlisted a partner who knows a thing or two about sifting through scads of data. Using its Genomics tool, Google will host on its servers and index the huge volumes of data involved; a human genome can fill up 100 gigabytes of space, and researchers will investigate those of 10,000 individuals on the autism spectrum as well as their relatives, Wired reports. "We realized that some of our biggest biology problems were really big data problems," says a top scientist with advocacy group Autism Speaks. "We believe that the clues to understanding autism lie in that genome," he continues. "We’d like to leverage the same kind of technology and approach to searching the Internet every day to search into the genome for these missing answers." The technology will allow researchers to track down particular genome sections that interest them, looking closely at areas where subjects have common variations, Wired notes. The partnership between Google and Autism Speaks will offer "an open resource for scientists worldwide to access and share autism research," the group says on its site. (A chemical found in broccoli may help cut down on symptoms in people with autism.)