Why Are Autism Rates Steadily Rising?
Stefania Sterling was just 21 when she had her son, Charlie. She was young and healthy, with no genetic issues apparent in either her or her husband's family, so she expected Charlie to be typical.
"It is surprising that the prevalence of a significant disorder like autism has risen so consistently over a relatively brief period."
It wasn't until she went to a Mommy and Me music class when he was one, and she saw all the other one-year-olds walking, that she realized how different her son was. He could barely crawl, didn't speak, and made no eye contact. By the time he was three, he was diagnosed as being on the lower functioning end of the autism spectrum.
She isn't sure why it happened – and researchers, too, are still trying to understand the basis of the complex condition. Studies suggest that genes can act together with influences from the environment to affect development in ways that lead to Autism Spectrum Disorder (ASD). But rates of ASD are rising dramatically, making the need to figure out why it's happening all the more urgent.
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Indeed, the CDC's latest autism report, released last week, which uses 2016 data, found that the prevalence of ASD in four-year-old children was one in 64 children, or 15.6 affected children per 1,000. That's more than the 14.1 rate they found in 2014, for the 11 states included in the study. New Jersey, as in years past, was the highest, with 25.3 per 1,000, compared to Missouri, which had just 8.8 per 1,000.
The rate for eight-year-olds had risen as well. Researchers found the ASD prevalence nationwide was 18.5 per 1,000, or one in 54, about 10 percent higher than the 16.8 rate found in 2014. New Jersey, again, was the highest, at one in 32 kids, compared to Colorado, which had the lowest rate, at one in 76 kids. For New Jersey, that's a 175 percent rise from the baseline number taken in 2000, when the state had just one in 101 kids.
"It is surprising that the prevalence of a significant disorder like autism has risen so consistently over a relatively brief period," said Walter Zahorodny, an associate professor of pediatrics at Rutgers New Jersey Medical School, who was involved in collecting the data.
The study echoed the findings of a surprising 2011 study in South Korea that found 1 in every 38 students had ASD. That was the the first comprehensive study of autism prevalence using a total population sample: A team of investigators from the U.S., South Korea, and Canada looked at 55,000 children ages 7 to 12 living in a community in South Korea and found that 2.64 percent of them had some level of autism.
Searching for Answers
Scientists can't put their finger on why rates are rising. Some say it's better diagnosis. That is, it's not that more people have autism. It's that we're better at detecting it. Others attribute it to changes in the diagnostic criteria. Specifically, the May 2013 update of the Diagnostic and Statistical Manual of Mental Disorders-5 -- the standard classification of mental disorders -- removed the communication deficit from the autism definition, which made more children fall under that category. Cynical observers believe physicians and therapists are handing out the diagnosis more freely to allow access to services available only to children with autism, but that are also effective for other children.
Alycia Halladay, chief science officer for the Autism Science Foundation in New York, said she wishes there were just one answer, but there's not. While she believes the rising ASD numbers are due in part to factors like better diagnosis and a change in the definition, she does not believe that accounts for the entire rise in prevalence. As for the high numbers in New Jersey, she said the state has always had a higher prevalence of autism compared to other states. It is also one of the few states that does a good job at recording cases of autism in its educational records, meaning that children in New Jersey are more likely to be counted compared to kids in other states.
"Not every state is as good as New Jersey," she said. "That accounts for some of the difference compared to elsewhere, but we don't know if it's all of the difference in prevalence, or most of it, or what."
"What we do know is that vaccinations do not cause autism."
There is simply no defined proven reason for these increases, said Scott Badesch, outgoing president and CEO of the Autism Society of America.
"There are suggestions that it is based on better diagnosis, but there are also suggestions that the incidence of autism is in fact increasing due to reasons that have yet been determined," he said, adding, "What we do know is that vaccinations do not cause autism."
Zahorodny, the pediatrics professor, believes something is going on beyond better detection or evolving definitions.
"Changes in awareness and shifts in how children are identified or diagnosed are relevant, but they only take you so far in accounting for an increase of this magnitude," he said. "We don't know what is driving the surge in autism recorded by the ADDM Network and others."
He suggested that the increase in prevalence could be due to non-genetic environmental triggers or risk factors we do not yet know about, citing possibilities including parental age, prematurity, low birth rate, multiplicity, breech presentation, or C-section delivery. It may not be one, but rather several factors combined, he said.
"Increases in ASD prevalence have affected the whole population, so the triggers or risks must be very widely dispersed across all strata," he added.
There are studies that find new risk factors for ASD almost on a daily basis, said Idan Menashe, assistant professor in the Department of Health at Ben-Gurion University of the Negev, the fastest growing research university in Israel.
"There are plenty of studies that find new genetic variants (and new genes)," he said. In addition, various prenatal and perinatal risk factors are associated with a risk of ASD. He cited a study his university conducted last year on the relationship between C-section births and ASD, which found that exposure to general anesthesia may explain the association.
Whatever the cause, health practitioners are seeing the consequences in real time.
"People say rates are higher because of the changes in the diagnostic criteria," said Dr. Roseann Capanna-Hodge, a psychologist in Ridgefield, CT. "And they say it's easier for children to get identified. I say that's not the truth and that I've been doing this for 30 years, and that even 10 years ago, I did not see the level of autism that I do see today."
Sure, we're better at detecting autism, she added, but the detection improvements have largely occurred at the low- to mid- level part of the spectrum. The higher rates of autism are occurring at the more severe end, in her experience.
A Polarizing Theory
Among the more controversial risk factors scientists are exploring is the role environmental toxins may play in the development of autism. Some scientists, doctors and mental health experts suspect that toxins like heavy metals, pesticides, chemicals, or pollution may interrupt the way genes are expressed or the way endocrine systems function, manifesting in symptoms of autism. But others firmly resist such claims, at least until more evidence comes forth. To date, studies have been mixed and many have been more associative than causative.
"Today, scientists are still trying to figure out whether there are other environmental changes that can explain this rise, but studies of this question didn't provide any conclusive answer," said Menashe, who also serves as the scientific director of the National Autism Research Center at BGU.
"It's not everything that makes Charlie. He's just like any other kid."
That inconclusiveness has not dissuaded some doctors from taking the perspective that toxins do play a role. "Autism rates are rising because there is a mismatch between our genes and our environment," said Julia Getzelman, a pediatrician in San Francisco. "The majority of our evolution didn't include the kinds of toxic hits we are experiencing. The planet has changed drastically in just the last 75 years –- it has become more and more polluted with tens of thousands of unregulated chemicals being used by industry that are having effects on our most vulnerable."
She cites BPA, an industrial chemical that has been used since the 1960s to make certain plastics and resins. A large body of research, she says, has shown its impact on human health and the endocrine system. BPA binds to our own hormone receptors, so it may negatively impact the thyroid and brain. A study in 2015 was the first to identify a link between BPA and some children with autism, but the relationship was associative, not causative. Meanwhile, the Food and Drug Administration maintains that BPA is safe at the current levels occurring in food, based on its ongoing review of the available scientific evidence.
Michael Mooney, President of St. Louis-based Delta Genesis, a non-profit organization that treats children struggling with neurodevelopmental delays like autism, suspects a strong role for epigenetics, which refers to changes in how genes are expressed as a result of environmental influences, lifestyle behaviors, age, or disease states.
He believes some children are genetically predisposed to the disorder, and some unknown influence or combination of influences pushes them over the edge, triggering epigenetic changes that result in symptoms of autism.
For Stefania Sterling, it doesn't really matter how or why she had an autistic child. That's only one part of Charlie.
"It's not everything that makes Charlie," she said. "He's just like any other kid. He comes with happy moments. He comes with sad moments. Just like my other three kids."
This Brain Doc Has a “Repulsive” Idea to Make Football Safer
What do football superstars Tom Brady, Drew Brees, Philip Rivers, and Adrian Peterson all have in common? Last year they wore helmets that provided the poorest protection against concussions in all the NFL.
"You're only as protected as well as the worst helmet that's out there."
A Dangerous Policy
Football helmets are rated on a one-star to five-star system based on how well they do the job of protecting the player. The league has allowed players to use their favorites, regardless of the star rating.
The Oxford-trained neuroscientist Ray Colello conducted a serious analysis of just how much the protection can vary between each level of star rating. Colello and his team of graduate students sifted through two seasons of game video to identify which players were wearing what helmets. There was "a really good correlation with position, but the correlation is much more significant based on age."
"The average player in the NFL is 26.6 years old, but the average age of a player wearing a one-star helmet is 34. And for anyone who knows football, that's ancient," the brain doc says. "Then for our two-star helmet, it's 32; and for a three-star helmet it's 29." Players were sticking with the helmets they were familiar with in college, despite the fact that equipment had improved considerably in recent years.
"You're only as protected as well as the worst helmet that's out there," Colello explains. Offering an auto analogy, he says, "It's like, if you run into the back of a Pinto, even if you are in a five-star Mercedes, that gas tank may still explode and you are still going to die."
It's one thing for a player to take a risk at scrambling his own brain; it's another matter to put a teammate or opponent at needless risk. Colello published his analysis early last year and the NFL moved quickly to ban the worst performing helmets, starting next season.
Some of the 14 players using the soon-to-be-banned helmets, like Drew Brees and Philip Rivers, made the switch to a five-star helmet at the start of training camp and stayed with it. Adrian Peterson wore a one-star helmet throughout the season.
Tom Brady tried but just couldn't get comfortable with a new bonnet and, after losing a few games, switched back to his old one in the middle of the season; he says he's going to ask the league to "grandfather in" his old helmet so he can continue to use it.
As for Colello, he's only just getting started. The brain doc has a much bigger vision for the future of football safety. He wants to prevent concussions from even occurring in the first place by creating an innovative new helmet that's unlike anything the league has ever seen.
Oxford-trained neuroscientist Ray Colello is on a mission to make football safer.
(Photo credit: VCU public affairs)
"A Force Field" of Protection
His inspiration was serendipitous; he was at home watching a football game on TV when Denver Bronco's receiver Wes Welker was hit, lay flat on the field with a concussion, and was carted off. As a commercial flickered on the screen, he ambled into the kitchen for another beer. "What those guys need is a force field protecting them," he thought to himself.
Like so many households, the refrigerator door was festooned with magnets holding his kids' school work in place. And in that eureka moment the idea popped into his head: "Maybe the repulsive force of magnets can put a break on an impact before it even occurs." Colello has spent the last few years trying to turn his concept into reality.
Newton's laws of physics – mass and speed – play out graphically in a concussion. The sudden stop of a helmet-to-helmet collision can shake the brain back and forth inside the skull like beans in a maraca. Dried beans stand up to the impact, making their distinctive musical sound; living brain tissue is much softer and not nearly so percussive. The resulting damage is a concussion.
The risk of that occurring is greater than you might think. Researchers using accelerometers inside helmets have determined that a typical college football player experiences about 600 helmet-to-helmet contacts during a season of practice and games. Each hit generates a split second peak g-force of 20 to 150 within the helmet and the odds of one causing a concussion increase sharply over 100 gs of force.
By comparison, astronauts typically experience a maximum sustained 3gs during lift off and most humans will black out around 9gs, which is why fighter pilots wear special pressure suits to counter the effects.
"It stretches the time line of impact quite dramatically. In fact in most instances, it doesn't even hit."
The NFL's fastest player, Chris Johnson, can run 19.3 mph. A collision at that speed "produces 120gs worth of force," Colello explains. "But if you can extend that time of impact by just 5 milliseconds (from 12 to 17msec) you'll shift that g-force down to 84. There is a very good chance that he won't suffer a concussion."
The neuroscientist dived into learning all he could about the physics magnets. It turns out that the most powerful commercially available magnet is an alloy made of neodymium, iron, and boron. The elements can be mixed and glued together in any shape and then an electric current is run through to make it magnetic; the direction of the current establishes the north-south poles.
A 1-pound neodymium magnet can repulse 600 times its own weight, even though the magnetic field extends less than an inch. That means it can push back a magnet inside another helmet but not affect the brain.
Crash Testing the Magnets
Colello couldn't wait to see if his idea panned out. With blessing from his wife to use their credit card, he purchased some neodymium magnets and jury-rigged experiments at home.
The reinforced plastics used in football helmets don't affect the magnetic field. And the small magnets stopped weights on gym equipment that were dropped from various heights. "It stretches the time line of impact quite dramatically. In fact in most instances, it doesn't even hit," says Colello. "We are dramatically shifting the curve" of impact.
Virginia Commonwealth University stepped in with a $50,000 innovation grant to support the next research steps. The professor ordered magnets custom-designed to fit the curvature of space inside the front and sides of existing football helmets. That makes it impossible to install them the wrong way, and ensures the magnets' poles will always repel and not attract. It adds about a pound and a half to the weight of the helmet.
a) The brain in a helmet. b) Placing the magnet. c) Measuring the impact of a helmet-to-helmet collision. d) How magnets reduce the force of impact.
(Courtesy Ray Colello)
Colello rented crash test dummy heads crammed with accelerometers and found that the magnets performed equally well at slowing collisions when fixed to a pendulum in a test that approximated a helmet and head hitting a similarly equipped helmet. It impressively reduced the force of contact.
The NFL was looking for outside-the-box thinking to prevent concussions. It was intrigued by Colello's approach and two years ago invited him to submit materials for review. To be fair to all entrants, the league proposed to subject all entries to the same standard crush test to see how well each performed in lessening impact. The only trouble was, Colello's approach was designed to avoid collisions, not lessen their impact. The test wouldn't have been a valid evaluation and he withdrew from consideration.
But Colello's work caught the attention of Stefan Duma, an engineering professor at Virginia Tech who developed the five-star rating system for football helmets.
"In theory it makes sense to use [the magnets] to slow down or reduce acceleration, that's logical," says Duma. He believes current helmet technology is nearing "the end of the physics barrier; you can only absorb so much energy in so much space," so the field is ripe for new approaches to improve helmet technology.
However, one of Duma's concerns is whether magnets "are feasible from a weight standpoint." Most helmets today weigh between two and four pounds, and a sufficiently powerful magnet might add too much weight. One possibility is using an electromagnet, which potentially could be lighter and more powerful, particularly if the power supply could be carried lower in the body, say in the shoulder pads.
Colello says his lab tests are promising enough that the concept needs to be tried out on the playing field. "We need to make enough helmets for two teams to play each other in a regulation-style game and measure the impact forces that are generated on each, and see if there is a significant reduction." He is waiting to hear from the National Institutes of Health on a grant proposal to take that next step toward dramatically reducing the risk of concussions in the NFL.
Just five milliseconds could do it.
Genetically Sequencing Healthy Babies Yielded Surprising Results
Today in Melrose, Massachusetts, Cora Stetson is the picture of good health, a bubbly precocious 2-year-old. But Cora has two separate mutations in the gene that produces a critical enzyme called biotinidase and her body produces only 40 percent of the normal levels of that enzyme.
In the last few years, the dream of predicting and preventing diseases through genomics, starting in childhood, is finally within reach.
That's enough to pass conventional newborn (heelstick) screening, but may not be enough for normal brain development, putting baby Cora at risk for seizures and cognitive impairment. But thanks to an experimental study in which Cora's DNA was sequenced after birth, this condition was discovered and she is being treated with a safe and inexpensive vitamin supplement.
Stories like these are beginning to emerge from the BabySeq Project, the first clinical trial in the world to systematically sequence healthy newborn infants. This trial was led by my research group with funding from the National Institutes of Health. While still controversial, it is pointing the way to a future in which adults, or even newborns, can receive comprehensive genetic analysis in order to determine their risk of future disease and enable opportunities to prevent them.
Some believe that medicine is still not ready for genomic population screening, but others feel it is long overdue. After all, the sequencing of the Human Genome Project was completed in 2003, and with this milestone, it became feasible to sequence and interpret the genome of any human being. The costs have come down dramatically since then; an entire human genome can now be sequenced for about $800, although the costs of bioinformatic and medical interpretation can add another $200 to $2000 more, depending upon the number of genes interrogated and the sophistication of the interpretive effort.
Two-year-old Cora Stetson, whose DNA sequencing after birth identified a potentially dangerous genetic mutation in time for her to receive preventive treatment.
(Photo courtesy of Robert Green)
The ability to sequence the human genome yielded extraordinary benefits in scientific discovery, disease diagnosis, and targeted cancer treatment. But the ability of genomes to detect health risks in advance, to actually predict the medical future of an individual, has been mired in controversy and slow to manifest. In particular, the oft-cited vision that healthy infants could be genetically tested at birth in order to predict and prevent the diseases they would encounter, has proven to be far tougher to implement than anyone anticipated.
But in the last few years, the dream of predicting and preventing diseases through genomics, starting in childhood, is finally within reach. Why did it take so long? And what remains to be done?
Great Expectations
Part of the problem was the unrealistic expectations that had been building for years in advance of the genomic science itself. For example, the 1997 film Gattaca portrayed a near future in which the lifetime risk of disease was readily predicted the moment an infant is born. In the fanfare that accompanied the completion of the Human Genome Project, the notion of predicting and preventing future disease in an individual became a powerful meme that was used to inspire investment and public support for genomic research long before the tools were in place to make it happen.
Another part of the problem was the success of state-mandated newborn screening programs that began in the 1960's with biochemical tests of the "heel-stick" for babies with metabolic disorders. These programs have worked beautifully, costing only a few dollars per baby and saving thousands of infants from death and severe cognitive impairment. It seemed only logical that a new technology like genome sequencing would add power and promise to such programs. But instead of embracing the notion of newborn sequencing, newborn screening laboratories have thus far rejected the entire idea as too expensive, too ambiguous, and too threatening to the comfortable constituency that they had built within the public health framework.
"What can you find when you look as deeply as possible into the medical genomes of healthy individuals?"
Creating the Evidence Base for Preventive Genomics
Despite a number of obstacles, there are researchers who are exploring how to achieve the original vision of genomic testing as a tool for disease prediction and prevention. For example, in our NIH-funded MedSeq Project, we were the first to ask the question: "What can you find when you look as deeply as possible into the medical genomes of healthy individuals?"
Most people do not understand that genetic information comes in four separate categories: 1) dominant mutations putting the individual at risk for rare conditions like familial forms of heart disease or cancer, (2) recessive mutations putting the individual's children at risk for rare conditions like cystic fibrosis or PKU, (3) variants across the genome that can be tallied to construct polygenic risk scores for common conditions like heart disease or type 2 diabetes, and (4) variants that can influence drug metabolism or predict drug side effects such as the muscle pain that occasionally occurs with statin use.
The technological and analytical challenges of our study were formidable, because we decided to systematically interrogate over 5000 disease-associated genes and report results in all four categories of genetic information directly to the primary care physicians for each of our volunteers. We enrolled 200 adults and found that everyone who was sequenced had medically relevant polygenic and pharmacogenomic results, over 90 percent carried recessive mutations that could have been important to reproduction, and an extraordinary 14.5 percent carried dominant mutations for rare genetic conditions.
A few years later we launched the BabySeq Project. In this study, we restricted the number of genes to include only those with child/adolescent onset that could benefit medically from early warning, and even so, we found 9.4 percent carried dominant mutations for rare conditions.
At first, our interpretation around the high proportion of apparently healthy individuals with dominant mutations for rare genetic conditions was simple – that these conditions had lower "penetrance" than anticipated; in other words, only a small proportion of those who carried the dominant mutation would get the disease. If this interpretation were to hold, then genetic risk information might be far less useful than we had hoped.
Suddenly the information available in the genome of even an apparently healthy individual is looking more robust, and the prospect of preventive genomics is looking feasible.
But then we circled back with each adult or infant in order to examine and test them for any possible features of the rare disease in question. When we did this, we were surprised to see that in over a quarter of those carrying such mutations, there were already subtle signs of the disease in question that had not even been suspected! Now our interpretation was different. We now believe that genetic risk may be responsible for subclinical disease in a much higher proportion of people than has ever been suspected!
Meanwhile, colleagues of ours have been demonstrating that detailed analysis of polygenic risk scores can identify individuals at high risk for common conditions like heart disease. So adding up the medically relevant results in any given genome, we start to see that you can learn your risks for a rare monogenic condition, a common polygenic condition, a bad effect from a drug you might take in the future, or for having a child with a devastating recessive condition. Suddenly the information available in the genome of even an apparently healthy individual is looking more robust, and the prospect of preventive genomics is looking feasible.
Preventive Genomics Arrives in Clinical Medicine
There is still considerable evidence to gather before we can recommend genomic screening for the entire population. For example, it is important to make sure that families who learn about such risks do not suffer harms or waste resources from excessive medical attention. And many doctors don't yet have guidance on how to use such information with their patients. But our research is convincing many people that preventive genomics is coming and that it will save lives.
In fact, we recently launched a Preventive Genomics Clinic at Brigham and Women's Hospital where information-seeking adults can obtain predictive genomic testing with the highest quality interpretation and medical context, and be coached over time in light of their disease risks toward a healthier outcome. Insurance doesn't yet cover such testing, so patients must pay out of pocket for now, but they can choose from a menu of genetic screening tests, all of which are more comprehensive than consumer-facing products. Genetic counseling is available but optional. So far, this service is for adults only, but sequencing for children will surely follow soon.
As the costs of sequencing and other Omics technologies continue to decline, we will see both responsible and irresponsible marketing of genetic testing, and we will need to guard against unscientific claims. But at the same time, we must be far more imaginative and fast moving in mainstream medicine than we have been to date in order to claim the emerging benefits of preventive genomics where it is now clear that suffering can be averted, and lives can be saved. The future has arrived if we are bold enough to grasp it.
Funding and Disclosures:
Dr. Green's research is supported by the National Institutes of Health, the Department of Defense and through donations to The Franca Sozzani Fund for Preventive Genomics. Dr. Green receives compensation for advising the following companies: AIA, Applied Therapeutics, Helix, Ohana, OptraHealth, Prudential, Verily and Veritas; and is co-founder and advisor to Genome Medical, Inc, a technology and services company providing genetics expertise to patients, providers, employers and care systems.