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."
What if people could just survive on sunlight like plants?
The admittedly outlandish question occurred to me after reading about how climate change will exacerbate drought, flooding, and worldwide food shortages. Many of these problems could be eliminated if human photosynthesis were possible. Had anyone ever tried it?
Extreme space travel exists at an ethically unique spot that makes human experimentation much more palatable.
I emailed Sidney Pierce, professor emeritus in the Department of Integrative Biology at the University of South Florida, who studies a type of sea slug, Elysia chlorotica, that eats photosynthetic algae, incorporating the algae's key cell structure into itself. It's still a mystery how exactly a slug can operate the part of the cell that converts sunlight into energy, which requires proteins made by genes to function, but the upshot is that the slugs can (and do) live on sunlight in-between feedings.
Pierce says he gets questions about human photosynthesis a couple of times a year, but it almost certainly wouldn't be worth it to try to develop the process in a human. "A high-metabolic rate, large animal like a human could probably not survive on photosynthesis," he wrote to me in an email. "The main reason is a lack of surface area. They would either have to grow leaves or pull a trailer covered with them."
In short: Plants have already exploited the best tricks for subsisting on photosynthesis, and unless we want to look and act like plants, we won't have much success ourselves. Not that it stopped Pierce from trying to develop human photosynthesis technology anyway: "I even tried to sell it to the Navy back in the day," he told me. "Imagine photosynthetic SEALS."
It turns out, however, that while no one is actively trying to create photosynthetic humans, scientists are considering the ways humans might need to change to adapt to future environments, either here on the rapidly changing Earth or on another planet. Rice University biologist Scott Solomon has written an entire book, Future Humans, in which he explores the environmental pressures that are likely to influence human evolution from this point forward. On Earth, Solomon says, infectious disease will remain a major driver of change. As for Mars, the big two are lower gravity and radiation, the latter of which bombards the Martian surface constantly because the planet has no magnetosphere.
Although he considers this example "pretty out there," Solomon says one possible solution to Mars' magnetic assault could leave humans not photosynthetic green, but orange, thanks to pigments called carotenoids that are responsible for the bright hues of pumpkins and carrots.
"Carotenoids protect against radiation," he says. "Usually only plants and microbes can produce carotenoids, but there's at least one kind of insect, a particular type of aphid, that somehow acquired the gene for making carotenoids from a fungus. We don't exactly know how that happened, but now they're orange... I view that as an example of, hey, maybe humans on Mars will evolve new kinds of pigmentation that will protect us from the radiation there."
We could wait for an orange human-producing genetic variation to occur naturally, or with new gene editing techniques such as CRISPR-Cas9, we could just directly give astronauts genetic advantages such as carotenoid-producing skin. This may not be as far-off as it sounds: Extreme space travel exists at an ethically unique spot that makes human experimentation much more palatable. If an astronaut already plans to subject herself to the enormous experiment of traveling to, and maybe living out her days on, a dangerous and faraway planet, do we have any obligation to provide all the protection we can?
Probably the most vocal person trying to figure out what genetic protections might help astronauts is Cornell geneticist Chris Mason. His lab has outlined a 10-phase, 500-year plan for human survival, starting with the comparatively modest goal of establishing which human genes are not amenable to change and should be marked with a "Do not disturb" sign.
To be clear, Mason is not actually modifying human beings. Instead, his lab has studied genes in radiation-resistant bacteria, such as the Deinococcus genus. They've expressed proteins called DSUP from tardigrades, tiny water bears that can survive in space, in human cells. They've looked into p53, a gene that is overexpressed in elephants and seems to protect them from cancer. They also developed a protocol to work on the NASA twin study comparing astronauts Scott Kelly, who spent a year aboard the International Space Station, and his brother Mark, who did not, to find out what effects space tends to have on genes in the first place.
In a talk he gave in December, Mason reported that 8.7 percent of Scott Kelly's genes—mostly those associated with immune function, DNA repair, and bone formation—did not return to normal after the astronaut had been home for six months. "Some of these space genes, we could engineer them, activate them, have them be hyperactive when you go to space," he said in that same talk. "When we think about having the hubris to go to a faraway planet...it seems like an almost impossible idea….but I really like people and I want us to survive for a long time, and this is the first step on the stairwell to survive out of the solar system."
What is the most important ability we could give our future selves through science?
There are others performing studies to figure out what capabilities we might bestow on the future-proof superhuman, but none of them are quite as extreme as photosynthesis (although all of them are useful). At Harvard, geneticist George Church wants to engineer cells to be resistant to viruses, such as the common cold and HIV. At Columbia, synthetic biologist Harris Wang is addressing self-sufficient humans more directly—trying to spur kidney cells to produce amino acids that are normally only available from diet.
But perhaps Future Humans author Scott Solomon has the most radical idea. I asked him a version of the classic What would be your superhero power? question: What does he see as the most important ability we could give our future selves through science?
"The empathy gene," he said. "The ability to put yourself in someone else's shoes and see the world as they see it. I think it would solve a lot of our problems."
Science's dream of creating perfect custom organs on demand as soon as a patient needs one is still a long way off. But tiny versions are already serving as useful research tools and stepping stones toward full-fledged replacements.
Although organoids cannot yet replace kidneys, they are invaluable tools for research.
The Lowdown
Australian researchers have grown hundreds of mini human kidneys in the past few years. Known as organoids, they function much like their full-grown counterparts, minus a few features due to a lack of blood supply.
Cultivated in a petri dish, these kidneys are still a shadow of their human counterparts. They grow no larger than one-sixth of an inch in diameter; fully developed organs are up to five inches in length. They contain no more than a few dozen nephrons, the kidney's individual blood-filtering unit, whereas a fully-grown kidney has about 1 million nephrons. And the dish variety live for just a few weeks.
An organoid kidney created by the Murdoch Children's Institute in Melbourne, Australia.
Photo Credit: Shahnaz Khan.
But Melissa Little, head of the kidney research laboratory at the Murdoch Children's Institute in Melbourne, says these organoids are invaluable tools for research. Although renal failure is rare in children, more than half of those who suffer from such a disorder inherited it.
The mini kidneys enable scientists to better understand the progression of such disorders because they can be grown with a patient's specific genetic condition.
Mature stem cells can be extracted from a patient's blood sample and then reprogrammed to become like embryonic cells, able to turn into any type of cell in the body. It's akin to walking back the clock so that the cells regain unlimited potential for development. (The Japanese scientist who pioneered this technique was awarded the Nobel Prize in 2012.) These "induced pluripotent stem cells" can then be chemically coaxed to grow into mini kidneys that have the patient's genetic disorder.
"The (genetic) defects are quite clear in the organoids, and they can be monitored in the dish," Little says. To date, her research team has created organoids from 20 different stem cell lines.
Medication regimens can also be tested on the organoids, allowing specific tailoring for each patient. For now, such testing remains restricted to mice, but Little says it eventually will be done on human organoids so that the results can more accurately reflect how a given patient will respond to particular drugs.
Next Steps
Although these organoids cannot yet replace kidneys, Little says they may plug a huge gap in renal care by assisting in developing new treatments for chronic conditions. Currently, most patients with a serious kidney disorder see their options narrow to dialysis or organ transplantation. The former not only requires multiple sessions a week, but takes a huge toll on patient health.
Ten percent of older patients on dialysis die every year in the U.S. Aside from the physical trauma of organ transplantation, finding a suitable donor outside of a family member can be difficult.
"This is just another great example of the potential of pluripotent stem cells."
Meanwhile, the ongoing creation of organoids is supplying Little and her colleagues with enough information to create larger and more functional organs in the future. According to Little, researchers in the Netherlands, for example, have found that implanting organoids in mice leads to the creation of vascular growth, a potential pathway toward creating bigger and better kidneys.
And while Little acknowledges that creating a fully-formed custom organ is the ultimate goal, the mini organs are an important bridge step.
"This is just another great example of the potential of pluripotent stem cells, and I am just passionate to see it do some good."