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."
How Genetic Engineering Could Save the Coral Reefs
Coral reefs are usually relegated to bit player status in television and movies, providing splashes of background color for "Shark Week," "Finding Nemo," and other marine-based entertainment.
In real life, the reefs are an absolutely crucial component of the ecosystem for both oceans and land, rivaling only the rain forests in their biological complexity. They provide shelter and sustenance for up to a quarter of all marine life, oxygenate the water, help protect coastlines from erosion, and support thousands of tourism jobs and businesses.
Genetic engineering could help scientists rebuild the reefs that have been lost, and turn those still alive into a souped-up version that can withstand warmer and even more acidic waters.
But the warming of the world's oceans -- exacerbated by an El Nino event that occurred between 2014 and 2016 -- has been putting the world's reefs under tremendous pressure. Their vibrant colors are being replaced by sepulchral whites and tans.
That's the result of bleaching -- a phenomenon that occurs when the warming waters impact the efficiency of the algae that live within the corals in a symbiotic relationship, providing nourishment via photosynthesis and eliminating waste products. The corals will often "shuffle" their resident algae, reacting in much the same way a landlord does with a non-performing tenant -- evicting them in the hopes of finding a better resident. But when better-performing algae does not appear, the corals become malnourished, eventually becoming deprived of their color and then their lives.
The situation is dire: Two-thirds of Australia's Great Barrier Reef have undergone a bleaching event in recent years, and it's believed up to half of that reef has died.
Moreover, hard corals are the ocean's redwood trees. They take centuries to grow, meaning it could take centuries or more to replace them.
Recent developments in genetic engineering -- and an accidental discovery by researchers at a Florida aquarium -- provide opportunities for scientists to potentially rebuild a large proportion of the reefs that have been lost, and perhaps turn those still alive into a souped-up version that can withstand warmer and even more acidic waters. But many questions have yet to be answered about both the biological impact on the world's oceans, and the ethics of reengineering the linchpin of its ecosystem.
How did we get here?
Coral bleaching was a regular event in the oceans even before they began to warm. As a result, natural selection weeds out the weaker species, says Rachel Levin, an American-born scientist who has performed much of her graduate work in Australia. But the current water warming trend is happening at a much higher rate than it ever has in nature, and neither the coral nor the algae can keep up.
"There is a big concern about giving one variant a huge fitness advantage, have it take over and impact the natural variation that is critical in changing environments."
In a widely-read paper published last year in the journal Frontiers in Microbiology, Levin and her colleagues put forth a fairly radical notion for preserving the coral reefs: Genetically modify their resident algae.
Levin says the focus on algae is a pragmatic decision. Unlike coral, they reproduce extremely rapidly. In theory, a modified version could quickly inhabit and stabilize a reef. About 70 percent of algae -- all part of the genus symbiodinium -- are host generalists. That means they will insert themselves into any species of coral.
In recent years, work on mapping the genomes of both algae and coral has been progressing rapidly. Scientists at Stanford University have recently been manipulating coral genomes using larvae manipulated with the CRISPR/Cas9 technology, although the experimentation has mostly been limited to its fluorescence.
Genetically modifying the coral reefs could seem like a straightforward proposition, but complications are on the horizon. Levin notes that as many as 20 different species of algae can reside within a single coral, so selecting the best ones to tweak may pose a challenge.
"The entire genus is made up of thousands of subspecies, all very genetically distinct variants. There is a huge genetic diversity, and there is a big concern about giving one variant a huge fitness advantage, have it take over and impact the natural variation that is critical in changing environments," Levin says.
Genetic modifications to an algae's thermal tolerance also poses the risk of what Levin calls an "off-target effect." That means a change to one part of the genome could lead to changes in other genes, such as those regulating growth, reproduction, or other elements crucial to its relationship with coral.
Phillip Cleves, a postdoctoral researcher at Stanford who has participated in the CRISPR/Cas9 work, says that future research will focus on studying the genes in coral that regulate the relationship with the algae. But he is so concerned about the ethical issues of genetically manipulating coral to adapt to a changing climate that he declined to discuss it in detail. And most coral species have not yet had their genomes fully mapped, he notes, suggesting that such work could still take years.
An Alternative: Coral Micro-fragmentation
In the meantime, there is another technique for coral preservation led by David Vaughan, senior scientist and program manager at the Mote Marine Laboratory and Aquarium in Sarasota, Florida.
Vaughan's research team has been experimenting in the past decade with hard coral regeneration. Their work had been slow and painstaking, since growing larvae into a coral the size of a quarter takes three years.
The micro-fragmenting process in some ways raises fewer ethical questions than genetically altering the species.
But then, one day in 2006, Vaughan accidentally broke off a tiny piece of coral in the research aquarium. That fragment grew to the size of a quarter in three months, apparently the result of the coral's ability to rapidly regenerate when injured. Further research found that breaking coral in this manner -- even to the size of a single polyp -- led to rapid growth in more than two-dozen species.
Mote is using this process, known as micro-fragmentation, to grow large numbers of coral rapidly, often fusing them on top of larger pieces of dead coral. These coral heads are then planted in the Florida Keys, which has experienced bleaching events over 12 of the last 14 years. The process has sped up almost exponentially; Mote has planted some 36,000 pieces of coral to date, but Vaughan says it's on track to plant 35,000 more pieces this year alone. That sum represents between 20 to 30 acres of restored reef. Mote is on track to plant another 100,000 pieces next year.
This rapid reproduction technique in some ways allows Mote scientists to control for the swift changes in ocean temperature, acidification and other factors. For example, using surviving pieces of coral from areas that have undergone bleaching events means these hardier strains will propagate much faster than nature allows.
Vaughan recently visited the Yucatan Peninsula to work with Mexican researchers who are going to embark on a micro-fragmenting initiative of their own.
The micro-fragmenting process in some ways raises fewer ethical questions than genetically altering the species, although Levin notes that this could also lead to fewer varieties of corals on the ocean floor -- a potential flattening of the colorful backdrops seen in television and movies.
But Vaughan has few qualms, saying this is an ecological imperative. He suggests that micro-fragmentation could serve as a stopgap until genomic technologies further advance.
"We have to use the technology at hand," he says. "This is a lot like responding when a forest burns down. We don't ask questions. We plant trees."
Nancy Cappello was proactive. When she turned 36, she had a baseline mammogram, a standard medical recommendation in the late 1980s and early 1990s as a comparison tool for future screenings. At 40, Cappello started getting them annually.
Her breast surgeon estimated the cancer had been festering for four to five years under the radar of her annual mammograms.
Six weeks after her 11th-consecutive normal mammogram, she was diagnosed with Stage IIIc breast cancer.
A doctor felt a lump while doing a breast exam during her annual physical and a subsequent ultrasound detected cancer that had spread to 13 lymph nodes. That's when Cappello, then 51, learned she had dense breast tissue, making mammography less likely to detect tumors in her breasts.
She also discovered through her own research that she was among the 40 to 50 percent of women with dense breast tissue — almost half the female population — but medical protocol did not require physicians to inform women of their dense tissue status. If she had known, she said, she would have gotten an ultrasound every year in addition to a mammogram that could have detected the cancer much earlier. Cappello said her breast surgeon estimated the cancer had been festering for four to five years under the radar of her annual mammograms.
Although ultrasound as a cancer screening tool has been available for decades, technological advances are helping doctors find more invasive cancers in women with dense breasts, in turn giving women who know their tissue status the opportunity for earlier detection and treatment.
"We know that the gold standard for breast cancer screening is mammography, but in women with dense breast tissue, up to one third of breast cancers can be missed with this modality alone."
Dr. Georgia Giakoumis Spear, chief of the department of breast imaging at NorthShore University HealthSystem in suburban Chicago and assistant professor of radiology at the University of Chicago, has been a leader in developing standards for the use of new ultrasound technology. She is leading a study to develop more specific national guidelines around the use of Automated Whole Breast Tissue Ultrasound (ABUS), a non-invasive procedure in which sound waves are used to scan breast tissue while a patient lies on her back with her arm over her head.
Approved by the Food and Drug Administration in 2012, ABUS provides higher quality 3D images and faster delivery to provide more accurate results than past ultrasound technology. The scan does not involve radiation, and a practitioner can complete the process in 15 to 20 minutes, from patient preparation to image creation. NorthShore has been using ABUS since 2015, Dr. Spear said, and the technology can improve breast cancer detection in women with dense breasts by up to 55 percent.
"We know that the gold standard for breast cancer screening is mammography, but in women with dense breast tissue, up to one third of breast cancers can be missed with this modality alone," Spear says. "And when we supplement screening with ultrasound in this population of women, we have found a large number of cancers by ultrasound that are not visible on the mammogram."
Mammography should still be used as the first step for breast cancer detection, but if an initial mammogram shows that a patient has dense breast tissue, studies encourage discussion of additional screening with ultrasound.
On a mammogram, dense tissue appears white. So do cancerous masses, making them easy to miss.
A radiologist determines tissue density, according to the American College of Radiology's Breast Imaging Reporting and Data System (BI-RADS). "A" and "B" breast density categories designate ratios of mostly fatty, or non-dense tissues, while the "C" and "D" categories designate heterogeneously dense and extremely dense tissue, respectively. Such patients would be classified as having dense tissue. Younger women, women with lower levels of body fat and women undergoing hormone therapy are more likely to have C and D breast density.
On a mammogram, dense tissue appears white. So do cancerous masses, making them easy to miss. Fatty tissue, in comparison, appears black, making tumors easier to spot.
The FDA stated among its policy goals for 2018 that it's placing an improved focus on recognizing technological advances to help "ensure women get the most relevant, up-to-date information about their breast density, which is now recognized as a risk factor for breast cancer." An article in the March 2018 Journal of the American College of Radiology recommended supplemental screening for women with higher-than-average breast cancer risk, placing women with dense breast tissue in that category.
To be sure, some in the medical community are reluctant to push for ultrasounds, saying that a mammogram might be enough even if the woman has dense breast tissue. A patient is advised to discuss the option of ultrasound with her physician and they can decide from there.
Access to such information became political for Cappello after her diagnosis in 2004. She said that as she underwent six surgeries, a mastectomy, chemotherapy, radiation and hormone therapy, she asked doctors why they weren't required to inform women of their dense breast tissue status. Her dissatisfaction with their responses led to the formation of Are You Dense, Inc., an advocacy group aimed to inform women of their medical options while working to pass legislation mandating that women know their tissue status. Other legislation has focused on mandating insurance coverage for breast ultrasounds.
Nancy Cappello.
(Courtesy)
Cappello's work led Connecticut to become the first state to pass an information law in 2009, and 35 states now have similar requirements. Depending on the state, the law could mandate that certain language or information about breast density be included in the patient's mammogram results, or require physicians to tell women about dense tissue if their breast density falls in the BI-RADS categories C and D. Other states might require that patients be given general information about breast density and advice to discuss their options with a physician. (Note: There is a chart on Cappello's website that shows what laws exist – or don't – in each state.)
Through her site and social media, she's connected with other women who've lobbied for laws in their states, including Dr. Spear, who recently testified before legislative committees in Illinois as they considered companion bills. The Illinois legislation is expected to be signed into law this summer.
"There should be no excuses," Cappello says. "Women should have this information. There should be no concealing or hiding of her status."