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."
Not Vaccinating Your Kids Endangers Public Health
[Editor's Note: This opinion essay is in response to our current Big Question, which we posed to experts with different viewpoints: "Where should society draw the line between requiring vaccinations for children and allowing parental freedom of choice?"]
Society has a right and at times an obligation to require children to be vaccinated. Vaccines are one of the most effective medical and public health interventions. They save lives and prevent suffering. The vast majority of parents in the United States fully vaccinate their children according to the recommended immunization schedule. These parents are making decisions so that the interests of their children and the interest of society are the same. There are no ethical tensions.
"Measles is only a plane ride away from American children."
A strong scientific basis supports the recommended immunization schedule. The benefits of recommended vaccines are much bigger than the risks. However, a very small proportion of parents are ideologically opposed to vaccines. A slightly larger minority of parents do not believe that all of the recommended vaccines are in their child's best interests.
Forgoing vaccinations creates risk to the child of contracting diseases. It also creates risk to communities and vulnerable groups of people who cannot be vaccinated because of their age or health status.
For example, many vaccines are not able to be given to newborns, such as the measles vaccine which is recommended at 12-15 months of age, leaving young children vulnerable. Many diseases are particularly dangerous for young children. There are also some children who can't be vaccinated, such as pediatric cancer patients who are undergoing chemotherapy or radiation treatment. These children are at increased risk of serous complication or death.
Then there are people who are vaccinated but remain susceptible to disease because no vaccine is 100% effective. In the case of measles, two doses of vaccines protect 97% of people, leaving 3% still susceptible even after being fully vaccinated. All of these groups of people – too young, not eligible, and vaccinated but still susceptible – are dependent on almost everyone else to get vaccinated in order for them to be protected.
Sadly, even though measles has been largely controlled because most people get the very safe and very effective vaccine, we are now seeing dangerous new outbreaks because some parents are refusing vaccines for their children, especially in Europe. Children have died. Measles is only a plane ride away from American children.
There have been repeated measles outbreaks in the United States – such as the Disneyland outbreak and six outbreaks already this year - because of communities where too many parents refuse the vaccine and measles is brought over, often from Europe.
The public health benefits cannot be emphasized enough: Vaccines are not just about protecting your child. Vaccines protect other children and the entire community. Vaccine-preventable diseases (with the exception of tetanus) are spread from person to person. The decision of a parent to not vaccinate their child can endanger other children and vulnerable people.
As a vaccine safety researcher for 20 years, I believe that the community benefit of vaccination can provide justification to limit parental autonomy.
Given these tensions between parental autonomy and the protective value of vaccines, the fundamental question remains: Should society require all children to submit to vaccinations? As a vaccine safety researcher for 20 years, I believe that the community benefit of vaccination can provide justification to limit parental autonomy.
In the United States, we see this balancing act though state requirements for vaccinations to enter school and the varying availability of non-medical exemptions to these laws. Mandatory vaccination in the United States are all state laws. All states require children entering school to receive vaccines and permit medical exemptions. There are a lot of differences between states regarding which vaccines are required, target populations (daycare, school entry, middle school, college), and existence and types of non-medical (religious or philosophical) exemptions that are permitted.
Amid recent measles outbreaks, for instance, California eliminated all non-medical exemptions, making it one of three states that only permit medical exemptions. The existence and enforcement of these school laws reflect broad public support for vaccines to protect the community from disease outbreaks.
I worry about how many kids must suffer, and even die, from diseases like measles until enough is enough. Such tragedies have no place in the modern era. All parents want to do right by their children. All parents deserve autonomy when it comes to decision-making. But when their choices confer serious risks to others, the buck should stop. Our nation would be better off—both medically and ethically—if we did not turn our backs on our most vulnerable individuals.
[Editor's Note: Read the opposite viewpoint here.]
Your Body Has This Astonishing Magical Power
It's vacation time. You and your family visit a country where you've never been and, in fact, your parents or grandparents had never been. You find yourself hiking beside a beautiful lake. It's a gorgeous day. You dive in. You are not alone.
How can your T cells and B cells react to a pathogen they've never seen?
In the water swim parasites, perhaps a parasite called giardia. The invader slips in through your mouth or your urinary tract. This bug is entirely new to you, and there's more. It might be new to everyone you've ever met or come into contact with. The parasite may have evolved in this setting for hundreds of thousands of years so that it's different from any giardia bug you've ever come into contact with before or that thrives in the region where you live.
How can your T cells and B cells react to a pathogen they've never seen, never knew existed, and were never inoculated against, and that you, or your doctors, in all their wisdom, could never have foreseen?
This is the infinity problem.
For years, this was the greatest mystery in immunology.
As I reported An Elegant Defense -- my book about the science of the immune system told through the lives of scientists and medical patients -- I was repeatedly struck by the profundity of this question. It is hard to overstate: how can we survive in a world with such myriad possible threats?
Matt Richtel's new book about the science of the immune system, An Elegant Defense, was published this month.
To further underscore the quandary, the immune system has to neutralize threats without killing the rest of the body. If the immune system could just kill the rest of the body too, the solution to the problem would be easy. Nuke the whole party. That obviously won't work if we are to survive. So the immune system has to be specific to the threat while also leaving most of our organism largely alone.
"God had two options," Dr. Mark Brunvand told me. "He could turn us into ten-foot-tall pimples, or he could give us the power to fight 10 to the 12th power different pathogens." That's a trillion potential bad actors. Why pimples? Pimples are filled with white blood cells, which are rich with immune system cells. In short, you could be a gigantic immune system and nothing else, or you could have some kind of secret power that allowed you to have all the other attributes of a human being—brain, heart, organs, limbs—and still somehow magically be able to fight infinite pathogens.
Dr. Brunvand is a retired Denver oncologist, one of the many medical authorities in the book – from wizened T-cell innovator Dr. Jacques Miller, to the finder of fever, Dr. Charles Dinarello, to his eminence Dr. Anthony Fauci at the National Institutes of Health to newly minted Nobel-Prize winner Jim Allison.
In the case of Dr. Brunvand, the oncologist also is integral to one of the book's narratives, a remarkable story of a friend of mine named Jason. Four years ago, he suffered late, late stage cancer, with 15 pounds of lymphoma growing in his back, and his oncologist put him into hospice. Then Jason became one of the first people ever to take an immunotherapy drug for lymphoma and his tumors disappeared. Through Jason's story, and a handful of other fascinating tales, I showcase how the immune system works.
There are two options for creating such a powerful immune system: we could be pimples or have some other magical power.
Dr. Brunvand had posited to me that there were two options for creating such a powerful and multifaceted immune system: we could be pimples or have some other magical power. You're not a pimple. So what was the ultimate solution?
Over the years, there were a handful of well-intentioned, thoughtful theories, but they strained to account for the inexplicable ability of the body to respond to virtually anything. The theories were complex and suffered from that peculiar side effect of having terrible names—like "side-chain theory" and "template-instructive hypothesis."
This was the background when along came Susumu Tonegawa.
***
Tonegawa was born in 1939, in the Japanese port city of Nagoya, and was reared during the war. Lucky for him, his father was moved around in his job, and so Tonegawa grew up in smaller towns. Otherwise, he might've been in Nagoya on May 14,1944, when the United States sent nearly 550 B-29 bombers to take out key industrial sites there and destroyed huge swaths of the city.
Fifteen years later, in 1959, Tonegawa was a promising student when a professor in Kyoto told him that he should go to the United States because Japan lacked adequate graduate training in molecular biology. A clear, noteworthy phenomenon was taking shape: Immunology and its greatest discoveries were an international affair, discoveries made through cooperation among the world's best brains, national boundaries be damned.
Tonegawa wound up at the University of California at San Diego, at a lab in La Jolla, "the beautiful Southern California town near the Mexican border." There, in multicultural paradise, he received his PhD, studying in the lab of Masaki Hayashi and then moved to the lab of Renato Dulbecco. Dr. Dulbecco was born in Italy, got a medical degree, was recruited to serve in World War II, where he fought the French and then, when Italian fascism collapsed, joined the resistance and fought the Germans. (Eventually, he came to the United States and in 1975 won a Nobel Prize for using molecular biology to show how viruses can lead, in some cases, to tumor creation.)
In 1970, Tonegawa—now armed with a PhD—faced his own immigration conundrum. His visa was set to expire by the end of 1970, and he was forced to leave the country for two years before he could return. He found a job in Switzerland at the Basel Institute for Immunology.
***
Around this time, new technology had emerged that allowed scientists to isolate different segments of an organism's genetic material. The technology allowed segments to be "cut" and then compared to one another. A truism emerged: If a researcher took one organism's genome and cut precisely the same segment over and over again, the resulting fragment of genetic material would match each time.
When you jump in that lake in a foreign land, filled with alien bugs, your body, astonishingly, well might have a defender that recognizes the creature.
This might sound obvious, but it was key to defining the consistency of an organism's genetic structure.
Then Tonegawa found the anomaly.
He was cutting segments of genetic material from within B cells. He began by comparing the segments from immature B cells, meaning, immune system cells that were still developing. When he compared identical segments in these cells, they yielded, predictably, identical fragments of genetic material. That was consistent with all previous knowledge.
But when he compared the segments to identical regions in mature B cells, the result was entirely different. This was new, distinct from any other cell or organism that had been studied. The underlying genetic material had changed.
"It was a big revelation," said Ruslan Medzhitov, a Yale scholar. "What he found, and is currently known, is that the antibody-encoding genes are unlike all other normal genes."
The antibody-encoding genes are unlike all other normal genes.
Yes, I used italics. Your immune system's incredible capabilities begin from a remarkable twist of genetics. When your immune system takes shape, it scrambles itself into millions of different combinations, random mixtures and blends. It is a kind of genetic Big Bang that creates inside your body all kinds of defenders aimed at recognizing all kinds of alien life forms.
So when you jump in that lake in a foreign land, filled with alien bugs, your body, astonishingly, well might have a defender that recognizes the creature.
Light the fireworks and send down the streamers!
As Tonegawa explored further, he discovered a pattern that described the differences between immature B cells and mature ones. Each of them shared key genetic material with one major variance: In the immature B cell, that crucial genetic material was mixed in with, and separated by, a whole array of other genetic material.
As the B cell matured into a fully functioning immune system cell, much of the genetic material dropped out. And not just that: In each maturing B cell, different material dropped out. What had begun as a vast array of genetic coding sharpened into this particular, even unique, strand of genetic material.
***
This is complex stuff. But a pep talk: This section is as deep and important as any in describing the wonder of the human body. Dear reader, please soldier on!
***
Researchers, who, eventually, sought a handy way to define the nature of the genetic change to the material of genes, labeled the key genetic material in an antibody with three initials: V, D, and J.
The letter V stands for variable. The variable part of the genetic material is drawn from hundreds of genes.
D stands for diversity, which is drawn from a pool of dozens of different genes.
And J is drawn from another half dozen genes.
In an immature B cell, the strands of V, D, and J material are in separate groupings, and they are separated by a relatively massive distance. But as the cell matures, a single, random copy of V remains, along with a single each of D and J, and all the other intervening material drops out. As I began to grasp this, it helped me to picture a line of genetic material stretching many miles. Suddenly, three random pieces step forward, and the rest drops away.
The combination of these genetic slices, grouped and condensed into a single cell, creates, by the power of math, trillions of different and virtually unique genetic codes.
In anticipation of threats from the unfathomable, our defenses evolved as infinity machines.
Or if you prefer a different metaphor, the body has randomly made hundreds of millions of different keys, or antibodies. Each fits a lock that is located on a pathogen. Many of these antibodies are combined such that they are alien genetic material—at least to us—and their locks will never surface in the human body. Some may not exist in the entire universe. Our bodies have come stocked with keys to the rarest and even unimaginable locks, forms of evil the world has not yet seen, but someday might. In anticipation of threats from the unfathomable, our defenses evolved as infinity machines.
"The discoveries of Tonegawa explain the genetic background allowing the enormous richness of variation among antibodies," the Nobel Prize committee wrote in its award to him years later, in 1987. "Beyond deeper knowledge of the basic structure of the immune system these discoveries will have importance in improving immunological therapy of different kinds, such as, for instance, the enforcement of vaccinations and inhibition of reactions during transplantation. Another area of importance is those diseases where the immune defense of the individual now attacks the body's own tissues, the so-called autoimmune diseases."
Indeed, these revelations are part of a period of time it would be fair to call the era of immunology, stretching from the middle of the 20th century to the present. During that period, we've come from sheer ignorance of the most basic aspects of the immune system to now being able to tinker under the hood with monoclonal antibodies and other therapies. And we are, in many ways, just at the beginning.