Can Genetic Testing Help Shed Light on the Autism Epidemic?
Autism cases are still on the rise, and scientists don't know why. In April, the Centers for Disease Control (CDC) reported that rates of autism had increased once again, now at an estimated 1 in 59 children up from 1 in 68 just two years ago. Rates have been climbing steadily since 2007 when the CDC initially estimated that 1 in 150 children were on the autism spectrum.
Some clinicians are concerned that the creeping expansion of autism is causing the diagnosis to lose its meaning.
The standard explanation for this increase has been the expansion of the definition of autism to include milder forms like Asperger's, as well as a heightened awareness of the condition that has improved screening efforts. For example, the most recent jump is attributed to children in minority communities being diagnosed who might have previously gone under the radar. In addition, more federally funded resources are available to children with autism than other types of developmental disorders, which may prompt families or physicians to push harder for a diagnosis.
Some clinicians are concerned that the creeping expansion of autism is causing the diagnosis to lose its meaning. William Graf, a pediatric neurologist at Connecticut Children's Medical Center, says that when a nurse tells him that a new patient has a history of autism, the term is no longer a useful description. "Even though I know this topic extremely well, I cannot picture the child anymore," he says. "Use the words mild, moderate, or severe. Just give me a couple more clues, because when you say autism today, I have no idea what people are talking about anymore."
Genetic testing has emerged as one potential way to remedy the overly broad label by narrowing down a heterogeneous diagnosis to a specific genetic disorder. According to Suma Shankar, a medical geneticist at the University of California, Davis, up to 60 percent of autism cases could be attributed to underlying genetic causes. Common examples include Fragile X Syndrome or Rett Syndrome—neurodevelopmental disorders that are caused by mutations in individual genes and are behaviorally classified as autism.
With more than 500 different mutations associated with autism, very few additional diagnoses provide meaningful information.
Having a genetic diagnosis in addition to an autism diagnosis can help families in several ways, says Shankar. Knowing the genetic origin can alert families to other potential health problems that are linked to the mutation, such as heart defects or problems with the immune system. It may also help clinicians provide more targeted behavioral therapies and could one day lead to the development of drug treatments for underlying neurochemical abnormalities. "It will pave the way to begin to tease out treatments," Shankar says.
When a doctor diagnoses a child as having a specific genetic condition, the label of autism is still kept because it is more well-known and gives the child access to more state-funded resources. Children can thus be diagnosed with multiple conditions: autism spectrum disorder and their specific gene mutation. However, with more than 500 different mutations associated with autism, very few additional diagnoses provide meaningful information. What's more, the presence or absence of a mutation doesn't necessarily indicate whether the child is on the mild or severe end of the autism spectrum.
Because of this, Graf doubts that genetic classifications are really that useful. He tells the story of a boy with epilepsy and severe intellectual disabilities who was diagnosed with autism as a young child. Years later, Graf ordered genetic testing for the boy and discovered that he had a mutation in the gene SYNGAP1. However, this knowledge didn't change the boy's autism status. "That diagnosis [SYNGAP1] turns out to be very specific for him, but it will never be a household name. Biologically it's good to know, and now it's all over his chart. But on a societal level he still needs this catch-all label [of autism]," Graf says.
"It gives some information, but to what degree does that change treatment or prognosis?"
Jennifer Singh, a sociologist at Georgia Tech who wrote the book Multiple Autisms: Spectrums of Advocacy and Genomic Science, agrees. "I don't know that the knowledge gained from just having a gene that's linked to autism," is that beneficial, she says. "It gives some information, but to what degree does that change treatment or prognosis? Because at the end of the day you have to address the issues that are at hand, whatever they might be."
As more children are diagnosed with autism, knowledge of the underlying genetic mutation causing the condition could help families better understand the diagnosis and anticipate their child's developmental trajectory. However, for the vast majority, an additional label provides little clarity or consolation.
Instead of spending money on genetic screens, Singh thinks the resources would be better used on additional services for people who don't have access to behavioral, speech, or occupational therapy. "Things that are really going to matter for this child in their future," she says.
The Top Five Mysteries of the Human Gut Microbiome
A scholar of science, circa 2218, might look back on this era and wonder why, all of a sudden, scientists became so obsessed with human stool. Or more accurately, the microorganisms therein.
Although every human is nearly identical genetically, each person carries around a massively different variety of microbial genes from bacteria, fungi, viruses, and archaea.
This scholar might find, for example, the seven-fold increase in PubMed articles on "gut microbiome" in the half-decade between 2012 and 2017; the plastic detritus of millions of fecal sample collection kits, and evidence that freezers in research labs worldwide had filled up with fecal samples. What's happened?
Human genome science has led to some important medical insights over time. Now it's moving over for the microorganisms. Because, although every human is nearly identical genetically, each person carries around a massively different variety of microbial genes from bacteria, fungi, viruses, and archaea—genes that are collectively called the microbiome.
Thinking that more knowledge about the gut microbiome is going to solve every problem in medicine is pure hubris. And yet these microorganisms seem to be at the nexus of humans and our environment, capable of changing us metabolically and adjusting our immune systems. What might they have the power to do?
Here are five of the most important questions that lie ahead for microbiome science.
1) What makes a gut microbiome 'healthy'?
The words "healthy microbiome" should raise a red flag. Because, currently, if scientists examine the gut microbial community of a single individual they have no way of knowing whether or not it qualifies as healthy—nor even what parameter to look at in order to find out. Is it only the names of the bugs that matter, or is it their diversity? Alternatively, is it function—what they're genetically equipped to do?
The words "healthy microbiome" should raise a red flag.
The focused efforts of the Human Microbiome Project were supposed to accomplish the apparently simple task of defining a healthy microbiome, but no clear answers emerged. If researchers could identify the parameters of a healthy microbiota per se, they might have a way to know whether manipulations—from probiotics to fecal transplant—were making a difference that could lead to a good health outcome.
2) Diet can manipulate gut microbes. How does this affect health?
"Many kinds of bacteria in our gut, they're changeable by changing our diet," says Liping Zhao of Shanghai Jiao Tong University in China, citing two large population studies from 2016. What's murkier is how this effects a change in health status.
Zhao's research focuses on making the three-way link between diet, gut microbiota, and health outcome. Meanwhile, researchers like Genelle Healey at the University of British Columbia (UBC) are working to track how the gut microbiome and health respond to a dietary intervention in a personalized way.
Knowing how the diet-induced changes in gut microbes affected health in the long term would allow every individual to toss out the diet books and figure out a dietary pattern—probably as personal as their gut microbes—that would result in their best health down the line.
If scientists could find how to harness one or more microorganisms to have specific effects on the immune system, they might be able to crack a new class of therapeutics.
3) How can gut microorganisms be used to fine-tune the immune system?
Many chronic diseases—autoimmune conditions but also, according to the latest research, obesity and cardiovascular disease—are immune mediated. Kenya Honda of Keio University School of Medicine in Tokyo, Yasmine Belkaid of the US National Institutes of Health (NIH), June Round at University of Utah, and many other researchers are chasing the ways in which gut microbes 'talk' to the immune system. But it's more than just studying certain bugs.
"It's an incredibly complex situation and we can't just label bugs as pro-inflammatory or anti-inflammatory. It's very context-dependent," says Justin Sonnenburg of Stanford. But if scientists could find how to harness a microorganism or group of them to have specific effects on the immune system, they might be able to crack a new class of therapeutics that could change the course of immune-mediated diseases.
4) How can a person's gut microbiome be reconfigured in a lasting way?
Measures of the adult microbiome over time show it has a high degree of stability—in fact, it can be downright stubborn. But a new, stable gut microbial ecology can be achieved when someone receives a fecal transplant for recurrent C. difficile infection. Work by Eric Alm of Massachusetts Institute of Technology (MIT) and others have shown the recipient's gut microbiota ends up looking more like the donor's, with engraftment of particular strains.
But what are the microorganisms' 'rules of engraftment'? Knowing this, it might be possible to intervene in a number of disease-associated microbiome states, changing them in a way that changed the course of the disease.
Is the infant microbiome, as shaped by birth mode and diet, responsible for health issues later in life?
5) How do early-life shapers of the gut microbiome affect health status later on?
Researchers have found two main factors that appear to shape the gut microbiome in early life, at least temporarily: mode of birth (whether vaginal or Cesarean section), and early life diet (whether formula or breast milk). These same factors are associated with an increased risk of immune and metabolic diseases. So is the infant microbiome, as shaped by birth mode and diet, responsible for health issues later in life?
Brett Finlay of the University of British Columbia has made these 'hygiene hypothesis' compatible links between the absence of certain bacteria in early life and asthma later on. "I think the bugs are shaping and pushing how our immune system develops, and if very early in life you don't have those things, it goes to a more allergic-type immune system. If you do have those bugs it gets pushed towards more normal," he says. The work could lead to targeted manipulation of the microbiome in early life to offset negative health effects.
By the time you reach for that head of lettuce at the grocery store, it's already probably traveled hundreds of miles and spent almost two weeks sitting in a truck.
"Food is no longer grown for human beings, it's grown for a truck to support a supply chain," says the president of Metropolis Farms in Philadelphia.
But everyone likes fresh produce, so the closer your veggies are grown to your favorite supermarket or restaurant, the better. With the recent outbreak of E.coli contaminating romaine lettuce across the United States, it's especially appealing to know that your produce has been grown nearby in a safe environment. How about a farm right on top of a grocery store in Philadelphia? Or one underground in the heart of Manhattan? Or one inside an iconic restaurant in Australia?
Hyper-local urban farming is providing some consumers with instant access to seriously fresh produce. It's also a way for restaurants and food suppliers to save on costs, eliminating the need for expensive packaging and shipping, experts say. Tour five of the world's coolest vertical farms in pictures below.
NEW YORK
Farm.One's vision is to build small indoor farms in cities around the country that provide rare herbs and produce to high-end restaurants. Their farm in the heart of Manhattan occupies 1200 square feet in a basement beneath the two-Michelin-starred restaurant Atera, which is conveniently one of their customers. All of the 20 to 25 restaurants they supply to are within a three-mile radius, making delivery possible by subway or bike.
"We have a direct connection with the chefs," says the CEO and founder Robert Laing. "For very perishable produce like herbs and leafy greens, hyper-local vertical farming works really well. It's literally dying the moment you cut it, and this is designed to be fresh."
PHILADELPHIA
"Restaurants are important," says Jack Griffin, the president of the indoor vertical Metropolis Farms in Philadelphia. "But not the most important, because they don't feed the majority of people."
Griffin is on a mission to standardize the indoor farming industry so supermarkets and communities around the world can benefit from the technology in a cost-effective and accessible way. Right now, Metropolis Farms supplies to a local grocer, Di Brunos Bros, that is less than two miles from their facility. In the future, they have plans to build a rooftop greenhouse atop a new supermarket in Philadelphia, plus indoor farms in Baltimore, Oklahoma, and as far away as India.
One advantage of their farms, says Griffin, is their proprietary technology. An adaptive lighting system allows them to grow almost any size crop, including tomatoes, cucumbers, peppers, strawberries, and even giant sunflowers.
"It's bigger than just food," he explains. "We are working on growing specialty crops like wine, chocolate, and coffee. All these plants are within reach, and we can cut the cord between supply chains that are difficult to deal with. Can you imagine if you grew Napa wines in Camden, New Jersey?"
BERLIN
GOOD BANK, in Berlin, bills itself as the world's first farm-to-table vertical restaurant. They grow their many of their own vegetables and salads onsite using farming system technology from another German company called INFARM. The latter's co-founder and CEO, Erez Galonska, cites a decline in traditional farming, an increase in urban populations, and the inefficiency of the current food system as motivation for turning to vertical farming to produce food where people actually eat and live.
"INFARM is pioneering on-demand farming services to help cities become self-sufficient in their food production, while eliminating waste and reducing their environmental impact," Galonska says.
MELBOURNE
Melbourne-based Farmwall leases indoor vertical farms the size of small bookshelves to restaurants and cafes. The farms are designed to be visually appealing, with fish tanks at the bottom supplying nutrient-rich water to the hemp media in which herbs and microgreens grow under LED lights. As part of the subscription model, urban farmers come once a week to check water levels, bring new trays of greens, and maintain the system. So far, two restaurants have signed up -- Top Paddock, in the suburb of Richmond, and Higher Ground, an internationally recognized restaurant in Melbourne.
"It's worth it to the restaurants because they get fresh produce at their fingertips and it has all the benefits of having a garden out back without any of the work," says Serena Lee, Farmwall's co-founder and chief communications officer.
The sky's the limit for future venue possibilities: nursing homes, schools, hotel lobbies, businesses, homes.
"Urban farming is never going to feed the world," Lee acknowledges. "We understand that and we're not saying it will, but when people are able to watch their food grow onsite, it triggers an awareness of local food production. It teaches people about how technology and science can work in coherence with nature to create something super-efficient, sustainable, and beautiful."
LOS ANGELES
At the restaurant Otium in Los Angeles, a peaceful rooftop garden sits atop a structure of concrete and steel that overlooks the hustle and bustle of downtown LA. Vegetables and herbs grown on the roof include Red Ribbon Sorrel, fennel fronds, borage blossoms, nasturtium, bush basil, mustard frills, mustard greens, kale, arugula, petit leaf lettuce, and mizuna. Chef Timothy Hollingsworth delights in Otium's ability to grow herbs that local purveyors don't offer, like the wild Middle Eastern Za'atar he uses on grilled steak with onions and sumac.
"I don't think this growing trend [of urban farming] is something that will be limited to a handful of restaurants," says Hollingsworth. "Every business should be concerned with sustainability and strive to protect the environment, so I think we will be seeing more and more gardening efforts throughout the country."
Whether a garden is vertical or horizontal, indoors or outdoors, on a roof or in a basement, tending to one provides not only fresh food, but intangible benefits as well.
"When you put your time and love into something," says Hollingsworth, "it really makes you respect and appreciate the produce from every stage of its life."
Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.