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The most important stories for you to know today
  • New maps require some homes to be fire resistant

    Topline:

    California is one of the few states with building codes that require using fire-resistant materials in places prone to wildfires. The release of new maps outlining fire hazard zones throughout the state mean that for some homeowners in the urban center of Altadena, the rebuilding requirements are about to change in the coming months.


    Expanded wildfire zones: California fire officials just released long-awaited maps that expand the areas where wildfire building codes apply and that show fire risk is only increasing. In the footprint of the Eaton Fire that hit Altadena, the expanded zone for wildfire building codes now includes more than 500 additional homes and buildings, according to an analysis by NPR.

    More changes to come: Beginning in 2026, building requirements will expand again to include any properties in the "high" hazard category of the wildfire maps. That will mean about 1,000 additional properties in the Eaton Fire area will be required to use wildfire building codes, if their permits are approved next year.

    Read on . . . to learn more about the construction of fire-resistant homes.

    Homeowners in Los Angeles have started the long process of rebuilding after the destructive wildfires in January. Some are constructing homes that are much less likely to burn when the next wildfire hits. That's because California is one of the few states with building codes that require using fire-resistant materials in places prone to wildfires.

    Still, thousands of other homeowners in the urban center of Altadena are about to rebuild without wildfire-resistant materials, because they live outside a state-designated wildfire zone.

    For some of those people, the rebuilding requirements are about to change in the coming months.

    California fire officials just released long-awaited maps that expand the areas where wildfire building codes apply and that show fire risk is only increasing. Under the new maps, an additional 1.4 million acres statewide is now considered at high or very high risk on land for which local governments are responsible.

    In the footprint of the Eaton Fire that hit Altadena, the expanded zone for wildfire building codes now includes more than 500 additional homes and buildings, according to an analysis by NPR. Los Angeles County must adopt the new zones by late July, which means those property owners have roughly four months before the more stringent rules take effect.

    The move is a rare example of a community strengthening rebuilding rules after a disaster, in the hope of preventing similar destruction in the future. Governments often loosen construction and permitting rules after disasters, facing immense pressure to speed up the rebuilding process.

    Remains of a burned out home that include pieces of wood, a burned out washer and dryer and other indistinguishable items
    Patrick and Ruth Fong's home burned home still shows signs of the toys their kids used to play with. After late July, rebuilding it will require meeting wildfire building codes, based on new state regulations.
    (
    Lauren Sommer/NPR
    )

    Research shows fire-resistant construction can dramatically improve the chances that a house survives. Many of the building materials are commonly available, like fiber cement siding, and overall, construction costs can be roughly the same as a standard house.

    Still, even with the newly expanded zones, more than 7,800 buildings in the area burned by the Eaton Fire fall outside those zones and won't have to follow the more protective wildfire building codes. Wildfire experts say with so many houses to rebuild, Los Angeles is facing a critical moment to ensure communities are better prepared for future disasters. Wildfires are getting more intense and are spreading faster as the climate gets hotter, and across the Western U.S., many homes rebuilt after fires aren't constructed to withstand future ones.

    "If homes are being rebuilt, they should be built with wildfire in mind because unfortunately we do know that risks are increasing," says Kimiko Barrett, senior wildfire researcher at Headwaters Economics, a non-profit think tank. "History repeats itself. This will not be the only time that L.A. experiences a catastrophic wildfire."

    Weighing how to rebuild

    When Patrick and Ruth Fong look over the charred debris that used to be their Altadena home, they still see where their three kids used to play. The burned frames of the kids' bikes are visible under the crumbled garage door. A blackened, metal ring in the backyard shows where the trampoline once was.

    "This is the only house our kids remember," Ruth says. "We were only able to recover some mugs and the kids' clay objects they made in art class at school."

    Now, two months after the disaster, they're also starting to envision what could be. They've met with a contractor to plan what they'll rebuild and are now finalizing the floorplan.

    "There's been so much grief and sadness, but then you have some glimmers of hope," Ruth says.

    A man wearing a black jacket and a woman wearing a brown jacket stand side by side in front of the remains of their burned out home.
    Ruth and Patrick Fong debated whether to stay in Altadena after they lost their house in the Eaton Fire. It's the second time a wildfire has burned the property.
    (
    Lauren Sommer/NPR
    )

    Just after the fire, the Fongs weren't sure they wanted to stay. Altadena sits next to the dry shrubland of the San Gabriel Mountains and this was the second wildfire to hit their property. Before the Fongs owned it, the Kinneloa Fire also destroyed the home in 1993.

    "We had in our heads, we have to build it and sell it, because what if it happens again?" Patrick says. "You know, all these terrible things we're thinking about."

    But like many Altadena residents, the Fongs feel connected to their community and especially close to neighbors on their cul de sac. So, they've started talking to their contractor about ways to make the house better able to withstand a wildfire by using fire-resistant building materials. That cost has to be balanced with the other financial constraints of rebuilding, as the Fongs figure out how far their insurance settlement will go.

    "With fireproof construction, how much more is that going to be and how much can we really afford?" Patrick says. "Because we're already maxing out our policy."

    Newly expanded fire zones show homes at risk

    Like thousands of other Altadena residents, the Fongs so far are not required to rebuild with fire resistant materials. That's because California's wildfire building codes, known as "chapter 7A," only apply in areas that are deemed to be at risk. Those "wildfire hazard zones," as they're known, are mapped by California's Department of Forestry and Fire Protection.

    California's wildfire hazard maps are the bedrock of the state's wildfire policies. In addition to determining where wildfire building codes apply for new construction, property owners in very high risk zones must clear flammable vegetation around buildings. Wildfire hazard zones must also be taken into consideration in land use planning by local governments, including ensuring there are enough evacuation routes.


    The maps were first released in 2008, putting California on the forefront of wildfire planning. Many Western states still lack statewide fire risk maps. But as wildfires have become more extreme, fire experts pushed California to update the maps, since the original maps only forecast fires under fairly weak wind speeds and don't take into account high wind conditions that can drive bigger infernos. (Insurance companies typically have their own wildfire risk maps that they use to determine rates for customers.)

    The newly released wildfire zones include properties that burned in the Eaton Fire. Pacific Palisades, where the other major fire burned in January, was already in a high risk wildfire zone, so wildfire building codes apply to the more than 6,800 buildings destroyed there.

    Under state law, Los Angeles County must adopt the new wildfire hazard maps by July 22nd. According to the Los Angeles County Fire Department, that means if residents in the newly expanded zones get their building permits approved after the maps are adopted, the wildfire building codes will apply.

    Beginning in 2026, the requirements will expand again to include any properties in the "high" hazard category of the wildfire maps. That will mean about 1,000 additional properties in the Eaton Fire area will be required to use wildfire building codes, if their permits are approved next year.

    Still, even with the new wildfire maps, the majority of homes destroyed in the Eaton Fire won't be required to be built to resist future wildfires. California's maps calculate the hazard from fires spreading in wildland areas, but don't take into account what happens when fires spread from house to house.

    "I thought the very high fire severity zones were really going to reach deep, deep down into Altadena, and they haven't," says Los Angeles County Fire Department deputy fire chief Albert Yanagisawa.

    The costs and benefits of wildfire building codes

    The change in the maps is causing some nervousness in Altadena.

    "Some people I see rushing to decide what their rebuild is before that map comes out, which puts into question whether they're thinking about the community or their bottom line," says Nic Arnzen, a member of the Altadena Town Council.

    Researchers have shown that using fire-resistant materials makes homes less likely to burn, especially since most homes are ignited by tiny embers carried by the wind. Even in an extreme wildfire, fire inspectors find some houses remain seemingly untouched, like in the Los Angeles fires as well as the wildfire in Lahaina, Maui.

    One study found houses built with California's wildfire building codes are 40% more likely to survive. An analysis by FEMA found using California's building codes could save $24 billion in damages to single-family residences over a 75-year timeframe.

    California's wildfire building code calls for fire-resistant roofs and siding, as well as using attic vents that don't allow embers to be blown inside a house. It also calls for enclosing roof eaves so the undersides are less prone to igniting. They only apply for new construction or when houses have a major renovation.

    A chimney and a wall remains standing after a home burned to the ground. The former home sits on a dry hillside without any greenery and a mountain is pictured in the distance
    Altadena is likely to face more wildfires, experts say, so rebuilding after the Eaton Fire is a crucial time to make the community more resilient to fires.
    (
    Lauren Sommer/NPR
    )

    "These are often materials commonly used on the market, widely available," Barrett says. "Things like asphalt roofs. Things like Hardie plank fiber cement siding. Very, very common, very affordable."

    The additional cost of meeting the codes can be a few thousands dollars, according to a study from Headwater Economics and the Insurance Institute for Business & Home Safety, a research group funded by the insurance industry. Adding even more fire-resistant features, or more costly options like metal roofing, can add up to 13% to the overall construction cost.

    Some Los Angeles homeowners could find the additional costs will be paid by their insurance company, if the policy specifies it covers bringing a house up to code. Still, not all policies cover those costs.

    Los Angeles County officials say they're looking for funding options for homeowners who might struggle with the costs.

    "One of the commitments I've made is looking at grant opportunities to see where we can allow people to apply that may not be able to afford it, to harden or do things that would benefit in case of future fires, and see how we can offset the cost," says Los Angeles County supervisor Kathryn Barger.

    Rebuilding Los Angeles with wildfires in mind

    With a history of frequent wildfires, Los Angeles has long understood how vulnerable many neighborhoods are. Some homeowners rebuilding after the Eaton Fire aren't likely to follow wildfire building codes if they're not required to, especially given that some are underinsured.

    "Even if they're not going to have to comply, we're going to be strongly encouraging it for future resiliency," says Amy Bodek, director of regional planning for the County of Los Angeles. "We've been on this trajectory to look at long range plans that will prevent future disasters from affecting so many people. We're certainly not going to prevent the disasters, but how can we minimize strategically the harm to individuals and properties?"

    Los Angeles County recently limited the amount of housing that can be built in the foothills of Altadena, where wildfire risk is highest. The region is facing a massive housing shortage, but considering the fire risk, is directing development to denser urban corridors closer to public transit.

    Altadena officials say they're hoping to rebuild a much safer community, including putting electric power lines underground so they pose less of a risk. Utility lines have started wildfires in high winds and are still being investigated as a cause of the Eaton Fire.

    "We have an opportunity to show people how to create a community that can live in peace and harmony with the natural disasters around them," Arnzen says. "I don't want to waste the opportunity."

    Brent Jones contributed to this story.
    Copyright 2025 NPR

  • Unhoused man died after entering interim housing
    Exterior of the Mayfair hotel in Koreatown
    Raz Chowdhury, a 45-year-old unhoused man, died at The Mayfair in July 2026 after being moved to hotel as part of the Inside Safe program.

    Topline:

    45-year-old Raz Chowdhury was moved off the streets into interim housing through an Inside Safe operation. A week later, he was found dead in his hotel room.


    The backstory: L.A. Mayor Karen Bass’ office said it does not disclose the locations where an individual is placed following an Inside Safe operation. According to Ktown for All, Chowdhury died at the Mayfair Hotel in Westlake, which is used for interim housing.

    A spokesperson for the Los Angeles County Department of Medical Examiner said the case is still under investigation and Chowdhury died at a hotel in the 1200 block of West 7th Street.

    This story first appeared on The LA Local.

    A week after 45-year-old Raz Chowdhury was moved off the streets into interim housing through an Inside Safe operation, he was found dead in his hotel room.

    Chowdhury had spent years living on the streets of Koreatown, moving between encampments along Sixth Street and Wilshire Boulevard and Manhattan Place.

    Sherin Varghese first met him three or four years ago. Chowdhury would reach out to Varghese, a volunteer with Ktown for All, an advocacy group that provides direct aid for people experiencing homelessness in Koreatown. He would ask her for tents, tarps, clothes and other supplies. More often than not, she said, they weren’t for him.

    “He would always go above and beyond to take care of the people around him,” Varghese said at a vigil for Chowdhury on Saturday, Aug. 29.

    Once, after Chowdhury lost his phone during a sanitation sweep, he searched for Varghese online and found her work number. He called to ask if she could bring tents and tarps for him and other people whose belongings were lost in the sweep.

    “He was resourceful, he was reliable, and he was so thoughtful about the way that he talked about how all of this affected him and affected his friends,” Varghese said.

    On June 25, Chowdhury was among 31 people moved into housing during an Inside Safe operation at Wilshire Boulevard and Manhattan Place, according to Mayor Karen Bass’ office.

    A week later he was dead.

    What happened after Inside Safe

    According to Ktown for All, Chowdhury died at the Mayfair Hotel in Westlake, which is used for interim housing.

    A spokesperson for the Los Angeles County Department of Medical Examiner said the case is still under investigation and Chowdhury died at a hotel in the 1200 block of West 7th Street on July 2. His cause of death is listed as deferred and the case is under investigation by the Los Angeles Police Department’s Rampart Division.

    The Los Angeles Homeless Services Authority, which oversees the Mayfair, would not say if Chowdhury was a resident when he died. An agency spokesperson said they cannot confirm an individual’s enrollment in a LAHSA-contracted program without a written release from next of kin.

    LAHSA’s latest Inside Safe report shows that 6,406 people had entered interim housing through the program as of July 31. About 1,750 people remained in interim housing, including 289 at the Mayfair. Meanwhile, 1,802 people, or more than one in four who entered the program, had returned to homelessness. Another 126 people, or about 2%, were listed as deceased.

    Bass’ office said it does not disclose the locations where an individual is placed following an Inside Safe operation.

    Once someone is connected to interim housing, ongoing services and case management are handled by a LAHSA-contracted service provider, mayor spokesperson Jieun Kim said.

    Remembering Chowdhury

    The people who knew Chowdhury gathered last week to remember him at the site of the encampment where he had lived at Wilshire Boulevard and Manhattan Place.

    A little more than two dozen people attended the memorial, where they placed flowers at the base of a small tribute to him.

    Planters now line the sidewalk where the tents once were. Several people cried as they shared memories of Chowdhury, who they said spent years looking out for others living on the streets of Koreatown.

    Cynthia Zhang, who has volunteered with Ktown for All for about four to five years, remembers visiting an encampment where Chowdhury was staying after the Los Angeles fires. Newly displaced people there told her they felt safer with that community than they did at shelters.

    “I think Raz was really instrumental in helping create that kind of space,” Zhang said at the vigil.

    The last time Zhang saw Chowdhury, he had moved again and did not have a lot of his stuff. But he had a new puppy named T-Rex and seemed to be in good spirits.

    “He had a really lovely smile,” Zhang said. “I just remember him skateboarding around … all these little things, maybe because I didn’t see him every day, it really does feel like I’ll be walking around and I’ll see him in one of our old spots.”

    David Strugar, another longtime Ktown for All volunteer, said Chowdhury was often the person volunteers went to when they wanted to know how people in the area were doing.

    “I would always point him out and say, ‘That’s the mayor of this area,’ because wherever he was, he was just the center of it, and he took care of people,” Strugar said.

    Chowdhury would tell volunteers who needed what and help distribute supplies, Strugar said.

    A few weeks before he died, Varghese said, she and Chowdhury were looking for places where he could stay outside a 41.18 zone, where the city restricts sitting, lying, sleeping and storing personal property in certain public rights-of-way under specified circumstances.

    Then Inside Safe moved him indoors.

    “I hoped that he’d be one of its success stories, but a week later, he was gone,” Varghese said. “The program is called Inside Safe, but for Raz and 125 others, it wasn’t that. And it was never going to be Inside Safe, and it was never going to be easy to be inside alone for someone who had so much to give and always surrounded himself with people to take care of.”

    The last time Strugar saw Chowdhury, he had his dog T-Rex with him. Ktown for All volunteers don’t know where T-Rex is now.

    Chowdhury believed he had the right to community and companionship, Strugar said.

    “And there are so many people who have so much and won’t give anything,” Strugar said. “And Raz kept having everything taken away from him, and he still ended up being the person to give.”

    He added, “I just keep expecting to walk around the corner and see him, and I’m angry that I won’t.”

  • Sponsored message
  • SoCal is a launchpad
    A sign of the company Miniso's red shopping bag logo.
    A MINISO logo is displayed on a sign outside of a store in San Diego.

    Topline:

    SoCal has become a proving ground for some of the country’s fastest-growing Asian and Asian American retailers, giving chains like Miniso and 99 Ranch Market an early test of broader U.S. appeal.

    Growing fast: On the National Retail Federation’s 2026 Hot 25 list, Miniso ranks No. 1, Daiso No. 3, Uniqlo parent Fast Retailing No. 6 and 99 Ranch Market No. 15.

    Backstory: All four have had a Southern California presence for years, giving them experience in one of the country’s most diverse and competitive retail markets.

    Southern Californians who’ve long shopped at Daiso, Miniso, Uniqlo or 99 Ranch Market may not be surprised to see the Asian-rooted chains expand across the country.

    But that growth is now showing up in the numbers.

    The National Retail Federation’s Hot 25 Retailers list ranks retailers by U.S. sales growth from 2024 to 2025. Miniso tops the list, with sales up nearly 53%.

    The Chinese chain of gift shops opened its first U.S. store in Pasadena’s Old Town more than nine years ago and is now aiming to grow its American footprint to nearly 500 stores this year.

    “If you can make it in Southern California, that's great,” said David Marcotte, senior vice president of global retail and technology at Kantar and an author of the NRF list.

    A store clerk gathers grocery carts outside a 99 Ranch supermarket
    A 99 Ranch market opened in 2023 in Eastvale.
    (
    Gina Ferazzi
    /
    Los Angeles Times via Getty Images
    )

    Marcotte says succeeding in California’s highly competitive retail market can teach chains lessons that translate elsewhere.

    “The stone-cold reason is quality. The second one is experience,” he said. “Those are the two things that when shoppers go into any retailer, they’re looking for.”

    Daiso ranks third, with growth of nearly 26%, while another Japanese company, Fast Retailing — the parent company of Uniqlo — comes in sixth.

    99 Ranch Market, an American supermarket chain founded in Orange County that specializes in Asian groceries, comes in 15th.

    Marcotte says Southern California has been a logical landing spot for these companies because of its proximity to Asia. But Marcotte says it can also be an unforgiving place to launch because of the competition, and he often encourages the clients he advises to consider smaller markets.

    “I said if you open in Southern California, open one store, get it right,” Marcotte said. “If you get it wrong, you're dead. You'll never recover. You'll have to leave the country and come back in.”

    The supermarket industry is particularly tough to break into because customers here, he says, have plenty of alternatives if the quality, selection or experience falls short.

    He also emphasizes a retailer in California focused on Asian goods will see more success serving Chinese, Filipino and other Asian customers rather than designing around a particular ethnic group.

    “That type of diversity of Asian customers that you have to address in the same store is what really proves to be the difference for an Asian retailer in the California market,” Marcotte said.

    That’s part of the business model for 99 Ranch, which was founded by a Taiwanese immigrant who opened the first location in Westminster's Little Saigon in 1984.

  • SoPas doctor makes backyard roast for fun
    An Asian man wearing glasses and an apron holds a roasted duck above a big outdoor oven.
    Hong Pham, aka That Peking Duck Guy, takes a roasted Pipa duck out of his outdoor oven.

    Topline:

    Radiologist Hong Pham has an unusual side hustle — cooking and selling Peking and roast ducks from his South Pasadena backyard.

    The backstory: That Peking Duck Guy started out as a social media account documenting Pham's culinary journey to make the perfect duck. It then became a side hustle when strangers and neighbors offered to buy his birds.

    Read on ... to learn about how Pham got started and how he cooks his ducks.

    Got a taste for ducks cooked the Chinese way? Your quest may take you to a quiet suburban backyard in South Pasadena.

    That's where That Peking Duck Guy cooks and sells his birds. His clients, he said, include Phil Rosenthal and Roy Choi.

    The guy behind That Peking Duck Guy is Hong Pham, who started the social media account in late 2025 as a way to document his latest culinary obsession: making the perfect duck, be it Peking or Pipa (deboned and flattened into the shape of the namesake Chinese string instrument).

    The intention was not to sell. "I have a day job," Pham said. A radiologist, to be precise.

    "I was actually making so many that neighbors wanted to claim it and offered to buy it," he added. "So I'm like, 'OK, that makes it easier 'cause I don't have to eat it all.'"

    Soon came DMs from strangers asking for the same thing.

    These days, That Peking Duck Guy caters events and holds takeout pop-ups where people can purchase and pick up a duck (which comes with sides and duck soup) from his South Pasadena backyard — right where he cooks them.

    A plate of duck served with Chinese sweet sauce, chopped spring onions and cucumber slices.
    Peking duck from That Peking Duck Guy served with Chinese sweet sauce, chopped spring onions and cucumber slices.
    (
    Fiona Ng
    /
    LAist
    )

    Duck is the latest obsession

    Duck is not his first rodeo. Pham said he and his wife are foodies who've always been curious about delving into Vietnamese and other Asian culinary traditions. For Pham, that also means replicating some of these dishes at home, from scratch.

    He'd gone on a tofu bender — making gallons of the stuff, as blocks, drinks and pudding — and also a bánh cuốn spree, or Vietnamese steamed rice rolls. He landed on duck as his latest subject only because he had wanted to make better heo quay, or Vietnamese roasted pork belly.

    It's the oven

    An Asian man in glasses and an apron smiling next to a spaceship-like outdoor oven.
    Pham and one of his special outdoor ovens he uses to roast duck.
    (
    Fiona Ng
    /
    LAist
    )

    He researched how to get that extra crisp online and landed on an oven people in Asia use to make roast and Peking ducks.

    How to get your duck

    Pham hosts takeout pop-ups from South Pasadena backyard. Follow That Peking Duck Guy's Instagram for updates.

    Visit the official website for catering requests.

    "It was called the Apollo oven 'cause it looks like an Apollo space capsule," he said.

    He bought one and then another. In between, he experimented cooking different meats with the new oven to get a feel before turning to the waterfowl.

    He even got advice from Top Chef winner Mei Lin, whom he messaged cold: "She's like, 'Keep it simple. Keep it basic. Keep it traditional.'"

    Three ducks inside an outdoor oven
    Three Pipa ducks inside the oven.
    (
    Fiona Ng
    /
    LAist
    )

    Hundreds of ducks later, Pham said he still learns something new. That's one reason why his side hustle has stuck around.

    "I didn't create like, you know, That Bánh Cuốn Man," he said. "Yeah, duck's gonna last."

    How That Peking Duck Guy cooks his ducks

    Pham starts 7 to 10 days before cooking. Here's the preparation process:

    1. He usually trims off the legs and the wings, because those parts get burnt in the oven.
    2. He insufflates the duck. He sticks an air pump in between the meat and the skin to separate the two, so the entire duck blows up into a "huge balloon essentially," he said.
    3. He scalds the skin with a combination of vinegar and maltose to make it "aerodynamic and tight" to get that crispiness.
    4. He seasons the inside of the duck.
    5. He then hangs and dries the ducks for about 7 to 10 days.
    6. Then in the Apollo oven they go. Peking ducks take about an hour and 15 minutes to cook. Pipa ducks take about 40 minutes.

    When does he know they're done? "Well, you know the color, we're looking for that beautiful mahogany glistening skin, you know?" Pham said.

    Two freshly cooked roast ducks.
    Two Pipa ducks fresh out of the oven.
    (
    Fiona Ng
    /
    LAist
    )

  • UC scientists map interactions in new research

    Topline:

    Scientists have now gotten closer to understanding how gene mutations may lead some people to develop profound autism.

    Why it matters: A team of researchers from UC San Francisco mapped more than a thousand interactions between many proteins that come from certain autism risk genes.

    Why now: This molecular atlas, published in the journal Science, could point researchers toward new and promising treatments.

    Scientists have now gotten closer to understanding how gene mutations may lead some people to develop profound autism.

    The clues, they say, lie in the murky space between genes and disease — where key proteins come together and interact.

    A team of researchers from UC San Francisco mapped more than a thousand interactions between many proteins that come from certain autism risk genes. This molecular atlas, published in the journal Science, could point researchers toward new and promising treatments.

    "It's an unprecedented resource for the field," says Dr. Daniel Geschwind, a professor of human genetics, neurology, and psychiatry at UCLA who was not involved with the study. "A lot of people interested in understanding autism and drug development are going to be using this."

    For families affected by profound autism, it offers hope for eventual drug therapies. "This is the kind of scientific advance we have been waiting for and praying for," says Alison Singer, president of the nonprofit Autism Science Foundation, who has a daughter with severe cognitive impairment. "There's still a lot of work ahead, [but] this paper makes the path from genetic discovery to treatment much clearer."

    The work builds on progress made in recent years to identify single genes that harbor mutations found in a subset of individuals with profound autism.

    Getting past the "wall"

    People with profound autism often live with severe intellectual disability and require around-the-clock care. They're nonverbal or minimally verbal, and often have serious medical conditions like epilepsy.

    Pinning down the biology behind profound autism has always been a complicated endeavor — while both genes and environmental factors play a role, those factors can vary widely from person to person.

    In the past decade or so, some genetics researchers have had remarkable success in identifying high-impact genetic differences in a subset of people with profound autism.

    "They've discovered several hundred genes and corresponding mutations that are prevalent in [these] individuals," says Nevan Krogan, director of the Quantitative Biosciences Institute at UC San Francisco.

    "But they kind of hit a wall," he added — because scientists haven't been able to turn those gene discoveries into many promising drugs and treatments.

    "There was this huge missing piece," says Dr. Matthew State, a clinical psychiatrist and geneticist at UCSF: The genes serve as blueprints for making proteins that drive brain development, but researchers lacked visibility into how those proteins do the work.

    State has been a pioneer in identifying high-risk genes, and the mutations in those genes, that are associated with profound autism. Krogan has been at the forefront of using new technology to look into protein interactions.

    More than a decade ago, the two researchers were introduced by their mutual boss, the chancellor at UCSF, who encouraged them to collaborate. "[State] had the genes and the mutations. I had the technologies to look at the corresponding proteins," Krogan says.

    They focused on filling a knowledge gap. "What we've been missing is the mechanistic understanding of how these mutations [on the genes] are seemingly resulting in autism," Krogan says. "In order to understand that, you need to go to the proteins."

    Proteins are the complex molecules that come together to build the body, based on instructions encoded in the genes. "What makes an eye cell an eye cell, and a muscle a muscle, are the proteins and how they work together," State says. "They are the machinery of life."

    In this case, the researchers wanted to find the molecular machinery of profound autism — to understand which proteins came from those high-risk autism genes, and how those proteins worked together.

    The research was slow at first, but more recent advances in technology — including artificial intelligence — have sped things up.

    To start, the researchers went on a "fishing expedition" for protein interactions. They chose 100 proteins from these high-risk autism genes, injected them into lab-grown cells, and then pulled them out, along with the additional proteins that attached to them.

    Then, they used an AI system called AlphaFold, developed by Google DeepMind, to help determine which proteins in the clumps were directly touching. "Where AI is playing an important role is being predictive about who's talking to who," says Krogan. "Sometimes they take years to figure out. Now, we can get these insights in an hour." While imperfect, the system has worked well enough to save significant time and money, Krogan says.

    Then, they wanted to see what happened to the proteins when the genes got tweaked. They introduced mutations that appear in patients with profound autism, and assessed what changed. "We broke the proteins in the way that they're broken in autism," says State. "That allows us ultimately to answer the question of, when they're going wrong in autism, how are they going wrong?"

    They conducted this research in frogs and in organoids, which are lab-grown tissues that model the human brain. In one example, the mutations weakened the connection between two proteins related to which genes turn on and off in a cell. Then, one went rogue, turning on other genes that led to neurodevelopmental defects in organoids.

    Molecular convergence

    There are hundreds of rare, high-risk autism genes, acting in more than a thousand different ways.

    But in mapping more than 1,800 protein interactions, the researchers found that many of them moved along shared biological pathways — particularly those related to early brain development, such as how synapses get constructed, and which neurons develop and when.

    The convergence found in this study aligns with other recent publications, adding to an emerging understanding in the field, says Dr. Geschwind of UCLA.

    "If we look at multiple mutations and they converge on the same process, that's strong evidence that you're dealing with the things that you want to treat," State says.

    Identifying this more limited set of protein complexes that likely contribute to the development of profound autism could change the approach to treatments, says Singer with the Autism Science Foundation. "We've been working gene-by-gene to correct mutations," she says.

    And if future drugs could target these shared protein pathways, she adds, "we may not need that separate therapeutic strategy for every autism gene."

    Setting sights on new drug-development targets

    It takes years to go from a biological discovery like this to an approved drug that treats humans. The findings would need to be translated into drug candidates, then tested for safety and effectiveness.

    "It takes time and a lot of persistence and focus," State says. "This [paper] is unlikely to lead to therapies tomorrow — but it lays an important foundation for them."

    Most human drugs are made to target proteins, Geschwind at UCLA says, so the newly published map of protein interactions offers an accessible entry point for pharmaceutical development.

    And researchers hope to combine recent technological advances in ways that accelerate that progress even more. "When you put together the ability to borrow from successes in other fields [such as cancer treatments], and the development of AI, we're at an inflection point that will hopefully shorten the time cycle," State says.

    Last week, Krogan's Quantitative Biosciences Institute received a $46 million grant from the Aligning Research to Impact Autism initiative, funded by philanthropist and Google co-founder Sergey Brin. The researchers are already working on next steps.

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