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USC neuroscientist faces scrutiny following allegations of data manipulation

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USC neuroscientist faces scrutiny following allegations of data manipulation

A star neuroscientist at USC is facing allegations of misconduct after whistleblowers submitted a report to the National Institutes of Health that accused the professor of manipulating data in dozens of research papers and sounded alarms about an experimental stroke medication his company is developing.

The accusations against Berislav V. Zlokovic, professor and chair of the department of physiology and neuroscience at the Keck School of Medicine of USC, were made by a small group of independent researchers and reported in the journal Science.

The report identifies allegedly doctored images and data in 35 research papers in which Zlokovic is the sole common author. It also raised questions about findings in Phase II clinical trials of a drug called 3K3A-APC, an experimental stroke treatment sponsored by ZZ Biotech, the Houston-based company Zlokovic co-founded.

Preclinical data appeared to have been manipulated, the report authors allege. In addition, the Phase II results appear to contain errors that would skew interpretation of the data in favor of the drug.

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An attorney for Zlokovic said the neuroscientist takes the accusations “extremely seriously” and was “committed to fully cooperating” with a USC inquiry into the matter. However, he said his client could not comment on the allegations while the review was pending.

“Professor Zlokovic would normally welcome addressing every question raised, insofar as allegations are based on information and premises Professor Zlokovic knows to be completely incorrect,” attorney Alfredo X. Jarrin wrote in an email. “And other questions address work not performed at his lab or papers where he was not the senior author or contact author and his role was limited.”

The university also issued a statement saying it takes allegations of research integrity seriously. “Consistent with federal regulations and USC policies, the university forwards any such allegations to its Office of Research Integrity for careful review,” the university said in a statement. “Under USC policy, this review is required to be confidential. As a result, we are unable to provide any further information.”

Last year, USC’s Keck School of Medicine received from NIH the first $4 million of a planned $30-million grant to conduct Phase III trials of the experimental stroke treatment on 1,400 people.

Given the serious issues outlined in their report, the whistleblowers say those trials should be stopped immediately.

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“It should certainly be paused in my opinion,” said Matthew Schrag, an assistant professor of neurology at Vanderbilt and co-author of the whistleblower report. “There are red flags about the safety of that treatment.”

He said that evidence from the USC-led phase II trial of the drug, which was published in 2018 and called RHAPSODY, raised questions of patient safety. Patients in that trial were more likely to die in the week after treatment, and more likely to be disabled 90 days later than those who were given a placebo.

In addition, Schrag said, some patients given the placebo had to wait longer for the standard stroke treatment of the drug tPA or surgery to dissolve the blood clot.

“The faster you’re able to intervene to either restore blood flow with the drug or restore blood flow by removing the clot, the more brain cells survive,” he said.

He added that he did not believe the delay was intentional but that it had the effect of “skewing the results in favor of the drug.”

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Schrag previously raised questions about the integrity of other neurological research, work he said was separate from his employment at Vanderbilt.

Scientists have questioned Zlokovic’s research anonymously for years, Schrag said. Many of these concerns were published on PubPeer, a website on which anonymous contributors can examine scientific papers and highlight potential flaws.

Yet scientists working with Zlokovic did not complain publicly, he said, allowing the studies to continue for years and succeed at attracting tens of millions of dollars in taxpayer funding.

“I think people are concerned about the potential for backlash for harm to their own careers,” Schrag said. “And so I think that motivates people to just go along.”

In its report, the journal Science interviewed four former employees of Zlokovic’s lab who said that Zlokovic routinely pressured them to manipulate data. Two said they were told to discard notebooks with results that didn’t fit preferred conclusions he hoped to reach.

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“There were clear examples of him instructing people to manipulate data to fit the hypothesis,” one former employee told the journal.

The severity of the data manipulation charges merits a thorough investigation of Zlokovic’s data, said Elisabeth Bik, a microbiologist and scientific integrity consultant who co-wrote the whistleblower report.

“Appropriate steps would be for USC to ask Zlokovic to give them the lab’s notebooks and data,” Bik said. “For example, for images where it appears that certain parts might have been duplicated or erased, the original images as they came off a scanner or microscope need to be compared to the published figure panels.”

Bik is among a subset of the report’s authors who are considering filing a federal whistleblower lawsuit. Should the NIH deem that any federal grant money was used improperly, a successful suit would entitle the plaintiffs to a portion of the money the government can claw back.

Zlokovic has received roughly $93 million in NIH funding, according to Science. A spokesperson for NIH’s Office of Extramural Research would not comment on the specifics of the case.

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“We take concerns related to research integrity very seriously, and this may include allegations of research misconduct,” the office said in a statement.

Over the years, Zlokovic has created several biotech companies aimed at commercializing his scientific work. In 2007, he co-founded ZZ Biotech, which has been working to gain federal approval of 3K3A-APC.

Last year, Kent Pryor, ZZ Biotech’s chief executive, called the drug “a potential game-changer.”

“I believe, based on the positive clinical results to date, our 3K3A-APC will potentially create the first new drug class to treat ischemic stroke since 2003,” Pryor said.

On Tuesday, Pryor declined to comment on the details in the whistleblowers’ report. “I don’t want to get into particular explanations right now because of the ongoing investigations,” he said.

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He said the Phase III clinical trial had not yet begun.

Zlokovic is a leading researcher on the blood-brain barrier, with particular interest in its role in stroke and dementia. He received his medical degree and doctorate in physiology at the University of Belgrade and joined the faculty at USC’s Keck School of Medicine after several fellowships in London.

A polyglot and amateur opera singer, Zlokovic left USC and spent 11 years at the University of Rochester before returning in 2011. He was appointed director of USC’s Zilkha Neurogenetic Institute the following year.

“My role will be to enhance an already very strong neuroscience base and try to make USC the No. 1 place in the neurosciences in the country and the world,” Zlokovic said upon rejoining the USC faculty. “It’s a big goal, but I think, with what’s going on right now, it’s actually moving in that direction. I think that could be my greatest contribution.”

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There's a reason you can't stop doomscrolling through L.A.'s fire disaster

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There's a reason you can't stop doomscrolling through L.A.'s fire disaster

Even for those lucky enough to get out in time, or to live outside the evacuation zones, there has been no escape from the fires in the Los Angeles area this week.

There is hardly a vantage point in the city from which flames or plumes of smoke are not visible, nowhere the scent of burning memories can’t reach.

And on our screens — on seemingly every channel and social media feed and text thread and WhatsApp group — an endless carousel of images documents a level of fear, loss and grief that felt unimaginable here as recently as Tuesday morning.

Even in places of physical safety, many in Los Angeles are finding it difficult to look away from the worst of the destruction online.

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“To me it’s more comfortable to doomscroll than to sit and wait,” said Clara Sterling, who evacuated from her home Wednesday. “I would rather know exactly where the fire is going and where it’s headed than not know anything at all.”

A writer and comedian, Sterling is — by her own admission — extremely online. But the nature of this week’s fires make it particularly hard to disengage from news coverage and social media, experts said.

For one, there’s a material difference between scrolling through images of a far-off crisis and staying informed about an active disaster unfolding in your neighborhood, said Casey Fiesler, an associate professor specializing in tech ethics at the University of Colorado Boulder.

“It’s weird to even think of it as ‘doomscrolling,’ ” she said. “When you’re in it, you’re also looking for important information that can be really hard to get.”

When you share an identity with the victims of a traumatic event, you’re more likely both to seek out media coverage of the experience and to feel more distressed by the media you see, said Roxane Cohen Silver, distinguished professor of psychological science at UC Irvine.

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For Los Angeles residents, this week’s fires are affecting the people we identify with most intimately: family, friends and community members. They have consumed places and landmarks that feature prominently in fond memories and regular routines.

The ubiquitous images have also fueled painful memories for those who have lived through similar disasters — a group whose numbers have increased as wildfires have grown more frequent in California, Silver said.

This she knows personally: She evacuated from the Laguna Beach fires in 1993, and began a long-term study of that fire’s survivors days after returning to her home.

“Throughout California, throughout the West, throughout communities that have had wildfire experience, we are particularly primed and sensitized to that news,” she said. “And the more we immerse ourselves in that news, the more likely we are to experience distress.”

Absorption in these images of fire and ash can cause trauma of its own, said Jyoti Mishra, an associate professor of psychiatry at UC San Diego who studied the long-term psychological health of survivors of the 2018 Camp fire.

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The team identified lingering symptoms of post-traumatic stress disorder, depression and anxiety both among survivors who personally experienced fire-related trauma such as injury or property loss, and — to a smaller but still significant degree — among those who indirectly experienced the trauma as witnesses.

“If you’re witnessing [trauma] in the media, happening on the streets that you’ve lived on and walked on, and you can really put yourself in that place, then it can definitely be impactful,” said Mishra, who’s also co-director of the UC Climate Change and Mental Health Council. “Psychology and neuroscience research has shown that images and videos that generate a sense of personal meaning can have deep emotional impacts.”

The emotional pull of the videos and images on social media make it hard to look away, even as many find the information there much harder to trust.

Like many others, Sterling spent a lot of time online during the early days of the COVID-19 pandemic. Back then, Sterling said, the social media environment felt decidedly different.

“This time around I think I feel less informed about what’s going on because there’s been such a big push toward not fact-checking and getting rid of verified accounts,” she said.

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The rise of AI-generated images and photos has added another troubling kink, as Sterling highlighted in a video posted to TikTok early Thursday.

“The Hollywood sign was not on fire last night. Any video or photos that you saw of the Hollywood sign on fire were fake. They were AI generated,” she said, posting from a hotel in San Diego after evacuating.

Hunter Ditch, a producer and voice actor in Lake Balboa, raised similar concerns about the lack of accurate information. Some social media content she’s encountered seemed “very polarizing” or political, and some exaggerated the scope of the disaster or featured complete fabrications, such as that flaming Hollywood sign.

The spread of false information has added another layer of stress, she said. This week, she started turning to other types of app — like the disaster mapping app, Watch Duty — to track the spreading fires and changing evacuation zones.

But that made her wonder: “If I have to check a whole other app for accurate information, then what am I even doing on social media at all?”

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Pink Fire Retardant, a Dramatic Wildfire Weapon, Poses Its Own Dangers

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Pink Fire Retardant, a Dramatic Wildfire Weapon, Poses Its Own Dangers

From above the raging flames, these planes can unleash immense tankfuls of bright pink fire retardant in just 20 seconds. They have long been considered vital in the battle against wildfires.

But emerging research has shown that the millions of gallons of retardant sprayed on the landscape to tame wildfires each year come with a toxic burden, because they contain heavy metals and other chemicals that are harmful to human health and the environment.

The toxicity presents a stark dilemma. These tankers and their cargo are a powerful tool for taming deadly blazes. Yet as wildfires intensify and become more frequent in an era of climate change, firefighters are using them more often, and in the process releasing more harmful chemicals into the environment.

Some environmental groups have questioned the retardants’ effectiveness and potential for harm. The efficiency of fire retardant has been hard to measure, because it’s one of a barrage of firefighting tactics deployed in a major fire. After the flames are doused, it’s difficult to assign credit.

The frequency and severity of wildfires has grown in recent years, particularly in the western United States. Scientists have also found that fires across the region have become faster moving in recent decades.

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There are also the longer-term health effects of exposure to wildfire smoke, which can penetrate the lungs and heart, causing disease. A recent global survey of the health effects of air pollution caused by wildfires found that in the United States, exposure to wildfire smoke had increased by 77 percent since 2002. Globally, wildfire smoke has been estimated to be responsible for up to 675,000 premature deaths per year.

Fire retardants add to those health and environmental burdens because they present “a really, really thorny trade-off,” said Daniel McCurry, an assistant professor of civil and environmental engineering at the University of Southern California, who led the recent research on their heavy-metal content.

The United States Forest Service said on Thursday that nine large retardant-spraying planes, as well as 20 water-dropping helicopters, were being deployed to fight the Southern California fires, which have displaced tens of thousands of people. Several “water scooper” amphibious planes, capable of skimming the surface of the sea or other body of water to fill their tanks, are also being used.

Two large DC-10 aircraft, dubbed “Very Large Airtankers” and capable of delivering up to 9,400 gallons of retardant, were also set to join the fleet imminently, said Stanton Florea, a spokesman for the National Interagency Fire Center in Boise, Idaho, which coordinates national wildland firefighting efforts across the West.

Sprayed ahead of the fire, the retardants coat vegetation and prevent oxygen from allowing it to burn, Mr. Florea said. (Red dye is added so firefighters can see the retardant against the landscape.) And the retardant, typically made of salts like ammonium polyphosphate, “lasts longer. It doesn’t evaporate, like dropping water,” he said.

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The new research from Dr. McCurry and his colleagues found, however, that at least four different types of heavy metals in a common type of retardant used by firefighters exceeded California’s requirements for hazardous waste.

Federal data shows that more than 440 million gallons of retardant were applied to federal, state, and private land between 2009 and 2021. Using that figure, the researchers estimated that between 2009 and 2021, more than 400 tons of heavy metals were released into the environment from fire suppression, a third of that in Southern California.

Both the federal government and the retardant’s manufacturer, Perimeter Solutions, have disputed that analysis, saying the researchers had evaluated a different version of the retardant. Dan Green, a spokesman for Perimeter, said retardants used for aerial firefighting had passed “extensive testing to confirm they meet strict standards for aquatic and mammalian safety.”

Still, the findings help explain why concentrations of heavy metals tend to surge in rivers and streams after wildfires, sometimes by hundreds of times. And as scrutiny of fire suppressants has grown, the Forestry Service has set buffer zones surrounding lakes and rivers, though its own data shows retardant still inadvertently drifts into those waters.

In 2022, the environmental nonprofit Forest Service Employees for Environmental Ethics sued the government in federal court in Montana, demanding that the Forest Service obtain a permit under the Clean Water Act to cover accidental spraying into waterways.

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The judge ruled that the agency did indeed need to obtain a permit. But it allowed retardant use to continue to protect lives and property.

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2024 Brought the World to a Dangerous Warming Threshold. Now What?

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2024 Brought the World to a Dangerous Warming Threshold. Now What?

Source: Copernicus/ECMWF

Note: Temperature anomalies relative to 1850-1900 averages.

At the stroke of midnight on Dec. 31, Earth finished up its hottest year in recorded history, scientists said on Friday. The previous hottest year was 2023. And the next one will be upon us before long: By continuing to burn huge amounts of coal, oil and gas, humankind has all but guaranteed it.

The planet’s record-high average temperature last year reflected the weekslong, 104-degree-Fahrenheit spring heat waves that shuttered schools in Bangladesh and India. It reflected the effects of the bathtub-warm ocean waters that supercharged hurricanes in the Gulf of Mexico and cyclones in the Philippines. And it reflected the roasting summer and fall conditions that primed Los Angeles this week for the most destructive wildfires in its history.

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“We are facing a very new climate and new challenges, challenges that our society is not prepared for,” said Carlo Buontempo, director of the Copernicus Climate Change Service, the European Union monitoring agency.

But even within this progression of warmer years and ever-intensifying risks to homes, communities and the environment, 2024 stood out in another unwelcome way. According to Copernicus, it was the first year in which global temperatures averaged more than 1.5 degrees Celsius, or 2.7 degrees Fahrenheit, above those the planet experienced at the start of the industrial age.

For the past decade, the world has sought to avoid crossing this dangerous threshold. Nations enshrined the goal in the 2015 Paris agreement to fight climate change. “Keep 1.5 alive” was the mantra at United Nations summits.

Yet here we are. Global temperatures will fluctuate somewhat, as they always do, which is why scientists often look at warming averaged over longer periods, not just a single year.

But even by that standard, staying below 1.5 degrees looks increasingly unattainable, according to researchers who have run the numbers. Globally, despite hundreds of billions of dollars invested in clean-energy technologies, carbon dioxide emissions hit a record in 2024 and show no signs of dropping.

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One recent study published in the journal Nature concluded that the absolute best humanity can now hope for is around 1.6 degrees of warming. To achieve it, nations would need to start slashing emissions at a pace that would strain political, social and economic feasibility.

But what if we’d started earlier?

“It was guaranteed we’d get to this point where the gap between reality and the trajectory we needed for 1.5 degrees was so big it was ridiculous,” said David Victor, a professor of public policy at the University of California, San Diego.

The question now is what, if anything, should replace 1.5 as a lodestar for nations’ climate aspirations.

“These top-level goals are at best a compass,” Dr. Victor said. “They’re a reminder that if we don’t do more, we’re in for significant climate impacts.”

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The 1.5-degree threshold was never the difference between safety and ruin, between hope and despair. It was a number negotiated by governments trying to answer a big question: What’s the highest global temperature increase — and the associated level of dangers, whether heat waves or wildfires or melting glaciers — that our societies should strive to avoid?

The result, as codified in the Paris agreement, was that nations would aspire to hold warming to “well below” 2 degrees Celsius while “pursuing efforts” to limit it to 1.5 degrees.

Even at the time, some experts called the latter goal unrealistic, because it required such deep and rapid emissions cuts. Still, the United States, the European Union and other governments adopted it as a guidepost for climate policy.

Christoph Bertram, an associate research professor at the University of Maryland’s Center for Global Sustainability, said the urgency of the 1.5 target spurred companies of all kinds — automakers, cement manufacturers, electric utilities — to start thinking hard about what it would mean to zero out their emissions by midcentury. “I do think that has led to some serious action,” Dr. Bertram said.

But the high aspiration of the 1.5 target also exposed deep fault lines among nations.

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China and India never backed the goal, since it required them to curb their use of coal, gas and oil at a pace they said would hamstring their development. Rich countries that were struggling to cut their own emissions began choking off funding in the developing world for fossil-fuel projects that were economically beneficial. Some low-income countries felt it was deeply unfair to ask them to sacrifice for the climate given that it was wealthy nations — and not them — that had produced most of the greenhouse gases now warming the world.

“The 1.5-degree target has created a lot of tension between rich and poor countries,” said Vijaya Ramachandran, director for energy and development at the Breakthrough Institute, an environmental research organization.

Costa Samaras, an environmental-engineering professor at Carnegie Mellon University, compared the warming goals to health officials’ guidelines on, say, cholesterol. “We don’t set health targets on what’s realistic or what’s possible,” Dr. Samaras said. “We say, ‘This is what’s good for you. This is how you’re going to not get sick.’”

“If we were going to say, ‘Well, 1.5 is likely out of the question, let’s put it to 1.75,’ it gives people a false sense of assurance that 1.5 was not that important,” said Dr. Samaras, who helped shape U.S. climate policy from 2021 to 2024 in the White House Office of Science and Technology Policy. “It’s hugely important.”

Scientists convened by the United Nations have concluded that restricting warming to 1.5 degrees instead of 2 would spare tens of millions of people from being exposed to life-threatening heat waves, water shortages and coastal flooding. It might mean the difference between a world that has coral reefs and Arctic sea ice in the summer, and one that doesn’t.

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Each tiny increment of additional warming, whether it’s 1.6 degrees versus 1.5, or 1.7 versus 1.6, increases the risks. “Even if the world overshoots 1.5 degrees, and the chances of this happening are increasing every day, we must keep striving” to bring emissions to zero as soon as possible, said Inger Anderson, the executive director of the United Nations Environment Program.

Officially, the sun has not yet set on the 1.5 target. The Paris agreement remains in force, even as President-elect Donald J. Trump vows to withdraw the United States from it for a second time. At U.N. climate negotiations, talk of 1.5 has become more muted compared with years past. But it has hardly gone away.

“With appropriate measures, 1.5 Celsius is still achievable,” Cedric Schuster, the minister of natural resources and environment for the Pacific island nation of Samoa, said at last year’s summit in Azerbaijan. Countries should “rise to the occasion with new, highly ambitious” policies, he said.

To Dr. Victor of U.C. San Diego, it is strange but all too predictable that governments keep speaking this way about what appears to be an unachievable aim. “No major political leader who wants to be taken seriously on climate wants to stick their neck out and say, ‘1.5 degrees isn’t feasible. Let’s talk about more realistic goals,’” he said.

Still, the world will eventually need to have that discussion, Dr. Victor said. And it’s unclear how it will go.

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“It could be constructive, where we start asking, ‘How much warming are we really in for? And how do we deal with that?’” he said. “Or it could look very toxic, with a bunch of political finger pointing.”

Methodology

The second chart shows pathways for reducing carbon emissions that would have a 66 percent chance of limiting global warming this century to 1.5 degrees Celsius above the preindustrial average.

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