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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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Q&A: Learn how Olympians keep their cool from Team USA's chief sports psychologist

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Q&A: Learn how Olympians keep their cool from Team USA's chief sports psychologist

Your morning jog or weekly basketball game may not take place on an Olympic stage, but you can use Team USA’s techniques to get the most out of your exercise routine.

It’s not all about strength and speed. Mental fitness can be just as important as physical fitness.

That’s why the U.S. Olympic & Paralympic Committee created a psychological services squad to support the mental health and mental performance of athletes representing the Stars and Stripes.

“I think happy, healthy athletes are going to perform at their best, so that’s what we’re striving for,” said Jessica Bartley, senior director of the 15-member unit.

Bartley studied sports psychology and mental health after an injury ended her soccer career. She joined the USOPC in 2020 and is now in Paris with Team USA’s 592 competitors, who range in age from 16 to 59.

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Bartley spoke with The Times about how her crew keeps Olympic athletes in top psychological shape, and what the rest of us can learn from them. Her comments have been edited for length and clarity.

Why is exercise good for mental health?

It gets you moving. It gets the endorphins going. And there’s often a lot of social aspects that are really helpful.

There are a number of sports that stretch your brain in ways that can be really, really valuable. You’re thinking about hand-eye coordination, or you’re thinking about strategy. It can improve memory, concentration, even critical thinking.

What’s the best way to get in the zone when it’s time to compete?

When I work with athletes, I like to understand what their zone is. If a 0 or a 1 is you’re totally chilled out and a 10 is you’re jumping around, where do you need to be? What’s your number?

People will say, “I’m at a 10 and I need to be at an 8 or a 7.” So we’ll talk about ways of bringing it down, whether it’s taking a deep breath, listening to relaxing music, or talking to your coach. Or there’s times when people say they need to be more amped up. That’s when you see somebody hitting their chest, or jumping up and down.

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If you make a mistake in the middle of a competition, how do you move on instead of dwelling on it?

I often teach athletes a reset routine. I played goalie, so I had a lot of time to think after getting scored on. I would undo my goalie gloves and put them back on, which to me was a reset. I would also wear an extra hairband on my wrist, and when I would snap it, that meant I needed to get out of my head.

It’s not just a physical reset — it helps with a mental reset. If you do the same thing every single time, it goes through the same neural pathway to where it’s going to reset the brain. That can be really impactful.

Do Olympic athletes have to deal with burnout?

Oh, yeah. Everybody has a day where they don’t want to do whatever it is. That’s when you have to ask, “What’s in my best interests? Do I need a recovery day, or do I really need to get in the pool, or get in the gym?”

Sometimes you really do need what we like to refer to as a mental health day.

How can you psych yourself up for a workout when you just aren’t feeling it?

It’s really helpful to think about why you’re doing this and why you’re pushing yourself. Do you have goals related to an activity or sport? Is there something tied to values around hard work or discipline, loyalty or dependability?

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When you don’t want to get in the gym, when you don’t want to go for a run, think about something bigger. Tie it back to values.

Is sleep important for maintaining mental health?

Yes! We started doing mental health screens with athletes before the Tokyo Games. We asked about depression, anxiety, disordered eating and body image, drugs and alcohol, and sleep. Sleep was actually our No. 1 issue. It’s been a huge initiative for us.

How much sleep should we be getting?

It’s different for everyone, but generally we know seven to nine hours of sleep is good. Sometimes some of these athletes need 10 hours.

I highly recommend as much sleep as you need. If you didn’t get enough sleep, napping can be really valuable.

Is napping just for Olympic athletes or is it good for everybody?

Everybody! Naps are amazing.

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What if there’s no time for a nap?

There are different ways of recharging. Naps could be one of them, but maybe you just need to get off your feet for 20 minutes. Maybe you need to do a meditation or mindfulness exercise and just close your eyes for five minutes.

How do you minimize the effects of jet lag?

We try to shift one hour per day. That’s the standard way of doing it. If you can, it’s super helpful. But it’s not always possible.

The thing we tell athletes is that our bodies are incredible, and you will even things out if you can get back on schedule. One or two nights of crummy sleep is not going to impact your overall performance.

What advice do you give athletes who have trouble falling asleep the night before a competition?

You don’t want to change much right before a competition, so I usually direct athletes to do what they would normally do.

Do you need to unwind by reading a book? Do you need to talk on the phone with somebody and get your mind off things? Can you put your mind in a really restful place and think about things that are really relaxing?

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Are there any mindfulness or meditation exercises that you find helpful?

There are some athletes who benefit greatly from an hourlong meditation. I love something quick, something to reset my brain, maybe close my eyes for a minute.

If I’m feeling like I need to take a moment, I love mindful eating. You savor a bite and go, “Oh, my gosh, I have not been fully engaged with my senses today.” Or you could take a mindful walk and take in the sights, the smells, all of the things that are around you.

What do you eat when you need a quick nutrition boost?

Cashews. I tend to carry those with me. They’ve got enough energy to make sure I keep going, physically.

I’ve always got gummy bears on me too. There’s no nutritional value but they keep me going mentally. I’m a big proponent of both.

Is it OK to be superstitious in sports?

It depends how flexible you are. Maybe you put on your socks or shoes a certain way, or listen to certain music. Routines are really soothing. They set your brain up for success in a particular performance. It can be really, really helpful.

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But I’ve also seen an athlete forget their lucky underwear or their lucky socks, and they’re all out of sorts. So your routine has to be flexible enough that you’re not going to completely fall apart if you don’t do it exactly.

Are Olympians made of stronger psychological stuff than the rest of us?

Not necessarily. There are some who don’t get feathers ruffled and have a high tolerance for the fanfare. There’s also a lot of regular human beings who just happen to be fantastic at a particular activity.

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‘Ready, Steady, Slow’: Championship Snail Racing at 0.006 M.P.H.

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‘Ready, Steady, Slow’: Championship Snail Racing at 0.006 M.P.H.
For the next few weeks, Paris will be home to many of the world’s impressive athletes, including some of the fastest human beings on the planet. Among the competitors gathering for the Olympic Games are runners who can knock out a marathon in just over two hours, a mile in under four minutes and 100 meters in less than 10 seconds.

Earlier this month, the rural village of Congham, England, played host to a less likely group of athletes: dozens of garden snails. They had gathered to compete in the World Snail Racing Championships, where the world record time for completing the 13.5 inch course stands at 2 minutes flat. At that speed — roughly 0.006 miles per hour — it would take the snails more than six days to travel a mile.

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Caring for condor triplets! Record 17 chicks thrive at L.A. Zoo under surrogacy method

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Caring for condor triplets! Record 17 chicks thrive at L.A. Zoo under surrogacy method

A new method of rearing California condors at the Los Angeles Zoo has resulted in a record-breaking 17 chicks hatched this year, the zoo announced Wednesday.

All of the newborn birds will eventually be considered for release into the wild under the U.S. Fish and Wildlife Service’s California Condor Recovery Program, a zoo spokesperson said.

“What we are seeing now are the benefits of new breeding and rearing techniques developed and implemented by our team,” zoo bird curator Rose Legato said in a statement. “The result is more condor chicks in the program and ultimately more condors in the wild.”

Breeding pairs of California condors live at the zoo in structures the staff “affectionately calls condor-miniums,” spokesperson Carl Myers said. When a female produces a fertilized egg, the egg is moved to an incubator. As its hatching approaches, the egg is placed with a surrogate parent capable of rearing the chick.

California condor eggs are cared for at L.A. Zoo. The animal is critically endangered.

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(Jamie Pham / L.A. Zoo)

This bumper year of condor babies is the result of a modification to a rearing technique pioneered at the L.A. Zoo.

Previously, when the zoo found itself with more fertilized eggs than surrogate adults available, staff raised the young birds by hand. But condors raised by human caretakers have a lower chance of survival in the wild (hence the condor puppets that zookeepers used in the 1980s to prevent young birds from imprinting on human caregivers).

In 2017, the L.A. Zoo experimented with giving an adult bird named Anyapa two eggs instead of one. The gamble was a success. Both birds were successfully released into the wild.

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Faced with a large number of eggs this year, “the keepers thought, ‘Let’s try three,’” Myers said. “And it worked.”

The zoo’s condor mentors this season ultimately were able to rear three single chicks, eight chicks in double broods and six chicks in triple broods. The previous record number of 15 chicks was set in 1997.

Condor experts applauded the new strategy.

“Condors are social animals and we are learning more every year about their social dynamics. So I’m not surprised that these chick-rearing techniques are paying off,” said Jonathan C. Hall, a wildlife ecologist at Eastern Michigan University. “I would expect chicks raised this way to do well in the wild.”

The largest land bird in North America with an impressive wingspan up to 9½ feet, the California condor could once be found across the continent. Its numbers began to decline in the 19th century as human settlers with modern weapons moved into the birds’ territory. The scavenger species was both hunted by humans and inadvertently poisoned by lead bullet fragments embedded in carcasses it ate. The federal government listed the birds as an endangered species in 1967.

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A condor, one of a record-breaking 17 at the zoo, makes its way out of its shell.

A condor, one of a record-breaking 17 at the zoo, makes its way out of its shell.

(Jamie Pham / L.A. Zoo)

When the California Condor Recovery Program began four decades ago, there were only 22 California condors left on Earth. As of December, there were 561 living individuals, with 344 of those in the wild. Despite the program’s success in raising the population’s numbers, the species remains critically endangered.

In addition to the ongoing threat of lead poisoning, the large birds are also at risk from other toxins. One 2022 study found more than 40 DDT-related compounds in the blood of wild California condors — chemicals that had made their way from contaminated marine life to the top of the food chain.

“Despite our success in returning condors to the wild, free-flying condors continue to face many obstacles with lead poisoning being the No. 1 cause of mortality,” said Joanna Gilkeson, spokesperson for Fish and Wildlife’s Pacific Southwest Region. “Innovative strategies, like those the L.A. Zoo is implementing, help us to produce more healthy chicks and continue releasing condors into the wild.”

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The chicks will remain in the zoo’s care for the next year and a half before they are evaluated for potential release to the wild. Thus far, the zoo has contributed 250 condor chicks to Fish and Wildlife’s program, some of which the agency has redeployed to other zoos as part of its conservation efforts.

In a paper published earlier this year, a team of researchers found that birds born in captivity have slightly lower survival rates for their first year or two but then have equally successful outcomes to wild-hatched birds.

“Because condors reproduce slowly, releases of captive-bred birds are essential to the recovery of the species, especially in light of ongoing losses due to lead-related mortality,” said Victoria Bakker, a quantitative ecologist at Montana State University and lead author of the paper. “The team at the L.A. Zoo should be recognized for their innovative and important contributions to condor recovery.”

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