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Star USC scientist faces scrutiny — retracted papers and a paused drug trial

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Star USC scientist faces scrutiny — retracted papers and a paused drug trial

Late last year, a group of whistleblowers submitted a report to the National Institutes of Health that questioned the integrity of a celebrated USC neuroscientist’s research and the safety of an experimental stroke treatment his company was developing.

NIH has since paused clinical trials for 3K3A-APC, a stroke drug sponsored by ZZ Biotech, a Houston-based company co-founded by Berislav V. Zlokovic, professor and chair of the department of physiology and neuroscience at the Keck School of Medicine of USC.

Three of Zlokovic’s research papers have been retracted by the journal that published them because of problems with their data or images. Journals have issued corrections for seven more papers in which Zlokovic is the only common author, with one receiving a second correction after the new supplied data were found to have problems as well.

For an 11th paper co-authored by Zlokovic the journal Nature Medicine issued an expression of concern, a note journals append to articles when they have reason to believe there may be a problem with the paper but have not conclusively proven so. Since Zlokovic and his co-authors no longer had the original data for one of the questioned figures, the editors wrote, “[r]eaders are therefore alerted to interpret these results with caution.”

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“It’s quite unusual to see this volume of retractions, corrections and expressions of concern, especially in high-tier influential papers,” said Dr. Matthew Schrag, an assistant professor of neurology at Vanderbilt who co-authored the whistleblower report independently of his work at the university.

Both Zlokovic and representatives for USC declined to comment, citing an ongoing review initiated in the wake of the allegations, which were first reported in the journal Science.

“USC takes any allegations of research integrity very seriously,” the university said in a statement. “Consistent with federal regulations and USC policies, this review must be kept confidential.”

Zlokovic “remains committed to cooperating with and respecting that process, although it is unfortunately required due to allegations that are based on incorrect information and faulty premises,” his attorney Alfredo X. Jarrin wrote in an email.

Regarding the articles, “corrections and retractions are a normal and necessary part of the scientific post-publication process,” Jarrin wrote.

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Authors of the whistleblower report and academic integrity experts challenged that assertion.

“If these are honest errors, then the authors should be able to show the actual original data,” said Elisabeth Bik, a microbiologist and scientific integrity consultant who co-wrote the whistleblower report. “It is totally human to make errors, but there are a lot of errors found in these papers. And some of the findings are suggestive of image manipulation.”

Given the staid pace of academic publishing, publishing this many corrections and retractions only a few months after the initial concerns were raised “is, bizarrely, pretty quick,” said Ivan Oransky, co-founder of Retraction Watch.

The whistleblower report submitted to NIH identified allegedly doctored images and data in 35 research papers in which Zlokovic was the sole common author.

“There had been rumblings about things not being reproducible [in Zlokovic’s research] for quite some time,” Schrag said. “The real motivation to speak publicly is that some of his work reached a stage where it was being used to justify clinical trials. And I think that when you have data that may be unreliable as the foundation for that kind of an experiment, the stakes are just so much higher. You’re talking about patients who are often at the most vulnerable medical moment of their life.”

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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.

The drug is intended to minimize the bleeding and subsequent brain damage that can occur after an ischemic stroke, in which a blood clot forms in an artery leading to the brain.

In 2022, 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.

In Phase II of the trial, which was published in 2018 and called Rhapsody, six of the 66 patients who received 3K3A-APC died in the first week after their stroke, compared to one person among the 44 patients who got a placebo. Patients who received the drug also tended to report more disability 90 days after their stroke than those who got the placebo. The differences between the two groups were not statistically significant and could have been due to chance, and the death rate for patients in both groups evened out one month after the initial stroke.

“The statements that there is a risk in this trial is false,” said Patrick Lyden, a USC neurologist and stroke expert who was employed by Cedars-Sinai at the time of the trial. Zlokovic worked with Lyden as a co-investigator on the study.

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One correction has been issued to the paper describing the Phase II results, fixing an extra line in a data table that shifted some numbers to the wrong columns. “This mistake is mine. It’s not anybody else’s. I didn’t catch it in multiple readings,” Lyden said, adding that he noticed the error and was already working on the correction when the journal contacted him about it.

He disputed that the trial represented any undue risk to patients.

“I believe it’s safe, especially when you consider that the purpose of Rhapsody was to find a dose — the maximum dose — that was tolerated by the patients without risk, and the Rhapsody trial succeeded in doing that. We did not find any dose that was too high to limit proceeding to Phase III. It’s time to proceed with Phase III.”

Schrag stressed that the whistleblowers did not find evidence of manipulated data in the report from the Phase II trial. But given the errors and alleged data manipulation in Zlokovic’s earlier work, he said, it’s appropriate to scrutinize a clinical trial that would administer the product of his research to people in life-threatening situations.

In the Phase II data, “there’s a coherent pattern of [patient] outcomes trending in the wrong direction. There’s a signal in early mortality … there’s a trend toward worse disability numbers” for patients who received the drug instead of a placebo, he said.

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None are “conclusive proof of harm,” he said. But “when you’re seeing a red flag or a trend in the clinical trial, I would tend to give that more weight in the setting of serious ethical concerns around the pre-clinical data.”

The NIH paused the clinical trial in November, and it remains on hold, said Dr. Pooja Khatr, principal investigator of the NIH StrokeNet National Coordinating Center. Khatr declined to comment on the pause or the trial’s future, referring further questions to USC and NIH.

The NIH Office of Extramural Research declined to discuss Rhapsody or Zlokovic, citing confidentiality regarding grant deliberations.

ZZ Biotech Chief Executive Kent Pryor, who in 2022 called the drug “a potential game-changer,” said he had no comment or information on the halted trial.

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.

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A USC spokesperson confirmed that Zlokovic has retained his titles as department chair and director of the Zilkha institute.

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What’s in a Name? For These Snails, Legal Protection

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What’s in a Name? For These Snails, Legal Protection

The sun had barely risen over the Pacific Ocean when a small motorboat carrying a team of Indigenous artisans and Mexican biologists dropped anchor in a rocky cove near Bahías de Huatulco.

Mauro Habacuc Avendaño Luis, one of the craftsmen, was the first to wade to shore. With an agility belying his age, he struck out over the boulders exposed by low tide. Crouching on a slippery ledge pounded by surf, he reached inside a crevice between two rocks. There, lodged among the urchins, was a snail with a knobby gray shell the size of a walnut. The sight might not dazzle tourists who travel here to see humpback whales, but for Mr. Avendaño, 85, these drab little mollusks represent a way of life.

Marine snails in the genus Plicopurpura are sacred to the Mixtec people of Pinotepa de Don Luis, a small town in southwestern Oaxaca. Men like Mr. Avendaño have been sustainably “milking” them for radiant purple dye for at least 1,500 years. The color suffuses Mixtec textiles and spiritual beliefs. Called tixinda, it symbolizes fertility and death, as well as mythic ties between lunar cycles, women and the sea.

The future of these traditions — and the fate of the snails — are uncertain. The mollusks are subject to intense poaching pressure despite federal protections intended to protect them. Fishermen break them (and the other mollusks they eat) open and sell the meat to local restaurants. Tourists who comb the beaches pluck snails off the rocks and toss them aside.

A severe earthquake in 2020 thrust formerly submerged parts of their habitat above sea level, fatally tossing other mollusks in the snail’s food web to the air, and making once inaccessible places more available to poachers.

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Decades ago, dense clusters of snails the size of doorknobs were easy to find, according to Mr. Avendaño. “Full of snails,” he said, sweeping a calloused, violet-stained hand across the coves. Now, most of the snails he finds are small, just over an inch, and yield only a few milliliters of dye.

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Video: This Parrot Has No Beak, But Is at the Top of the Pecking Order

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Video: This Parrot Has No Beak, But Is at the Top of the Pecking Order

new video loaded: This Parrot Has No Beak, But Is at the Top of the Pecking Order

Bruce, a disabled kea parrot, is missing his top beak. The bird uses tools to keep himself healthy and developed a jousting technique that has made him the alpha male of his group.

By Meg Felling and Carl Zimmer

April 20, 2026

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Contributor: Focus on the real causes of the shortage in hormone treatments

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Contributor: Focus on the real causes of the shortage in hormone treatments

For months now, menopausal women across the U.S. have been unable to fill prescriptions for the estradiol patch, a long-established and safe hormone treatment. The news media has whipped up a frenzy over this scarcity, warning of a long-lasting nationwide shortage. The problem is real — but the explanations in the media coverage miss the mark. Real solutions depend on an accurate understanding of the causes.

Reporters, pharmaceutical companies and even some doctors have blamed women for causing the shortage, saying they were inspired by a “menopause moment” that has driven unprecedented demand. Such framing does a dangerous disservice to essential health advocacy.

In this narrative, there has been unprecedented demand, and it is explained in part by the Food and Drug Administration’s recent removal of the “black-box warning” from estradiol patches’ packaging. That inaccurate (and, quite frankly, terrifying) label had been required since a 2002 announcement overstated the link between certain menopause hormone treatments and breast cancer. Right-sizing and rewording the warning was long overdue. But the trouble with this narrative is that even after the black-box warning was removed, there has not been unprecedented demand.

Around 40% of menopausal women were prescribed hormone treatments in some form before the 2002 announcement. Use plummeted in its aftermath, dipping to less than 5% in 2020 and just 1.8% in 2024. According to the most recent data, the number has now settled back at the 5% mark. Unprecedented? Hardly. Modest at best.

Nor is estradiol a new or complex drug; the patch formulation has existed for decades, and generic versions are widely manufactured. There is no exotic ingredient, no rare supply chain dependency, no fluke that explains why women are suddenly being told their pharmacy is out of stock month after month.

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The story is far more an indictment of the broken insurance industry: market concentration, perverse incentives and the consequences of allowing insurance companies to own the pharmacy benefit managers that effectively control drug access for the majority of users. Three companies — CVS Caremark, Express Scripts and OptumRx — manage 79% of all prescription drug claims in the United States. Those companies are wholly owned subsidiaries of three insurance behemoths: CVS Health, Cigna and UnitedHealth Group, respectively. This means that the same corporation that sells you your insurance plan also decides which drugs get covered, at what price, and whether your pharmacy can stock them. This is called vertical integration. In another era, we might have called it a cartel. The resulting problems are not unique to hormone treatments; they have affected widely used medications including blood thinners, inhalers and antibiotics. When a low-cost generic such as estradiol — a medication with no blockbuster profit margins and no patent protection — runs into friction in this system, the friction is not random. It is structural. Every decision in that chain is filtered through the same corporate profit motive. And when the drug in question is an off-patent estradiol patch that has negligible profit margins because of generic competition but requires logistical investment to keep consistently in stock? The math on “how much does this company care about ensuring access” is not complicated.

Unfortunately, there is little financial incentive to ensure smooth, consistent access. There is, however, significant financial incentive to steer patients toward branded alternatives, or simply to let supply tighten — because the companies aren’t losing much profit if sales of that product dwindle. This is not a conspiracy theory: The Federal Trade Commission noted this dynamic in a report that documented how pharmacy benefit managers’ practices inflate costs, reduce competition and harm patient access, particularly for independent pharmacies and for generic drugs.

Any claim that the estradiol patch shortage is meaningfully caused by more women now demanding hormone treatments is a distraction. It is also misogyny, pure and simple, to imply that the solution to the shortage is for women’s health advocates to dial it down and for women to temper their expectations. The scarcity of estradiol patches is the outcome of a broken system refusing to provide adequate supply.

Meanwhile, there are a few strategies to cope.

  • Ask your prescriber about alternatives. Estradiol is available in multiple formulations, including gel, spray, cream, oral tablet, vaginal ring and weekly transdermal patch, which is a different product from the twice-weekly patch and may be more consistently available depending on manufacturer and region.
  • Consider an online pharmacy. Many are doing a good job locating and filling these prescriptions from outside the pharmacy benefit manager system.
  • Call ahead. Patch shortages are inconsistent across regions and distributors. A call to pharmacies in your area, or a broader geographic radius if you’re able, can locate stock that your regular pharmacy doesn’t have.
  • Consider a compounding pharmacy. These sources can sometimes meet needs when commercially manufactured products are inaccessible. The hormones used are the same FDA-regulated bulk ingredients.

Beyond those Band-Aid solutions, more Americans need to fight for systemic change. The FTC report exists because Congress asked for it and committed to legislation that will address at least some of the problems. The FDA took action to change the labeling on estrogen in the face of citizen and medical experts’ pressure; it should do more now to demand transparency from patch manufacturers.

Most importantly, it is on all of us to call out the cracks in the current system. Instead of repeating “there’s a patch shortage” or a “surge in demand,” say that a shockingly small minority of menopausal women still even get hormonal treatments prescribed at all, and three drug companies control the vast majority of claims in this country. Those are the real problems that need real solutions.

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Jennifer Weiss-Wolf, the executive director of the Birnbaum Women’s Leadership Center at New York University School of Law, is the author of the forthcoming book When in Menopause: A User’s Manual & Citizen’s Guide. Suzanne Gilberg, an obstetrician and gynecologist in Los Angeles, is the author of “Menopause Bootcamp.”

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