STAT+: At AACR, a provocative use of CAR-T, Merck’s new thing and cancer’s geography problem

You’re reading the web version of STAT’s popup newsletter, AACR in 30 seconds, your guide to what’s happening at the American Association of Cancer Researchers’ annual meeting. Sign up here.

We’re back with more data from the AACR meeting! Among the highlights today: a first look at a drug Merck acquired from China, a fascinating but potentially controversial use for CAR-T, and American oncology’s geography problem. Don’t forget: Tuesday night we will host a live event in San Diego, and we also have a virtual recap of the AACR conference on Thursday.

CAR-T shows deep response in smoldering myeloma

In an early phase trial, investigators at Dana-Farber Cancer Institute treated 20 high risk smoldering multiple myeloma patients with Carvykti, a BCMA directed CAR-T therapy. The idea was to use the immunotherapy on patients with the multiple myeloma precursor condition, hoping to prevent the active cancer in patients at high risk of progression.

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Safe@Campus Virtual Reality Training for Campus Shooting Preparedness: Prototype Development and Usability Study

<strong>Background:</strong> Campus shootings, though infrequent, result in significant loss of life, psychological trauma, and disruption to university communities. Traditional preparedness programs developed for K-12 settings do not translate well to university environments. Virtual reality (VR) offers an immersive and engaging method to enhance situational awareness and decision-making during high-stress events. <strong>Objective:</strong> This study aimed to develop the Safe@Campus prototype, a theory-informed, stakeholder-engaged VR-based prototype designed to prepare university students to recognize and respond to campus shooting threats, and to evaluate its initial usability and feasibility among undergraduate students. <strong>Methods:</strong> We followed a 2-phase, user-centered design process. Phase I (stakeholder-informed feasibility assessment and prototype refinement): through interviews with campus safety experts, firearm safety practitioners, school safety specialists, and students, we identified key content, scenario requirements, and implementation considerations. A 360-degree video–based VR prototype depicting an active shooter incident in a university classroom was developed using Unity3D, incorporating branching decision points aligned with the “run, hide, or fight” framework. Expert and user feedback guided iterative refinements. Phase II (student usability and acceptability testing): 2 focus groups with undergraduates at The Ohio State University (N=17) viewed a VR scenario and then participated in guided discussions about prior training experiences, the acceptability of VR, and recommendations for improvement. Transcripts were analyzed using constant comparative methods in ATLAS.ti (version 25). <strong>Results:</strong> The first focus group comprised 8 students (n=5, 63% female; n=3, 38% White, n=4, 50% Asian/Asian American), and the second comprised 9 students (n=6, 67% female; n=6, 67% White). Across both groups, 82% (14/17) reported participating in active shooter drills during K-12 schooling, yet many felt these experiences did not adequately prepare them for the complexity of university environments. The following four major themes emerged: (1) prior experience with active shooter drills: K-12 drills varied widely in realism and left students uncertain about appropriate actions in university settings; (2) need for university-specific training: participants noted substantial gaps in preparedness and expressed strong support for required, standardized training; (3) perceived usefulness of VR: students found VR highly engaging, realistic, and effective for reinforcing situational awareness and decision-making; and (4) recommendations for prototype improvement: students suggested increasing interactivity, adding time-pressured decisions, expanding scenarios to diverse campus spaces, and integrating the program into required university activities such as orientation. <strong>Conclusions:</strong> Safe@Campus is a feasible, acceptable, and engaging VR-based approach to campus shooting preparedness. Students viewed the immersive, decision-driven format as an effective way to build practical skills not addressed by traditional training. Future development should expand scenario diversity, increase interactivity, and evaluate program effectiveness in larger trials. <strong>Trial Registration:</strong>

STAT+: In early trial, CAR-T results raise hope of preventing multiple myeloma in high-risk patients

SAN DIEGO — Alison Cameron spent close to a decade fighting to keep her myeloma under control. She’d been diagnosed with smoldering multiple myeloma, a precursor to cancer, and received infusions to keep it from progressing to active multiple myeloma for years. Now, after receiving CAR-T therapy, an aggressive immunotherapy, while on a trial, the 54-year old anesthesiologist is hoping the risk of cancer is gone for good.

It’s a reasonable hope, given the results of that trial, which researchers presented at the American Association for Cancer Research meeting here on Monday. All 20 patients who received the trial treatment no longer had any detectable myeloma cells in their body. That’s a far deeper and more complete response than scientists typically expect when it comes to multiple myeloma, and it’s prompting some experts to consider the possibility these patients have truly had active cancer permanently averted.

Currently, there is only one approved therapy for high risk smoldering myeloma, an antibody therapy called Darzalex. Patients can remain on treatment for years, but without achieving these kinds of deep molecular responses, and many still progress within five years, said Ecaterina Dumbrava, a cancer researcher at MD Anderson Cancer Center who did not work on the study. “The results raise a very important question: Whether early immune interception can not only delay progression but redefine treatment goals? Can we talk about the word we always avoid, which is cure?” she said.

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Lilly to Acquire Kelonia for Up to $7B, Expanding Cancer Cell Therapy Pipeline

Eli Lilly has agreed to acquire Kelonia Therapeutics for up to $7 billion, the companies said today, in a deal that would bolster the buyer’s oncology pipeline with an early clinical phase lentiviral in vivo chimeric antigen receptor T-cell (CAR T) therapy under study in relapsed/refractory multiple myeloma.

Kelonia’s lead program KLN-1010 is a one-time intravenous gene therapy designed to generate anti-B-cell maturation antigen (BCMA) CAR T cells, targeting the BCMA protein expressed on the surface of multiple myeloma cells.

In December at the American Society of Hematology (ASH) 2025 Annual Meeting, Kelonia presented positive early clinical data for KLN-1010 from the Phase I inMMyCARTM trial (NCT07075185). The data showed the CAR T therapy to have 100% minimal residual disease (MRD)-negative response rate across four patients, all of whom remained in response through the longest follow up of five months.

Those and other results, according to the company, provided initial clinical validation of KLN-1010 and demonstrated promising tolerability. In January, Kelonia won FDA clearance for an investigational new drug (IND) application for KLN-1010, enabling the trial to expand from Australia into multiple clinical sites across the United States.

“The early clinical data for KLN-1010 are highly encouraging, both as a potential step forward for patients with multiple myeloma and as proof of concept for Kelonia’s platform,” Jacob Van Naarden, executive vice president and president of Lilly Oncology and head of corporate business development, said in a statement.

Investors appeared more sanguine about the Kelonia acquisition as Lilly shares were all but flat in early Monday trading as of 11 a.m. ET, to $927.16 from Friday’s close of $927.03. Kelonia is privately held.

KLN-1010 applies the company’s in vivo gene placement system (iGPS®), which uses engineered lentiviral-based particles designed to efficiently and selectively enter T-cells inside the body, enabling a patient’s own body to generate CAR T therapies designed to treat underlying disease.

Lilly and Kelonia reason that KLN-1010 could transform treatment of multiple myeloma by eliminating challenges associated with both ex vivo patient-specific cell therapy manufacturing, and pre-administration chemotherapy.

“Autologous CAR T therapies have meaningfully improved outcomes for patients with various cancers, but significant manufacturing, safety, and access barriers mean that only a fraction of eligible patients actually receive them,” Van Naarden added. “Kelonia’s in vivo platform has the potential to change that by delivering rapid, durable responses in a far simpler, off-the-shelf format.”

Kelonia marks Eli Lilly’s fourth announced acquisition of a smaller biotech this year:

Behind the deals

Behind all the deals is the pharma giant’s desire to capitalize on the billions of dollars it is generating from sales of its obesity and diabetes drugs based on glucagon-like peptide 1 (GLP-1) receptor analysts alone or in tandem with a glucose-dependent insulinotropic polypeptide (GIP). Lilly markets tirzepatide, a GLP-1/GIP dual agonist, in obesity as Zepbound® ($13.542 billion in 2025 sales) and in diabetes as Mounjaro® ($22.965 billion).

Lilly stands to generate even more in obesity-related sales in coming years once it brings to market its oral obesity drug Foundayo™ (orforglipron), a small molecule GLP-1 receptor agonist—though analysts predict the drug’s 2026 sales will likely be lower than once expected because of the price war Foundayo faces competing head to head with Lilly’s arch-rival in obesity drugs, Novo Nordisk. In December, Novo Nordisk got a jump on Lilly when the Danish biotech giant won FDA approval for oral Wegovy® (semaglutide), a once-daily 25 mg GLP-1 receptor agonist tablet indicated for chronic weight management.

A Lilly buyout of Kelonia could compel Johnson & Johnson to take a closer look at acquiring Legend Biotech, Kostas Biliouris, PhD, a managing director on the biotechnology research team of Oppenheimer, wrote Sunday in a research note. He cited the fact J&J’s Janssen Biotech successfully partnered with Legend to develop Carvykti® (ciltacabtagene autoleucel), a B-cell maturation antigen (BCMA)-directed CAR T-cell therapy indicated for adults with relapsed or refractory multiple myeloma who have received at least one prior line of therapy. Carvykti generated $1.877 billion in sales last year, up nearly double (96%) from $963 million in 2024.

Also, Biliouris cited the presence in Legend’s pipeline of LUCAR-G39D, a clinical in vivo CAR T program designed to treat B-cell non-Hodgkin’s lymphoma by targeting CD19xCD20. LUCAR-G39D showed positive first-in-human safety and efficacy data from a Phase I trial (NCT06395870) at ASH last December.

“We believe in vivo CAR T technology has strong potential, as treatment process is fast and circumvents the need for lymphodepletion, but think it will likely take ~6-8years before safety/durability questions are addressed, and regulatory approval is granted,” Biliouris predicted.

Lilly has agreed to acquire Kelonia for $3.25 billion upfront plus up to $3.75 billion in future payments tied to achieving specified clinical, regulatory, and commercial milestones. The acquisition deal is subject to regulatory approvals and other customary closing conditions, and is expected to close in the second half of 2026.

Upon closing, Lilly said, it will determine how to account for the transaction in accordance with Generally Accepted Accounting Principles (GAAP), then reflect the deal in future financial results and financial guidance.

“Kelonia’s leadership in advancing the immense promise of in vivo cell therapy is unmatched, extending its reach and impact beyond the traditional boundaries of personalized medicine,” Kelonia CEO Kevin Friedman, PhD, stated. “We have demonstrated the ability to achieve deep multiple myeloma remissions with significantly reduced complexity and cost relative to ex vivo CAR T-cell approaches.”

“In combination with Lilly’s strengths, our in vivo iGPS platform is positioned to broaden the reach of cell therapy beyond the current CAR T landscape in hematologic malignancies and to transform treatment across a far wider range of cancers and other serious diseases,” Friedman added.

The post Lilly to Acquire Kelonia for Up to $7B, Expanding Cancer Cell Therapy Pipeline appeared first on GEN – Genetic Engineering and Biotechnology News.

Distinct Nature of Parkinson’s Disease Gut Microbiome Identified

Research led by University College London has characterized a specific gut microbiome signature found in people with Parkinson’s disease.

Writing in Nature Medicine, the researchers also found that people carrying a genetic mutation in the GBA1 gene that put them at risk of developing Parkinson’s disease had gut microbiomes similar to people with the condition.

Parkinson’s is the second most common neurodegenerative disease in the U.S. after Alzheimer’s disease affecting more than one million people across the country. By the time full-blown motor symptoms emerge, a large degree of neurological damage has already occurred, so much work is underway to find ways to predict and diagnose early disease, as well as to develop more effective treatments.

“In recent years there has been a growing recognition of the links between Parkinson’s disease—a brain disorder—and gut health,” said co-lead author Anthony Schapira, MD, a professor at UCL Queen Square Institute of Neurology, in a press statement.

“Here we have strengthened that evidence and shown that microbes in the gut can reveal signs of Parkinson’s and may be an early warning signal… years before symptom onset.”

For this study, the researchers evaluated gut microbiome samples from 271 Parkinson’s disease patients, 43 people carrying GBA1 risk variants who did not yet have disease symptoms and 150 healthy controls. They also validated their findings in a further 638 people with Parkinson’s and 319 healthy controls from the U.K., Korea, and Turkey.

Schapira and team used DNA sequencing to see which bacterial species were present in each person’s gut. Comparing people with Parkinson’s disease to healthy controls, they found 176 bacterial species that were more or less common in people with the condition.

For example, people with Parkinson’s had more potentially pro‑inflammatory bacteria, including Bifidobacterium longum and B. dentium, Streptococcus mutans, and Lactobacillus paragasseri, than healthy controls.

In contrast, healthy controls had more helpful, butyrate‑producing gut bacteria from including Roseburia intestinalis, R. inulinivorans and some Faecalibacterium species and less pro-inflammatory species.

Notably, people in the at-risk group who carried a GBA1 risk variant had a gut microbiome somewhere between healthy controls and people with Parkinson’s, suggesting that the composition of microbes in the gut may change over time as the disease develops. In this group, 142 of the 176 species that differed in people with Parkinson’s versus healthy controls also showed changed abundance.

“For the first time we identify bacteria in the gut of people with Parkinson’s that can also be found in those with a genetic risk for the disease, but before they develop symptoms. Importantly, these same changes can be found in a small proportion of the general population that may put them at increased risk for Parkinson’s,” said Schapira.

“This discovery opens the way not only to see if the bacteria are a way to identify those at risk of Parkinson’s, but also to see if changing the bacterial population, through dietary changes or medication, can reduce a person’s risk for Parkinson’s.”

The post Distinct Nature of Parkinson’s Disease Gut Microbiome Identified appeared first on Inside Precision Medicine.

AACR 2026: Cancers of Unknown Primary Identified by DNA Methylation AI Model

SAN DIEGO – Researchers from Kindai University in Japan have developed a machine learning model that accurately predicts the origin of diverse cancer types in patients with cancers of unknown primary (CUP) by analyzing CpG-based DNA methylation. Results showed that the model correctly identified the cancer type in about 95% of cases in the test cohort, and achieved 87% accuracy when applied to an independent validation cohort from 31 cases representing 17 different cancer types. The work was presented at the American Association for Cancer Research (AACR) Annual Meeting.  

“Our findings suggest that DNA-based approaches can help identify where a cancer may have started, even when the original tumor is not visible,” said Marco A. De Velasco, PhD, a faculty member in the department of genome biology at Kindai University in Japan.  

CUP are metastatic malignancies in which the primary cancer site could not be identified. These cancers are often associated with poorer outcomes, as patients are typically treated with broad, nonspecific chemotherapy regimens rather than therapies targeted to a specific cancer type. 

Approximately only 15-20% of patients with CUP show features that allow site-specific therapies. Patients receiving site-directed therapy can survive up to 24 months, compared with six to nine months for those receiving standard treatment. 

Patterns in tumor biology, such as gene activity or chemical modifications to DNA, can differ between cancer types and persist even after the cancer has spread and guide development of these therapies. While some methods have shown promise, they have yet to demonstrate clear survival benefits in clinical trials. 

The model was developed using methylation data from nearly 7,500 patients with 21 different cancer types obtained from The Cancer Genome Atlas Program and other public datasets. Using machine learning, the researchers identified CpG methylation and built methylation profiles that were associated with different tumor types. 

Del Velasco emphasized that the study achieved high accuracy in predicting the origin of diverse cancer types using a small subset of DNA markers, about 1,000 CpG regions selected from hundreds of thousands across the genome. “This is important because it shows that we can simplify complex molecular data while still maintaining strong predictive performance,” he said. 

As a limitation, the model was developed using cancers with known origins, rather than true CUP. Testing in CUP patients is important to understand how well the model performs in clinical settings. Additionally, not all tumors are easily accessible for genetic testing, particularly tumors in advanced stage. Looking ahead, the authors aim to adapt and evaluate the model using blood-based biopsy to analyze circulating tumor DNA instead of relying on DNA from tissue samples. 

The post AACR 2026: Cancers of Unknown Primary Identified by DNA Methylation AI Model appeared first on GEN – Genetic Engineering and Biotechnology News.

Decoding Resistance to Targeted Therapy via New Cancer Models

ATCC and the Broad Institute report the development of engineered isogenic cancer models designed to replicate resistance to targeted therapies, beginning with osimertinib, the latest-generation epidermal growth factor receptor (EGFR) inhibitor used to treat non-small cell lung cancer (NSCLC) with EGFR mutations.

According to the researchers, the work addresses a critical challenge in oncology—treatment resistance that emerges over time. EGFR-mutant lung cancer was among the first subsets of a major epithelial cancer where directly targeting an oncogene was associated with marked clinical benefit. While targeted therapies have significantly improved overall survival, resistance inevitably develops.

cancer drug resistance
Understanding resistance mechanisms is essential for identifying combination therapies capable of producing durable responses and potentially disease-free remissions. [Planet Flem/Getty Images]

Developing resistant models directly from patient tumors can take years due to the scarcity of samples. In contrast, engineering resistance mechanisms in controlled laboratory models allows researchers to systematically study multiple escape pathways much faster.

To accelerate discovery, scientists from ATCC and the Broad Institute collaborated to engineer a panel of drug-resistant NSCLC models using CRISPR gene editing and gene overexpression techniques. These models systematically model the resistance mechanisms that arise in patients treated with osimertinib, note the researchers.

“With this powerful new set of tools, drug-sensitive and drug-resistant cancer cells can be studied side by side to understand therapeutic resistance and the underlying drivers,” says Roth Cheng, PhD, CEO of ATCC. “By creating and providing these cancer models along with a rich data-set to the global research community, our hope is to reveal hidden targets and combination strategies that turn today’s treatment failures into tomorrow’s breakthrough. We look forward to extending this approach to additional cancer types.”

Engineering drug-resistant lung cancer models

Led by William R. Sellers, MD, director of the cancer program at the Broad Institute, Fang Tian, PhD, director of biological content at ATCC, and Francisca Vazquez, PhD, director of the Cancer Dependency Map (DepMap) at the Broad Institute, the team identified representative classes of resistance mechanisms to osimertinib. They then selected three disease-representative, osimertinib sensitive NSCLC cell lines as the foundation for developing the new isogenic drug-resistant cell models.

ATCC engineered the selected authenticated cell lines with resistance mechanisms using CRISPR-based methods. The six resistance mechanisms included: PIK3CA E545K mutation, KRAS G12D mutation, BRAF V600E mutation, EGFR C797S mutation, CCDC6-RET fusion, and TPM3–NTRK1 fusion.

In addition, scientists at the Broad Institute are generating additional resistant cell lines driven by gene amplification mechanisms using overexpression methods.

These engineered isogenic model systems allow researchers to compare genetically matched cancer cells that differ only by a specific resistance alteration—providing a powerful framework to study how tumors evolve under targeted therapy.

The models will be integrated into the DepMap, a global effort to identify genetic vulnerabilities across hundreds of cancer cell models. The collaboration also contributes to the development of a Response and Resistance Map (ResMap), an emerging framework designed to systematically characterize how cancers respond to therapy and how resistance evolves.

cancer researchers
Engineered isogenic model systems allow researchers to compare genetically matched cancer cells that differ only by a specific resistance alteration—providing a powerful framework to study how tumors evolve under targeted therapy. [Sanjeri/Getty Images]

“Drug resistance remains one of the most significant barriers to durable cancer treatment,” said Kirsty Wienand, PhD, senior research scientist in DepMap at the Broad. “Systematically engineering resistance mechanisms in well-characterized cell models allows us to study how tumors adapt to targeted therapy. Integrating these models into DepMap will help researchers worldwide identify new vulnerabilities and potential therapeutic combinations.”

The collaboration ensures that both the biological models and the associated data will be widely accessible to the scientific community, says the research team. Data will be integrated into the DepMap portal, with links to the corresponding ATCC cell line identifiers. In addition, the engineered cell lines will be distributed globally through ATCC following authentication and quality control.

Systematically engineering clinically relevant resistance mechanisms in lung cancer models, the collaboration establishes a scalable framework for studying how tumors escape targeted therapies, explain the scientists, adding that the resulting models and datasets will help researchers identify new vulnerabilities and therapeutic strategies to overcome drug resistance and improve outcomes for patients with cancer.

By combining advanced cell engineering, functional genomics, and computational biology, the collaboration should provide an important resource for studying drug resistance, cancer vulnerabilities, and precision oncology strategies.

 

ATCC and the Broad Institute will present the research findings at the American Association for Cancer Research® (AACR) Annual Meeting 2026, April 17–22 in San Diego:

Title: Engineering isogenic models harboring resistance mechanisms to the latest-generation EGFR inhibitor in non-small cell lung cancer

Session Category: Experimental and Molecular Therapeutics; Session Title: Drug Resistance 2: Tyrosine Kinase Inhibitors

Date: April 22, 2026, 9:00 AM–12:00 PM, Poster Section 11, Poster Board: 8, Poster Number: 7029

The post Decoding Resistance to Targeted Therapy via New Cancer Models appeared first on GEN – Genetic Engineering and Biotechnology News.

Colossal Biosciences said it cloned red wolves. Is it for real?

If you want to capture something wolflike, it’s best to embark before dawn.

So on a morning this January, with the eastern horizon still pink-hued, I drove with two young scientists into a blanket of fog. Forty miles to the west, the industrial sprawl of Houston spawned a golden glow. Tanner Broussard’s old Toyota Tacoma bumped over the levee-top roads as killdeer, flushed from their rest, flew across the beams of his headlights. 

Broussard peered into the darkness, looking for traps. “I have one over here,” he said, slowing slightly. A master’s student at McNeese State University, he was quiet and contemplative, his bearded face half-hidden under a black ball cap. “Nothing on it,” he said, blandly. The truck rolled on.

Wolves and their relations—dogs, jackals, coyotes, and so on—are classed in the family Canidae, and the canid that dominated this landscape in eastern Texas was once the red wolf. But as soon as white settlers arrived on the continent, Canis rufus found itself under siege. The war on wolves “lasted 200 years,” federal researchers once put it, in a surprisingly evocative report. “The wolf lost.” By 1980, the red wolf was declared extinct in the wild, its population reduced to a small captive breeding population.

Still, for decades afterward, people noted that strange wolflike creatures persisted along the Gulf Coast. Finally, in 2018, scientists confirmed that some local coyotes were more than coyotes: They were taller, long-legged, their coats shaded with hints of cinnamon. These animals contained relict red wolf genes. They became known as the ghost wolves.

Broussard grew up in southwest Louisiana, watching coyotes trot across his parents’ ranch. The thrilling fact that these might have been not just coyotes but something more? That reset a rambling academic career. In 2023, Broussard had recently returned to college after a seven-year pause, and his budding obsession with wolves narrowed his focus. Before he finished his bachelor’s degree, he began to supply field data to a prominent conservation nonprofit.

a wolf pup chews on a terrycloth toy
The American red wolf, Canis rufus, is the most endangered wolf species in the world. This pup is one of four animals said to be clones of this native North American species.
COURTESY OF COLOSSAL BIOSCIENCES

Then, last year, just before he began his master’s studies, he woke to disconcerting news. A startup called Colossal Biosciences claimed to have resuscitated the dire wolf, a large canid that went extinct more than 10,000 years ago. Pundits debated the utility of the project and whether the clones—technically, gray wolves with some genetic tweaks—could really be called dire wolves. But what mattered to Broussard was Colossal’s simultaneous announcement that it had cloned four red wolves.  

“That surprised pretty much everybody in the wolf community,” Broussard said as we toured the wildlife refuge where he’d set his traps. The Association of Zoos and Aquariums runs a program that sustains red wolves through captive breeding; its leadership had no idea a cloning project was underway. Nor did ecologist Joey Hinton, one of Broussard’s advisors, who had trapped the canids Colossal used to source the DNA for its clones. Some of Hinton’s former partners were collaborating with the company, but he didn’t know that clones were on the table.

There was already disagreement among scientists about the entire idea of de-extinction. Now Colossal had made these mystery clones, whose location was kept secret. Even the purpose of the clones was murky to some scientists; just how they might restore red wolf populations was unclear. 

Red wolves had always been a contentious species, hard for scientists to pin down. The red wolf research community was already marked by the inevitable interpersonal tensions of a small and passionate group. Now Colossal’s clones became one more lightning rod. Perhaps the most curious question, though, was whether the company had cloned red wolves at all. 


You can think of the red wolf as the wolf of the East—an apex predator that once roamed the forests and grasslands and marshes everywhere from Texas to Illinois to New York. Smaller than a gray wolf (though a good bit larger than a coyote), this was a sleek beast, with, according to one old field guide, a “cunning fox-like appearance”: long body, long legs; clearly built to run across long distances. Its coat was smooth and flat and came in many colors: a reddish tone that comes out in the right light, yes, but also, despite the name, white and gray and, in certain regions and populations, an ominous all black.

We know these details thanks to a few notes from early naturalists. As writer Andrew Moore writes in his new book, The Beasts of the East, by the time a mammalogist decided to class these eastern wolves as a standalone species in the 1930s, the red wolf had been extirpated from the East Coast and was rapidly dwindling across its range. Working with remnant skulls and other specimens, the mammalogist chose the name red wolf—which was later enshrined with the Latinate Canis rufus—because that’s what these wolves were called in the last place they survived. 

The looming extinction of the red wolf turned out to be a good thing for coyotes. Canis latrans is a distant relative of wolves that split away from a common ancestor thousands of years ago and might be considered, as one canid biologist put it to me, the “wolf of the Anthropocene.” Their smaller size means they need less food and can survive in smaller and more fragmented territory, the kind that modern humans tend to build. 

The last red wolves, which lived in Louisiana and Texas, decided a strange and smaller mate was preferable to no mate at all.

Red wolves had kept coyotes out of eastern America, outcompeting them for prey. Now, as the wolves declined, the coyotes began to slip in. The last red wolves, which lived in Louisiana and Texas, decided a strange and smaller mate was preferable to no mate at all. Soon the territory became a genetic jumble, home to both wolves and coyotes and hybrids that, after several generations of intermixing, came in every shade between. Scientists call such a population a “hybrid swarm,” and it poses a genetic threat to the declining species: As more coyotes poured east, and as all the canids kept interbreeding, there would be nothing that was “purely” wolf. 

""
Ron Wooten surveys a location on the edge of Galveston Island State Park in Texas. In 2016, Wooten’s photographs of oversized local coyotes got the attention of Joey Hinton, then a postdoctoral researcher at the University of Georgia.
TRISTAN SPINSKI

For years, no one seemed to notice. Perhaps trappers in the region mistook the new hybrids for wolves—or were happy to take the higher bounty that a wolf pelt earned. Finally, though, by the 1960s, as the concept of endangered species first emerged, biologists began to worry for the disappearing wolf. 

The best solution they could come up with was a program of mass extermination. Over several years, trappers rounded up hundreds of canids in Texas and Louisiana. Those deemed true red wolves (on the basis of their howls and skull shape) were whisked away to breed in captivity. Most of the rest were euthanized. In 1980, the red wolf was declared extinct in the wild. To put it plainly: The red wolf was wiped out intentionally, in a roundabout effort to keep it alive.

Just 14 individuals survived this gauntlet; today’s wolves descend from 12 of those. They became the ark, the source material for the few hundred red wolves that live today. There are about 280 in the “Species Survival Plan” population, living in captivity, and another 30 or so that roam a federal refuge in coastal North Carolina, and that the government deems “nonessential” and “experimental.” According to the US Fish and Wildlife Service, to be classified as a representative of the protected entity known as Canis rufus, an animal must trace at least 87.5% of its lineage to the 12 founders. 

The scientist who led this trapping-and-breeding program understood that the federal government would be narrowing the red wolf’s gene pool precipitously—so much so that the result could be an entirely new species. None of those notably black wolves persisted in the new population, for example. But what other choice existed? A new kind of wolf, free of the taint of the invading coyote, seemed better than no wolf at all.


After I learned about Colossal’s clones, I decided to travel to eastern Texas. The clones were hidden away on an unnamed refuge, but on this coastline, I might be able to at least see the animals that provided their genetic material. I arrived in the small town of Winnie on a balmy afternoon in January and met up with Broussard and another graduate student, Patrick Cunningham, at a Tex-Mex joint to discuss the challenges of studying red wolves.

“We don’t have a good reference genome,” Cunningham said. We can collect DNA from the descendants of the 12 founders, but not from the countless wolves that had been killed. It’s difficult to extract usable DNA from old samples. So our picture of what the species used to look like is limited. 

Studies of the genes we do have, meanwhile, have proved controversial. When a Princeton geneticist named Bridgett vonHoldt dug into the genome of the Species Survival Plan population, she found little about their DNA that could set them apart from other wolflike American canids. In 2016, in a paper in Science Advances, vonHoldt and her coauthors wondered if there ever really was a separate southern wolf species. Perhaps the 12 founders were just coyotes injected with some smaller portion of wolf.

It’s long been clear that North America’s soup of Canis genes is something less like a family tree and more like a river—one that’s broken by islands and sandbars into many braided channels that split and merge and re-split.

Her paper called for complex new interpretations of the Endangered Species Act. We should, she wrote, focus less on species and more on the function a group of animals performs. The red wolves deserved protection, then, as creatures that filled the same role as truly endangered wolves and carried some of their genetics. Nonetheless, for Canis rufus, the timing of the paper was bad news.

The red wolves roaming that federal reserve in North Carolina are supposed to be a first step toward the species’ return to the wild. But some locals never liked the idea of living alongside wolves. By 2016, state officials had turned against the recovery program and were requesting its termination. The wild population, which had included as many as 120 a few years earlier, was falling. But the US Fish and Wildlife Service had paused further releases of wolves. Now a group of scientists, led by vonHoldt, was saying that the red wolf showed “a lack of unique ancestry.” Why spend money, some people wondered, on a species that does not exist? 

Part of the problem was that the concept of a “species” is less sturdy than your high school biology teacher might have led you to believe. The most familiar definition is that a species consists of animals that can produce fertile offspring. But that’s a rule various species of canids violate all the time; it’s long been clear that North America’s soup of Canis genes is something less like a family tree and more like a river—one that’s broken by islands and sandbars into many braided channels that split and merge and re-split.

VonHoldt suggested that the modern red wolf is a channel in that river, part wolf and part coyote, that appeared surprisingly recently. But a year after her study came out, other researchers claimed that her data, if interpreted differently, could suggest that the red wolf braid had emerged tens of thousands of years ago, meaning this was a species that had long been on its own evolutionary journey. 

These nuances were confusing for the policymakers who oversaw actual, living animals. “Congress was just like, ‘What is going on?’” Cunningham said. “‘Why is there not just a simple explanation for what this thing is?’”

Given the policy implications, the National Academies of Science, Engineering, and Medicine tasked a panel of scientists with finding that simple answer. Their report, published in 2019, declared that the red wolf is, by virtue of its appearance and seemingly long-standing isolated population, a species. As their study got underway, though, a new question was arising: What to make of the strange canids on the Gulf Coast, those today called the ghost wolves?


The path to that name began in 2008, when a photographer from Galveston Island, Texas, grew obsessed with the oversized local coyotes. He began to take photos of the packs, which he distributed to scientists, seeking answers: What were they? By 2016, the photos had reached Joey Hinton, then a postdoctoral researcher at the University of Georgia.

Hinton had spent more than a decade trapping wolves and coyotes in North Carolina, and his work has always focused on live animals, especially visual ways to distinguish red wolves and coyotes. So he was a good choice for helping the photographer, Ron Wooten, figure out the status of the canids. In his freezer Wooten also had tissue samples he’d collected from road-killed coyotes. These could be used by a geneticist to give a fuller picture of the canids’ ancestry. So vonHoldt was brought in too. The result was a 2018 paper, with Hinton as a coauthor, that identified the Galveston Island canids as at least part red wolf.

These canids were not, to be clear, actual red wolves; no canid on the Gulf Coast is descended from the government’s 12 canonical founders, so under current policy, none can be officially classified as a wolf. Subsequent studies have found that, on average, the ancestry of the region’s canids is less than half red wolf, and often far less. In scientific terms, the red wolf had introgressed into the Gulf Coast population—its genes had leaked across the species boundary and lodged themselves in a different population.

Hinton, vonHoldt, and their coauthors also noted the presence of what they called “ghost alleles”—DNA sequences unknown in any other named species. The Occam’s razor assumption was that, in these already wolfy coyotes, these sequences likely represented Canis rufus genetics that had not been captured in the sweep of the marsh that yielded the Species Survival Plan population. Since so much of the red wolf gene pool had been lost, these genes seemed to be a potential resource for the species—a way to expand its diversity. When the New York Times covered this discovery a few years later, the headline popularized the “ghost wolf” moniker that has proved so indelible. 

As it happened, a separate team, focused on canids in and around federally protected marsh in Louisiana, published a similar paper in 2018, at nearly the same time. The twin discoveries raised new questions—What should we make of these creatures, the latest branch in the canid river? What do they mean for the wolves in North Carolina?—and helped researchers secure new funding.

In 2020, vonHoldt and Kristin Brzeski, a former postdoc under vonHoldt and now a professor at Michigan Technological University, launched what they called the Gulf Coast Canine Project. Brzeski, who led the field work, hired Hinton to do much of the canid trapping and sample collection. In 2022, vonHoldt, Hinton, and Brzeski were all coauthors of another paper that identified even more red-wolf-descended canids in Louisiana and noted a positive correlation between red wolf ancestry and body mass—the more red wolf genes, the bigger the animal. The paper also suggested that given this newly discovered reservoir of red wolf DNA, “genomic technologies” could prove useful in the long-term survival of the species.

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Bridgett vonHoldt (left) and Kristin Brzeski (center) visit a location where canids have been spotted with an animal control worker.
TRISTAN SPINSKI

VonHoldt and Brzeski eventually conceived of an ambitious project. They hoped that by carefully matching the most wolf-­descended canids and breeding them together, over three generations they’d increase the proportion of red wolf genes—de-introgression. “I’m expecting, based on these pairings of animals, that I can stitch together the puzzle pieces,” vonHoldt told me recently. “We are very likely to get puppies each generation that are higher and higher red wolf content”—enough wolf content, she hopes, to eventually win her permission to breed the resulting animals with the Species Survival Plan population of red wolves. They’d essentially be adding a new founder to the limited lineage.

Hinton told me he felt he’d been kept in the dark about the de-introgression idea. He was also worried, he says, to learn that Colossal Biosciences hovered in the background. (In a draft proposal for the project, vonHoldt indicated that Colossal would be in charge of “live capture.”) Hinton says he was not comfortable collecting materials for a for-profit company that has to keep its shareholders happy. 

Hinton says he reached out to state and federal officials and found they knew little about the project. (The US Fish and Wildlife Service declined to make anyone available for an interview for this story, and the Louisiana Department of Wildlife and Fisheries did not reply to requests for comment.) He knew the group’s next phone call would be difficult, and indeed it was. He wound up speaking one-on-one with vonHoldt for at least half an hour.

“We didn’t reach an agreement,” he says. After the call, he sent her a text: He was exiting the project. He believes that had Colossal not been involved, they’d all still be working as a team. Both vonHoldt and Brzeski declined to comment on what felt to them like a matter of interpersonal relationships rather than a scientific dispute. “There were challenges over time, and the tone and manner of the interactions became increasingly difficult to navigate productively,” Brzeski said in an email. 


Colossal was cofounded in 2021 by George Church, an eminent Harvard geneticist who, thanks to investors, could finally embark on a long-discussed dream. He wanted to make de-extinction a reality—using CRISPR gene-editing technology to, say, turn a modern elephant into something like the extinct woolly mammoth. The concept has drawn skepticism from the beginning—at best it would only be possible to make something like a woolly mammoth. Was there any point to that? Some scientists note that genes alone do not teach an animal how to exist in the world; indeed, since social structures affect how genes are expressed, an animal without parents may not effectively fill its ecological niche.

Less reproachable, though, was Colossal’s interest in partnering with scientists who, like vonHoldt and Brzeski, focus on extant species that are endangered. This gave more heft to Colossal’s gee-whiz de-extinction projects: They would, along the way, supply technology that could save our natural world.

For red wolves, such technologies could offer a quick way to expand the limited gene pool. Through genetic engineering, Colossal could take clones of the Gulf Coast canids and tune up the wolf, tune down the coyote. It would be a high-tech shortcut past vonHoldt and Brzeski’s careful breeding program. “You can do the same thing much more precisely, much more quickly, much more efficiently, in vitro,” says Matt James, Colossal’s chief animal officer and the executive director of the Colossal Foundation, the company’s nonprofit arm. VonHoldt notes that the old-fashioned approach, with breeding, means she has to take a few individual canids out of the wild, into captivity—never ideal but, in her view, a worthwhile price for progress. The advantage of cloning, which Colossal has managed to do with blood samples alone, is that the wild canid populations can be kept intact. 

VonHoldt has always been an advocate for wolves. Indeed, when she hypothesized that the red wolf had hybrid origins, in 2016, she’d framed it as an argument for protecting the gray wolf, which the federal government was considering removing from the Endangered Species List. (In short: If all wolves were one wolf, then it was undeniable that the species’ range had contracted precipitously.) But she’d grown frustrated with the federal government’s efforts to restore the red wolf, which after half a century had seen few meaningful successes, she says. 

VonHoldt joined Colossal’s scientific advisory board in 2023. “I love the bold, the shock and awe,” she told me, explaining her decision. She saw the fact that Colossal sparked controversy as an asset, given the problems she sees in conservation: “Get something out there. Start pushing buttons and start forcing these conversations,” she says. The red wolf was akin to a terminal patient who was ready to accept any and all therapies, however experimental. Why not embrace biotech? 

She also notes that the federal budget for endangered species conservation is incredibly limited. Rely only on that money and “we can kiss our world goodbye,” she said in an e-mail. The $100 million raised by the Colossal Foundation is essential, then, she says. As for the samples the team had collected on the Gulf Coast, she says, limited freezer space is often devoted to animals that are officially categorized as threatened or endangered, which the Gulf Coast canids are not. Colossal could take the samples, and the team passed them along to the company.

Dr. Joey Hinton
Ecologist Joey Hinton trapped the canids that Colossal Biosciences used to source the DNA for its clones. He dismisses the clones as a way for the company to earn headlines and attract funding.
RICH SAAL

It was Hinton—a source for a former story—who first alerted me to Colossal’s work on red wolves; he described vonHoldt and Brzeski’s de-introgression project, which won federal funding in late 2024, as nefarious-sounding work to “disappear” canids off the Gulf Coast. But he did not have all the details of the project, which had changed after he left the team. He suggested they’d be “just throwing animals together,” whereas vonHoldt described a careful program of observing the canids in the wild so she could determine which acted most wolflike, findings she’d cross-­reference with their genetic data.

 Colossal did not wind up participating in the de-­introgression project. But the company is doing work on the red wolf that ­vonHoldt views as complementary: Its scientists are assembling a “pangenome” of North American canids by studying samples pulled from museums, universities, zoos, and other institutions. This data set is expected to clarify both what genetic sequences are shared across the entire canid family and what snippets differ in certain populations. The hope is that this will provide a clearer picture of the red wolf in its early days, before the coyotes arrived and the gene pool narrowed. That might shift what Colossal’s James calls the government’s arbitrary definition of the red wolf, to encompass more of the species’ full former diversity. 

The pangenome, then, might allow vonHoldt’s de-­introgressed canids, descended from the Gulf coast canids, to qualify as actual red wolves. Indeed, James suggested to me that more information about historic red wolves might force the government to take a new look at the Gulf Coast canids; some individuals might have high enough red wolf ancestry to be classified as red wolves. (“That has management implications that terrify state and federal government,” he added.)

hair in Zip-Loc bags on a metal tray
Blood and tissue samples collected by the Galveston Island Humane Society from canid roadkill will be shipped to Princeton University for DNA analysis.
TRISTAN SPINSKI

The purpose of vonHoldt’s de-introgression project is to bring back certain lost red wolf genes—to create a whole new wolf lineage. But she has also pushed against the idea of “genetic purity,” which she thinks limits what we protect with conservation laws; she told me emphasizing it reminds her of the human history of eugenics and “makes every part of my soul hurt.” She cares less about what species are out there, in the landscape, than what ecological function the animals play, and she sees coyotes and red wolves as closely related animals that may have a role to play in one another’s future survival.


As for Colossal’s clones, even vonHoldt seems to describe them as something less than a conservation breakthrough. They are a “proof of principle that we, collectively, as a scientific community, know how to do it,” she told me. If an urgent need arises to clone red wolves, the groundwork has been laid. 

Hinton, meanwhile, is one of several scientists I spoke with who were skeptical Colossal was doing good science, given that so much is conducted behind closed doors. He implied that the clones were nothing but an empty showpiece, a way to earn headlines and attract funders. “The work is anything but symbolic,” James responded via e-mail. “It expands the genetic toolkit available for critically endangered species, demonstrates scalable approaches to biodiversity restoration, and contributes directly to preserving imperiled lineages.” He noted that Colossal had intentionally decided to avoid the “snail’s pace” of the peer review process and suggested that the skepticism from scientists may actually be a “panicked response to being outpaced.”

Until some evidence confirms that the Gulf Coast canids—the source material for the clones—are red wolves, they can’t legally be classified as such for federal conservation purposes. Nonetheless, Colossal’s press release claimed that the company had “birthed two litters of cloned red wolves, the most critically endangered wolf in the world.” On the same day that press release dropped, Colossal’s CEO and cofounder, Ben Lamm, appeared on The Joe Rogan Experience and claimed that he had offered to create hundreds of red wolves for the federal government to use in recovery—for free! He was miffed when the government, under the Biden administration, replied that it wanted to spend several years and many millions of dollars to study the potential for cloning before it would take any action. (The company has gotten more traction with the Trump administration, Lamm said.)

When I first spoke to James at Colossal, he said that he was “cognizant” of the concerns over the names and labels and that the company’s own materials described the clones as “red ‘ghost’ wolves.” He suggested that if anyone assumed the clones were actual red wolves, that was because journalists had failed to grasp the nuances of the science. But this phrase appears so late in a long document that it was cut off in some versions. Later, over email, James indicated that further analysis had convinced him that what the company had created were red wolves, and that anyone who disagreed either could not grasp the science or is “so ideologically opposed to Colossal’s conservation revolution that they are willing to compromise their scientific integrity.”

VonHoldt has had her own issues with the company’s communications; she told me it was “stressful” when Lamm described the clones as red wolves—which, she notes, “federally, they’re not.” But she values the company’s work, she says, and “the thing that I value the most is shaking things up.” People are paying attention to red wolves. If it’s hard to decide what to call the animals on the Gulf Coast—where some heavily wolfy animals live alongside others that are more coyote—that’s just proof that our concept of a “species” does not capture the complex realities on the ground. 


In 2025, the same year as Colossal’s wolf announcement, Hinton launched the Texas-Louisiana Canid Project. He’s working in partnership with Broussard, the master’s student at McNeese, in slightly different territory from vonHoldt and Brzeski—and focusing more on the animals’ appearance and behavior than their genes. The Gulf Coast canids are stable and faring better than the North Carolina red wolves, and his hope is that if we learn why they’ve been successful for so many years, we might be able to help the official red wolf population, which is only just limping along. 

a wolf crosses a road outside of the city
Galveston locals hope that the presence of these remarkable creatures—red wolves or not—might rein in the rapid development of the island’s last stands of green.
TRISTAN SPINSKI

I had planned to join Hinton in the field, but by the time I was able to visit, he’d had to go home to his family. So I joined Broussard on his last days trapping in Texas that season. Before I’d left for Winnie, I’d told my friends I’d be out chasing the last surviving red wolves. But there, on the Gulf Coast, I came to understand that this was just as much a story about coyotes.

That’s what Broussard and Cunningham both called the creatures. Hinton does too; he considers the animals to be a specific “ecotype” of coyote, featuring an injection of wolf DNA that has helped them adapt to the local marshes. 

At vonHoldt’s behest, I drove an hour down the coast to Galveston Island, where she and Brzeski began working with the island’s animal control department; when locals find a coyote, the animal is captured so its blood can be collected and a GPS collar fitted on its neck. A small group of locals who support the project have come to call themselves the “ghost wolf team.” They hoped that the presence of these remarkable creatures might rein in the rapid development of the island’s last stands of green. Still, the people I spoke to in Galveston conceded that the animals were, if special, nonetheless a form of coyote. 

VonHoldt describes Galveston Island as a potential model for what conservation could look like in the future. Top-down recovery hasn’t been working, but helping more places fall in love with their local animals might. And for that to happen, we need to stop obsessing over whether or not something is a “pure” wolf. What matters, she argues, is that an animal is doing what a larger predator does in an ecosystem. She embraces the “ghost wolf” name because, more than “Gulf Coast canid,” it makes clear that there’s something special on the coast—something worth protecting. 

Her vision is enticing: Focus on function over purity. Let evolution proceed. Stop protecting the wolf of the past and consider the wolf of the future. Such rapid genetic exchange may be necessary to help predators adapt to a hotter, increasingly shattered world, she says. 

If we throw out the concept of “endangered species,” will we really protect “endangered functions” instead?

Then again, we already know what’s adapted to the world we’re building: coyotes. The argument against genetic purity can sound like giving up on wolves entirely, with the possible exception of whatever specimens we produce in cloning facilities. And there is the matter of politics: If we throw out the concept of “endangered species,” will we really protect “endangered functions” instead? Under an administration already rolling back environmental protections, the likeliest outcome may be protecting nothing at all.

I tried in Galveston, too, to see the coyotes. Ron Wooten, the local resident who helped alert scientists to this population, dropped some pins on a map, pointing me toward several likely spots. That evening, after the sun set, I chose a quiet road that passed through marshes until it reached the island’s eastern beach. It was mating season, Wooten had noted. The animals should be on the move, he said; look to the bushes. As I drove up and down the road, my headlights revealed only empty darkness. No coyote. No wolf. Fitting, perhaps—isn’t absence the essence of a ghost? But whether this was a good omen was less clear. As individuals, these animals do best by avoiding us humans. As a group, their survival—like the survival of the red wolves—depends on our knowing that they are here, and were here, and deciding that is reason enough to care.

In Winnie the next morning, I went out one last time with Broussard, and we struck out again. With no coyotes in his traps and the new semester looming, he decided to take down his game cameras. Back at the hotel, I caught at least an image of what I’d been chasing: In black and white, the animals were appropriately silver, spectral, dashing across the midnight fields. In one clip, a canid paused and howled. “That’s super cool,” Broussard said quietly, as an echoing, interweaving chorus responded from somewhere deeper in the marsh. 

Boyce Upholt is a journalist based in New Orleans and founding editor of Southlands, a magazine about Southern nature. 

Opinion: Politicians are using low teen birth rates to further restrict access to birth control, abortion

Recently, the Centers for Disease Control and Prevention published its most recent estimates of live births in the U.S. It showed that birth rates continue to decline nationwide, and teen birth rates specifically are at record lows. These findings have drawn widespread media attention and will certainly fuel the pronatalist movement’s concern that fewer people are getting married and having children. In fact, a senior medical analyst for Fox News explicitly described low teen birth rates as “the problem” driving overall fertility declines. He is not alone in this belief.  

As a public health behavioral scientist who has spent my career researching adolescent access to sexual and reproductive health care, I felt a startling sense of whiplash upon hearing these panicked reactions. When I was at the CDC in the 2010s, during the “teen pregnancy prevention” era, these same data reports documenting declining teen birth rates were cause for celebration.

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LiveWell mBC Pilot RCT

Conditions: Survivorship

Interventions: Behavioral: LiveWell mBC: A Group-Based Adapted Dialectical Behavioral Therapy Skills Training Program

Sponsors: Medical University of South Carolina; American Cancer Society, Inc.

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