Cholera, caused by the bacterium Vibrio cholerae, remains a major global health threat. Like most bacteria, Vibrio cholerae lives under constant attack from viruses. To survive, bacteria equip themselves with antiviral immune systems. Previous work has shown that V. cholerae carries a large genetic element called a sedentary chromosomal integron (SCI). This structure contains hundreds of small mobile DNA units known as “gene cassettes” arranged in a long array, like a chain of pearls. A new study by researchers at the School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), has now shown that V. cholerae can efficiently acquire new SCI gene cassettes from extracellular DNA released by other V. cholerae strains, and non-cholera vibrio species, potentially adding to their own defense arsenals.
Research lead Melanie Blokesch, PhD, and colleagues reported on their findings in Science, in a paper titled “Competence-mediated DNA uptake diversifies Vibrio cholerae sedentary chromosomal integrons,” in which they concluded “Given the widespread presence of SCIs and the conservation of natural competence across the genus, we propose that SCIs function as genus-wide reservoirs of exchangeable protective genes.”
Bacteria often survive viral attack and environmental stress by sharing genes that enhance their defenses, the authors wrote. A “defining genomic feature” of V. cholerae is its sedentary chromosomal integron (SCI), a genetic element containing hundreds of mostly promoterless gene cassettes. While the function of many cassettes remains unknown, some do encode antiviral immune systems. “Although most cassettes encode proteins of unknown function, ~10% encode phage defense systems, suggesting that SCIs as well as mobile integrons function as reservoirs, or “biobanks,” of defense genes,” the authors continued.
However, most of these genes are located far from the start of the array and remain silent. Prevailing models proposed that cassettes could be internally reshuffled to activate them, yet no such rearrangements have been observed in the pandemic lineage of V. cholerae for decades. “Cassettes are thought to reshuffle under stress to the favorable first array position, yet the SCI in pandemic V. cholerae has remained static for more than 60 years.”
This raises a key question: if internal reshuffling is rare, how are cassette-encoded immune systems activated, and how do new cassettes enter the array at all? To address this question, a team led by Blokesch at the Laboratory of Molecular Microbiology at EPFL investigated whether the SCI might capture gene cassettes from genetic material entering the cell from the outside. “We asked whether SCI cassettes move horizontally rather than by intracellular reshuffling.”
A key feature of this process is natural competence, the ability of bacteria to take up free DNA from their surroundings. V. cholerae becomes naturally competent when it grows on chitinous surfaces, a polymer found in the shells of crustaceans that is abundant in aquatic environments.
In the laboratory, the team mimicked these conditions by growing bacteria on chitin and supplying DNA from different Vibrio cholerae strains or from other Vibrio species. They then tracked whether newly acquired gene cassettes were inserted into the first position of the SCI array.
Through their studies the team confirmed that that V. cholerae can acquire new SCI gene cassettes from extracellular DNA. Collective experimental results, the authors stated, “We show that SCI cassettes are efficiently acquired by naturally competent V. cholerae and inserted at the first SCI array position in an integrase-dependent manner. This process incorporates cassettes not only from other V. cholerae strains but also from diverse Vibrio species.”
In aquatic habitats, DNA is released when bacterial cells are killed by viruses, antimicrobial compounds, or bacterial weapons. Nearby competent bacteria can take up this DNA and incorporate selected fragments into their own SCI. “A loose comparison would be the following,” said Blokesch. “Imagine your grandmother passes away and, as a farewell gift, hands over the immunity she built up against the Spanish flu a century ago, immediately protecting you from that same virus. Wouldn’t that be amazing? This is essentially what we show that V. cholerae can do.”
The team also showed that cassettes inserted in this position are functional. Several defense systems provided protection against viruses that infect Vibrio species, known as vibriophages. They stated, “In this study, we show that SCI diversification efficiently occurs by horizontal transfer linked to the genus’s aquatic lifestyle: DNA released from lysed cells is taken up by naturally competent vibrios and integrated into the first position of the SCI array, the primary site of strong expression, where it confers resistance to phage and potentially other threat,” the wrote in summary. “Together, these results demonstrate that SCI cassettes can cross species boundaries, supporting a model in which SCIs may function as genus-wide reservoirs of exchangeable genes, including defense genes, that confer selective advantages under certain conditions.”
An important exception emerged. In the pandemic 7PET lineage of V. cholerae, the SCI appears largely static. “The SCI of 7PET V. cholerae is large but remarkably stable,” the authors noted. They propose that this reflects adaptation to a human-associated niche. “We propose that this reflects adaptation to a human-associated niche, where chitin is less abundant and competence induction—requiring growth on chitin to high cell density plus relief from catabolite repression is unlikely to occur,” they suggested. “As a result, SCI-mediated diversification may be largely inactive in pandemic strains.”
However, if pandemic strains were to encounter environmental conditions that enable SCI cassette acquisition, they could expand their antiviral defenses. Blokesch commented. “This possibility matters because vibriophage-based approaches are currently being explored to prevent cholera in endemic regions, and such evolutionary flexibility could ultimately affect how effective these strategies remain.”
In their paper the team concluded that since onset of the seventh pandemic, “… acquisition of novel and diverse, large defense-related genomic regions by 7PET strains appears to have been relatively limited. Consequently, reduced SCI-mediated diversification may lower the capacity of this lineage to rapidly evolve new defenses—an important consideration for ongoing efforts to deploy phage-based prophylaxis against cholera in endemic settings such as Bangladesh.”
This week, Seer, a developer of proteomics technology, said that scientists involved in the PRECISE-SG100K initiative will use the company’s Proteograph® product suite to profile the plasma proteome of about 10,000 participants. The data from this workflow will be combined with information from the same participants that was generated using Thermo Fisher Scientific’s Olink® Reveal, a next-generation sequencing-based proteomics solution, and its Orbitrap Astralmass spectrometers.
PRECISE-SG100K is the second phase of a broader initiative in Singapore that aims to support various research studies that advance scientists’ understanding of health and diseases. Touted as a landmark population study of approximately 100,000 Singaporean residents, PRECISE-SG100K is designed to integrate genomic, proteomic, lifestyle, imaging, and other health data from a multi-ancestry Asian population. By combining data from Seer’s Proteograph platform alongside information from other technologies that are being used for the project, the scientists aim to develop what they believe will be one of the most comprehensive multiomic datasets available to date.
“PRECISE-SG100K is one of the most ambitious and carefully designed multiomic health initiatives in the world,” said Omid Farokhzad, MD, PhD, chair and CEO of Seer. And that fits with Seer’s vision for Proteograph, which was that “deep, unbiased proteomics becomes the mainstay for population-scale multiomic studies.”
Seer already has an existing relationship with Thermo Fisher dating back several years. In 2024, the companies announced a co-marketing and sales agreement that allowed Thermo to jointly promote Proteograph alongside Orbitrap Astral mass spectrometers to provide customers of the Orbitral Astral with an integrated solution for unbiased proteomic analysis. The combined solutions have since been used in a number of large population studies providing high-throughput, deep proteome coverage.
“A key goal of PRECISE-SG100K is to create a deeply characterized, multi-ancestry resource that can reveal how genetics, environment, and lifestyle shape disease risk and treatment response,” said John Chambers, PhD, chief scientific officer of PRECISE and lead principal investigator of the PRECISE-SG100K study. “By adding deep, unbiased plasma proteomics enabled by Seer and Thermo Fisher, we can more directly link genomic variation to protein networks and health outcomes, uncovering insights critical to ensuring precision medicine reflects the diversity of Asian populations.”
Ultimately, the data generated from population projects like this are expected to support biomarker discovery in key disease areas including cardiometabolic, ophthalmic, and neurologic disorders. They could also inform the development of predictive models for assessing disease risk and response as well as efforts to validate and prioritize biomarkers identified through affinity-based platforms.
Background: Blended digital mental health interventions combining technology with human support are more effective than stand-alone treatments. However, limited research has examined how to train and supervise personnel delivering human support components. The Kuamsha app, a gamified digital intervention for adolescent depression based on behavioral activation, was designed to be paired with low-intensity telephone-based peer support. A structured training and supervision program for peer supporters was codeveloped through workshops with mental health professionals and youth with lived experience of mental health challenges in South Africa and Uganda. To the best of our knowledge, this is the first study to evaluate a structured peer mentor model within a digital mental health intervention in low- and middle-income countries. Objective: This study assessed the feasibility, acceptability, and fidelity of a training and supervision program for peer supporters delivering a digital mental health intervention in South Africa and Uganda. Methods: We conducted a mixed methods evaluation of the peer mentor program. Quantitative metrics assessed the feasibility of recruitment, retention, and attendance among peer mentors (n=13, South Africa; n=4, Uganda), as well as training acceptability. Fidelity, adherence, and competence were scored at the session level and converted to percentages of the maximum possible score. Linear mixed-effects regression models with a random intercept for provider and site estimated adjusted marginal means (95% CI). In-depth interviews and focus group discussions explored program acceptability and implementation factors. Results: The peer mentor training and supervision program was feasible and acceptable in both settings, with high recruitment (South Africa: n=13/19, 68%; Uganda: 4/4, 100%), retention (South Africa: 9/13, 69%; Uganda: 4/4, 100%), and training attendance rates (89%‐92% in South Africa and 100% in Uganda), alongside qualitative reports of high satisfaction. All peer mentors met a minimum posttraining competency threshold (≥50%), with median competency scores of 70.7% (IQR 45.8%‐78.2%) in South Africa and 75.4% (IQR 73.8%‐77.3%) in Uganda. Independent ratings of recorded calls indicated high overall fidelity in South Africa (84.7%, 95% CI 80.3%‐89.0%) and Uganda (87.7%, 95% CI 83.4%‐92.1%). Adherence was higher in Uganda than South Africa (adjusted mean difference [AMD] 13.30 percentage points, 95% CI 8.99‐17.61; <.001), as was competence (AMD 4.88 percentage points, 95% CI 1.23‐8.53; =.009). The AMD in overall fidelity (3.06 percentage points, 95% CI −0.98 to 7.10) was not statistically significant (=.14). The qualitative findings emphasized the value of ongoing supervision and capacity development, interactive training approaches, and blended delivery models. Conclusions: Locally adapted training and supervision models can strengthen peer mentor capabilities to support digital interventions. Adequate supervisory capacity and incentive structures are critical to sustain engagement, retention, and fidelity. In settings with frequent network disruptions, periodic in-person contact between peer mentors and supervisors may enhance fidelity. Future research should examine how peer mentor fidelity influences user engagement and mental health outcomes. Trial Registration: Pan African Clinical Trials Registry PACTR202206574814636; https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=23792 International Registered Report Identifier (IRRID): RR2-10.1136/bmjopen-2022-065977
Dr. Edna Foa served for decades as a professor of clinical psychology in psychiatry at the University of Pennsylvania, where she also directed the Center for the Treatment and Study of Anxiety (CTSA), the internationally renowned program she founded in 1979. Through the CTSA, Edna created not only a hub for groundbreaking research, but also a training ground that would shape the future of evidence-based treatment for anxiety, obsessive compulsive disorder (OCD), and post-traumatic stress disorder (PTSD).
At a time when OCD was poorly understood and often ineffectively treated, Edna helped establish and rigorously validate exposure and response prevention (ERP) as a gold-standard intervention. Building on the early behavioral work of pioneers before her, she brought a level of empirical precision, clinical sophistication, and dissemination that transformed ERP from a promising approach into a cornerstone of modern treatment. In doing so, she fundamentally changed what recovery could look like for millions of people living with OCD.
Her influence extended well beyond OCD. Dr. Foa was also a central figure in the development of cognitive-behavioral models and treatments for PTSD, including prolonged exposure therapy, which has become one of the most widely used and effective interventions for trauma-related disorders. Across both domains, her work exemplified a rare integration of theory, research, and clinical application—always grounded in a singular goal: to reduce suffering and restore lives.
Her connection to the International OCD Foundation (IOCDF) was a natural extension of her commitment to bridging science and real-world impact. Edna was deeply engaged with the IOCDF community over many years, contributing to its mission of improving access to effective treatment and advancing understanding of OCD. The Foundation awarded her with the Outstanding Career Achievement Award in 2011. She was a frequent presence at conferences, where she not only shared her research but also helped elevate the standards of clinical care through teaching, mentorship, and collaboration.
The IOCDF’s growth into a global leader in OCD advocacy, education, and training reflects, in many ways, the scientific foundation that Edna helped build. Her work made it possible for organizations like the IOCDF to promote treatments that are not only evidence-based, but truly life-changing. And through her direct involvement, she helped ensure that the connection between research and practice remained strong, dynamic, and accessible.
Edna Foa showed us what it means to dedicate a life to advancing knowledge in the service of humanity. She illuminated a path forward for so many, and her influence will continue to guide the field for generations to come.
Below are several tributes to Dr. Foa from IOCDF community members.
From Jonathan Grayson, PhD
My mentor, Tom Borkovec, used to talk about our psychological lineage; that in 1979, you only had to go back a few generations of your “forefathers” to reach the founders of American psychology. In this respect, Tom is my psychology father – he taught me to discipline my thinking – he encouraged wild flights of speculation, but to always temper it in print with what could be researched and proved. With this in mind, Edna is my psychology mother. As I noted elsewhere, for all of us who work with OCD, we are her children, grandchildren and so on.
I first met Edna in 1979 at Joseph Wolpe’s Behavior Therapy Unit at Temple University. She hired me as an adjunct research assistant professor. This was in the ancient days at the height of the first wave. There was no cognitive behavioral therapy. ABCT was AABT, American Association of Behavior Therapy. The disorder we were studying was OC, the DSM labeling it obsessive compulsive disorder doesn’t yet exist. Edna was on the first of her landmark OC grants.
She was the flashpoint for all that we do with OCD. Don’t get me wrong, she didn’t invent ERP, but her work was/is the basis of all OCD treatment today. In the same way that cognitive therapy techniques existed before Aaron Beck, but his work was the flashpoint of that second wave; and the techniques of ACT pre-exist Stephen Hayes, but his work and thinking were the flashpoint of the third wave. There was no OC Foundation.
I joined Edna and Gail Steketee and to work with Edna was always a collaboration. So many hours of discussing, designing and analyzing research. Writing papers together often until midnight and beyond. You may have heard that Edna was demanding. She was, but that had nothing to do with the hours we worked. The same clinical skills she used with patients, she used in choosing those who worked with her. We were all driven. There are those who found her direct delivery difficult, but it wasn’t anger or belittling, it wasn’t intimidating (okay, maybe a little), she was simply direct without sugar coating. The truth about Edna was that she was caring and very generous.
As I said, our research was a collaboration and the order of authors on publications reflected our contributions. If you had a research idea that was tangential to her main projects, she would support you. When I told her I thought we should have support groups to help sufferers maintain their gains, I was given a free hand to develop and run GOAL as I saw fit. When my son was nine months old and I told Edna that I was going to change my work hours to: one and a half daytime hours and the rest of my hours after 4 pm, she accepted this. She didn’t have to admonish me or warn me to do my job, Edna knew the kind of people she had chosen. She wanted the people who worked with her to grow. When it came time for me to move on, she was like any parent, sorry for me to go, but happy for me to pursue my life. She was like that with all of us. So many of those who have shaped the OCD world worked with Edna. While I was there, Michael Kozak joined the team and later Edna and Michael published their ground breaking paper on emotional processing. Alec Pollard, Charly Mansueto and Rich McNally also passed through our center. Marty Franklin and Jon Abramowitz came after me making up the many generations of her “children.”
For those whom I’ve neglected to mention, forgive me, but the list is too long. My OCD career began in 1979. Her loss is a hole in the fabric of reality, but her legacy and wisdom lives on through all of us whose OCD psychological lineage can be traced back to Edna Foa.
From Marty Franklin, PhD
I am writing this tribute while waiting at an airport gate for a flight to a national conference. Over the course of the next few days I will have the opportunity to present applied research data, participate in a clinical roundtable about OCD and its treatment, & engage with colleagues as we toss around ideas for how best to move the field forward. Edna’s profound influence on my career, my life, and even my thinking is most often accessible during relatively quiet moments like this, where opportunities for reflection make their way forward amidst the work I have committed to myself to doing. Indeed, I learned of Edna’s passing a few weeks ago while right in the middle of presenting a clinical training about exposure-based treatments for OCD. I paused for a moment to take it all in, but before I could decide how best to proceed under the circumstances, I heard Edna’s voice, in her characteristic and unmistakable Israeli accent, telling me that these clinicians took time out of their busy schedules to receive this training, and therefore I must continue straight through to the end. My feelings? You can process those later. Classic Edna.
My very first day of internship in 1991 at the Medical College of Pennsylvania was spent in Edna’s presence at her Center for the Treatment and Study of Anxiety, the unit she established in 1979 to develop, test, and disseminate cognitive-behavioral interventions for anxiety and related conditions. Edna’s work even by then was highly influential, and her legend was already well in the making. At that initial meeting, Edna slid a formidable stack of old-school medical charts across the table to me and said, “Marty, is it? These are your OCD cases for this rotation.” I thanked her, then asked the first of myriad naïve questions in the legendary Tuesday Meetings: “When will I receive the training to treat these cases?” She pivoted back to look at Michael Kozak, her Clinical Director, as if to wax nostalgic about the process of indoctrinating yet another green intern. Edna then gestured at the pile, and said, “The training is in there.” Edna was a fine clinician too, and thus read well my horrified expression, then offered, “But don’t worry: we’ll help you.” True to her word, she did exactly that.
Edna’s influence on the field broadly speaking, on the development and expansion of cognitive-behavioral theory, on using clinical science to alleviate human suffering, and in pushing the proverbial envelope, has been chronicled elsewhere and cannot ever be overstated. Edna was one of the true pillars of clinical psychology, and the effects of her work will live on in perpetuity, of that I have little doubt. What was less well known except for those of us fortunate enough to have been mentored by Edna was the incredible amount of time and emotional investment she made in seeding the field with the next generation of theorists, scholars, and clinicians who would carry that work forward in the years to come. I count myself in that incredibly lucky group, all of whom were blessed by her personal investment in our training and careers. Edna had exacting standards for herself and for us, and fully expected that same level of investment and intensity on our part. Vigorous debate was just part of the process, where occasionally the fur would fly. But Edna also knew us well enough to understand what each of us needed in order to help us make the commitment needed to join her in the vanguard. In one of our many career development conversations back in the mid 1990s, likely in her East Falls office well after 8 pm, I was fretting about the “soft money” environment of academic psychiatry, and openly wondering if it was time to pivot to hard-line academic psychology or even to private practice. Edna stopped my rumination dead in its tracks, looked into the depths of my soul (which she did regularly), and said, “It’s only soft money if you can’t get it…and I know you can get it. Plus, academia is a really fun way to make a living, and a life.” Edna Foa believed in me: it was about damn time to believe in myself as well, and to make the commitment required to honor that belief. And to always keep pushing to get better at the work, which is truly a never-ending process.
Sitting in this airport now, on my way to give another set of talks on topics I have come to know very well and continue to pursue with the passion that comes from also believing that this work is vital, I concur with Edna’s assessment of academia, and am truly grateful that I listened. Thank you, Edna, for illuminating a path forward for me, as I know you did for countless others. You were unforgettable, and your work will continue on in the hands of those you mentored and trained to carry on the legacy.
From Gail Steketee, PhD, MSW
I had the pleasure and helpful educational challenge of training under Dr. Edna Foa beginning in 1976 and continuing for a decade during which I worked closely with her studying OCD and co-authoring manuscripts and federal grant applications. Edna generously provided me with excellent clinical supervision during my training at the Behavior Therapy Unit at Temple University where I learned how to treat phobias, agoraphobia and panic, and especially OCD. Edna’s encouragement and specific feedback guided my understanding of patients and how to provide effective treatment. Her supervision coincided with the end of her important early study of the impact of exposure and response prevention, following in the steps of Victor Meyer, Isaac Marks, and Jack Rachman. I treated the last few patients with OCD in her study and co-authored a case report stemming from that work – my first published paper in the field in 1977.
Edna opened many doors for me to join colleagues around the world who were studying OCD and behavioral treatment methods. Together we wrote and published 26 papers and 14 book chapters. And I mean “together”. We would schedule writing times during which Edna generated ideas and spoke aloud in her heavily accented Israeli English while I contributed my thoughts and sharpened the language as we went along. Grant applications were a special challenge as NIMH became strict about page limits. More than once we stayed up all night writing grants to meet the deadline – we were both younger then – and once we actually drove to Bethesda to deliver a grant application just in time for the deadline. I joined Edna at many conferences in the U.S. (especially AABT [now ABCT] and OCF [now IOCDF]) and in Europe at EABCT and WCBCT (the World Congress of CBT). We met many delightful OCD researchers and clinicians – it was an exhilarating time. I traveled with Edna and friends to her home country of Israel where she treated us to delightful sights and experiences including the Dead Sea.
The 10 year period with Edna was a heady time as my career unfolded. She supported my decision to get a PhD in social work at Bryn Mawr while working full time with her on our research. Eventually, I left Temple to take a full-time faculty position at Boston University, arriving with a strong publication record already in hand thanks to Edna’s masterful training and modeling of how to design and conduct research, how to write papers that accurately reflected the study and its findings, how to write strong grant applications, and how to connect with energizing colleagues around the world. I am grateful for her mentoring that enabled me to establish my own career and become a mentor to others. She was a brilliant theoretician who spawned impressive thinking and research on OCD, PTSD, behavior therapy, and related topics. Hers was a long and full life. She will be sorely missed.
Dr. Judith L. Rapoport has left an indelible mark on the field of obsessive compulsive disorder (OCD) — not only through her extraordinary scientific contributions, but through the compassion, curiosity, and humanity she brought to her work. For countless individuals and families, her legacy is not just measured in research breakthroughs, but in hope restored and lives changed.
At a time when OCD was widely misunderstood, often hidden, and rarely discussed, Dr. Rapoport helped bring it into the light. Through her pioneering work at the National Institute of Mental Health, she gave shape and voice to a condition that many struggled to name. She was among the first to recognize that OCD could affect children, and that these young people deserved understanding, accurate diagnosis, and effective care. This insight alone transformed the trajectory of the field and opened doors for earlier intervention and support for families who had long felt alone.
What set Dr. Rapoport apart was not only her intellect, but her deep commitment to the people behind the science. She approached each question with both rigor and empathy, helping to establish treatments that have since become the gold standard, including exposure and response prevention (ERP) and medication. Her work helped shift the narrative—away from blame or misunderstanding, and toward recognition of OCD as a real, treatable medical condition.
Beyond the lab and clinic, Dr. Rapoport had a rare gift for storytelling. Her book, The Boy Who Couldn’t Stop Washing, brought readers into the lived experience of OCD with clarity and care. For many, it was the first time they saw their own struggles reflected with such honesty and dignity. It helped families feel seen, understood, and less alone — an impact that continues to ripple outward today. The Boy Who Couldn’t Stop Washing impacted professionals as well, providing an eye-opening introduction and gateway to the world of working with OCD.
For these accomplishments and more, Dr. Rappaport received the IOCDF’s 2018 Career Achievement Award. Her influence extends through the many clinicians and researchers she has mentored, each carrying forward her dedication to both excellence and empathy. Through them, her work continues to grow, shaping the future of OCD research and care in ways that are both profound and deeply human.
To honor Dr. Judith Rapoport is to honor a career defined not only by discovery, but by kindness and purpose. She helped the world better understand OCD — but more importantly, she helped people living with OCD feel understood. And in doing so, she changed lives in ways that will endure for generations.
At 51, the mother of four from Wichita Falls, Texas, was busy,
Mary Royal, Patient
tired, and juggling the overlapping demands of work, family, and everyday life. The appointment felt routine—easy to reschedule and easy to dismiss. In a decision that would change everything, she went.
In 2023, Royal was diagnosed with stage 2B multicentric invasive lobular and ductal carcinoma. What followed was a cascade familiar to many cancer patients but deeply personal in its toll: a double bilateral mastectomy, months of chemotherapy and radiation, and the discovery of a nodule in her chest cavity. Another scan later revealed a mass on her ovary, prompting a preventative radical hysterectomy. By the end of the year, Royal had endured positron emission tomography (PET) scans, injections, fasting, and what she called “all that nuclear medicine.”
For many patients, completing treatment is supposed to signal relief. In reality, it often marks the beginning of a new phase—one defined by uncertainty. Surveillance imaging, blood tests, and follow-up visits can feel like checkpoints in an endless waiting game. Every scan carries both hope and fear.
Royal knows this phase well. Like many survivors, she lives with what patients and clinicians call scan anxiety. “I’ve never met a person diagnosed with cancer who did not live with scan anxiety,” she said.
That anxiety eventually led her to consider a different way of monitoring her disease—one that looks not for tumors large enough to be seen on a scan, but for microscopic traces of cancer that may remain in the body after treatment. These traces are known as measurable, or minimal, residual disease (MRD).
MRD basics
MRD refers to the small number of cancer cells that can persist after treatment, even when imaging and conventional tests show no evidence of disease. These cells are often invisible to computed tomography (CT), magnetic resonance imaging (MRI), or PET scans, yet they can drive relapse months or years later.
Historically, MRD testing has been best established in hematologic malignancies such as leukemia, lymphoma, and multiple myeloma. In these diseases, molecular and flow-based techniques can detect one malignant cell among tens of thousands, or even millions, of normal cells. In solid tumors, however, detecting MRD has been far more challenging. That is now changing.
Advances in liquid biopsy technologies allow researchers to analyze circulating tumor DNA (ctDNA): tiny fragments of DNA shed by cancer cells into the bloodstream. With increasingly sensitive assays, it is now possible to detect residual disease at levels far below what imaging can reveal.
MRD matters because cancer recurrence is often a race against time. The earlier residual disease is detected, the greater the opportunity to intervene—whether by intensifying therapy, switching treatments, or, in some cases, sparing patients from unnecessary additional therapy if no disease is detected.
Regulators are taking note. In January 2026, the U.S. Food and Drug Administration (FDA) issued draft guidance supporting the use of MRD negativity as an endpoint in clinical trials for multiple myeloma. The move signaled growing confidence in MRD as a meaningful surrogate for long-term outcomes, potentially accelerating clinical trials and access to new therapies.
Deciding to look closer
When Royal’s oncologist suggested the Personalis NeXT Personal® test, a blood-based MRD assay, her initial reaction was hesitation.
“I said, ‘Let me think about it,’” she recalled. As she researched the test online, her anxiety rose. “I thought, ‘No, thank you. I have had so much anxiety already.’”
Her husband disagreed. “You are insane,” he told her, “Why would you not want to do that?” Her oncologist offered a different perspective: “What is the point of science if we don’t use it?”
“That really resonated with me,” Royal said.
She agreed to the test and had her first ctDNA draw in early 2024. Since then, she has taken it 13 times.
“Seeing that zero in the results is a huge relief,” she said. “I really appreciate how much easier the test is on me, both mentally and physically. Now, I cannot believe anyone would say ‘no’ to this. It brings me so much comfort. And I want to know what to do next. I don’t want to just sit around waiting for something when I have the ability to see things early on.”
Her experience reflects a growing shift in survivorship—from episodic imaging to continuous molecular monitoring.
An ultrasensitive approach
For Richard Chen, MD, CMO at Personalis, the goal of ultrasensitive MRD testing has always been to address the uncertainty patients live with after treatment.
Richard Chen, MD Chief Medical Officer Personalis
“Our NeXT Personal test pioneered ‘ultrasensitive MRD’ down to about one part per million of ctDNA, designed to be a leap forward in detecting very small traces of cancer from a blood sample earlier,” Chen said.
The test is tumor-informed, meaning that it begins with whole-genome sequencing of a patient’s tumor. From that data, up to approximately 1,800 tumor-specific mutations are identified to create a personalized molecular signature. Blood samples are then analyzed for that signature.
“The groundbreaking clinical data that we have published in lung and breast cancer shows that the ultrasensitive capabilities of NeXT Personal enable it to detect cancer many months to years ahead of imaging,” Chen said, “potentially allowing for earlier intervention and treatment of the patient.” Equally important, he added, is the reassurance that a highly sensitive negative result can provide.
Personalis is expanding MRD testing beyond simple detection. A new opt-in feature, the Real-Time Variant Tracker®, allows clinicians and patients to view potentially actionable mutations detected in ctDNA, including those associated with treatment resistance.
MRD testing is increasingly viewed not just as a prognostic tool, but as a way to actively guide care. Chen outlines three major applications: earlier detection of residual or recurrent disease; earlier de-escalation of therapy for patients who have cleared their cancer at a molecular level; and real-time monitoring of treatment response.
“Cancer is often a race against time,” he said. “If you can detect cancer that’s coming back much earlier than before, then you have the opportunity to intervene earlier with additional treatment for the patient.”
Adding biological precision
Sensitivity alone, however, is not the only challenge in MRD detection. Biological precision—understanding which cells persist and why—is equally important.
Zivjena Vucetic, MD, PhD Chief Medical Officer Mission Bio
Zivjena Vucetic, MD, PhD, CMO at Mission Bio, points to the limitations of bulk sequencing approaches, which average signals across mixed-cell populations.
Mission Bio’s single-cell MRD assay simultaneously detects genetic mutations and surface protein expression across thousands of individual cells in acute myeloid leukemia. This approach reveals whether mutations coexist in the same cell and how they relate to cellular phenotypes.
“Our integrated single-cell approach provides a more biologically precise definition of measurable residual disease,” Vucetic said, which might improve risk stratification beyond conventional molecular or flow-based methods.
By identifying rare, therapy-resistant clones, single-cell MRD technologies offer insight into clonal evolution and emerging resistance. This information can guide treatment selection and drug development.
Decentralizing monitoring
Accessibility and turnaround time are also shaping the MRD landscape. For example, QIAGEN is advancing MRD monitoring by pairing tumor-informed assay design with decentralized digital polymerase chain reaction (dPCR), aiming to make longitudinal molecular monitoring faster, more accessible, and more informative for research and drug development.
In June 2025, QIAGEN announced a partnership with Tracer Biotechnologies to integrate Tracer’s tumor-informed assay design with QIAGEN’s QIAcuity dPCR platform. The approach begins with sequencing a patient’s tumor, often leveraging existing next-generation sequencing (NGS) data, to identify somatic mutations. Tracer then designs personalized multiplex dPCR assays to detect ctDNA carrying those mutations in blood samples.
Richard Watts Vice President QIAGEN
Running these assays on QIAcuity enables absolute quantification of rare tumor-derived molecules by partitioning samples into thousands of reactions. According to Richard Watts, vice president of partnering for precision diagnostics at QIAGEN, “The result is a decentralized, high-frequency monitoring solution,” with turnaround times measured in hours to days rather than weeks. He noted that this model significantly reduces cost and logistical complexity compared with centralized NGS-based MRD testing while enabling earlier detection of molecular recurrence, often before radiographic changes are visible.
While currently intended for exploratory research use, the platform has clear implications for oncology drug development. By allowing assays to be run on standard dPCR instruments at clinical trial sites, sponsors can avoid centralized sample shipping, simplify global study design, and more rapidly generate data. Frequent sampling also provides detailed insight into tumor kinetics and treatment response, potentially enabling earlier assessments of drug activity.
Looking ahead, QIAGEN anticipates MRD evolving beyond detection toward biological characterization. Emerging single-cell technologies, supported by QIAGEN’s recent acquisition of Parse Biosciences, could reveal why residual disease persists by distinguishing resistant cell populations and non-genetic resistance mechanisms. Watts emphasized that future clinicians will not only ask whether MRD is present, but “why it persists and which pathways sustain it,” signaling a shift toward more precise, biology-driven intervention strategies.
The expanding ecosystem
Beyond ultrasensitive and single-cell approaches, a growing number of companies are contributing complementary technologies that are broadening how MRD is detected, characterized, and monitored across cancer types.
Twist Bioscience, for example, has developed scalable target enrichment solutions for MRD monitoring that support highly personalized approaches to disease surveillance. Its MRD Rapid 500 Panel enables fast design and manufacture of customized capture panels using silicon-based DNA synthesis. By offering panels that range from dozens to hundreds of tumor-specific probes and fast turnaround times, this approach allows researchers to assess adjuvant treatment response at a genomic level while remaining compatible with established NGS library preparation and hybrid capture workflows.
Whole-genome sequencing-based plasma assays are also playing an expanding role in solid tumor MRD detection. Labcorp offers a plasma-based assay for colorectal cancer that uses whole genome sequencing to identify ctDNA associated with MRD. This approach enables the detection of recurrence at a molecular level before clinical symptoms, biological markers, or radiographic evidence emerge, creating an opportunity for earlier and more proactive intervention.
In hematologic malignancies, ultrasensitive liquid biopsy platforms are demonstrating the ability to dramatically shorten the time required to detect residual disease. For instance, Foresight Diagnostics has developed a ctDNA-based MRD platform that achieves exceptionally high sensitivity across multiple cancers. In patients with large B-cell lymphoma, this approach can detect ctDNA immediately after treatment, rather than waiting for months or even years for disease recurrence to become apparent through PET or CT imaging.
Comprehensive NGS-based MRD solutions are also advancing in myeloid malignancies. Thermo Fisher Scientific offers an integrated research-use testing solution that combines highly sensitive DNA and RNA assays on a single sequencing platform. This enables the simultaneous assessment of single-nucleotide variants, insertions and deletions, and gene fusions alongside streamlined informatics and reporting designed to simplify MRD data interpretation in research settings.
Meanwhile, dPCR continues to play a crucial role in MRD monitoring, where absolute quantification and extreme sensitivity are required. Bio-Rad Laboratories has long supported droplet dPCR technologies that are well suited for tracking low-abundance disease markers. These capabilities are particularly valuable in both hematologic malignancies and solid tumors, where MRD signals in blood can be vanishingly small yet clinically meaningful.
Pre-analytical precision
As MRD assays push detection limits ever lower, pre-analytical steps such as sample collection and cell-free DNA (cfDNA) extraction become increasingly important.
Anagha Kadam, PhD Scientist, NEB
As one example, Anagha Kadam, PhD, applications and product development scientist at New England Biolabs (NEB), highlights how the Monarch Mag Cell-free DNA Extraction Kit addresses crucial challenges in liquid-biopsy workflows and MRD research.
This kit is a magnetic bead-based solution designed for the reproducible isolation of circulating cfDNA from biofluids like plasma, urine, and cerebrospinal fluid. “The kit can be used to isolate cfDNA for discovery and detection workflows, including ctDNA profiling, cancer biomarker discovery, and oncology diagnostics research,” Kadam explained. This technology efficiently recovers cfDNA fragments in the typical sizes of 150–300 base pairs, and even as small as 50 base pairs, while remaining compatible with common anticoagulant and preservative collection tubes. According to Kadam, “The silica-coated magnetic beads, combined with optimized buffer chemistry, help ensure maximum binding and recovery of cfDNA in manual or automation formats.”
Sensitivity and reproducibility are especially crucial for MRD applications. “A cfDNA isolation method that is compatible with different sample types, and that faithfully isolates cfDNA, is a key consideration when establishing MRD workflows,” Kadam noted. She added that the kit delivers “reproducible, high-quality cfDNA yields from different biofluid samples, without additional post-extraction cleanups,” enabling consistent fragment profiles while saving time. When integrated with NEB’s sequencing and amplification tools, the kit supports streamlined, end-to-end workflows for generating high-quality data from challenging clinical samples.
From waiting to watching
For Mary Royal, MRD testing has not eliminated uncertainty, but has transformed it.
Instead of waiting passively for scans, she feels engaged in her care. Instead of fearing every appointment, she has access to information that helps her understand what is happening inside her body in near real time.
“I want to know what to do next,” she said. “I don’t want to just sit around waiting for something when I have the ability to see things early on.”
As MRD technologies continue to mature, the desire to replace waiting with knowledge is becoming central to modern oncology. MRD is no longer just a research endpoint or laboratory metric. It is becoming a bridge between science and survivorship, offering patients, clinicians, and researchers a clearer signal in the noise of uncertainty.
And sometimes, that signal is a simple zero—small, powerful, and profoundly reassuring.
Mike May, PhD, is a freelance writer and editor with more than 30 years of experience. He earned an MS in biological engineering from the University of Connecticut and a PhD in neurobiology and behavior from Cornell University. He worked as an associate editor at American Scientist, and he is the author of more than 1,000 articles for clients that include GEN, Nature, Science, Scientific American, and many others. In addition, he served as the editorial director of many publications, including several Nature Outlooks and Scientific American Worldview.
IntroductionCochlear implant (CI) patients who are single-sided deaf can match the sound quality of speech presented to their CI ear and speech presented to their normal hearing ear. Previous work using this patient population has generated acoustic approximations of CI sound quality for speech, achieving high similarity ratings through interactive manipulation of sound parameters such as filtering, pitch shifting, and spectral smearing. The present study aimed to extend this approach to music.MethodsA digital audio workstation (DAW) methodology was developed for generating sound quality matches to both speech and music in 11 adults with unilateral MED-EL CIs and contralateral acoustic hearing. Participants compared the sound quality created by acoustically manipulated signals presented to their better hearing ear with the sound quality of unprocessed signals presented to the CI ear. The similarity of the two signals was rated on a scale of 1 to 10 with 10 indicating a perfect match.ResultsOn average, speech matches achieved higher similarity ratings (9.3) than music matches (6.7). Speech matches were typically achieved using bandpass filtering, pitch shifts, and distortion. Similarity ratings for speech using the digital audio workstation (9.3) were not different from those (8.7) using the custom, speech-specific software of previous studies. Music matches frequently required additional manipulations, including frequency equalization and modulation. The specific manipulations required varied across participants, and several individuals could not complete music matches despite extensive attempts.DiscussionThese findings suggest that music introduces perceptual dimensions not fully addressed by speech-based matching procedures. The DAW methodology provides an accessible framework for investigating CI sound quality and may guide future efforts to characterize and optimize sound quality for signals beyond speech.
IntroductionSpeech perception in noise (SPiN) is a critical challenge for individuals with sensorineural hearing loss (SNHL), and current behavioral assessments can be unreliable in populations with language barriers or cognitive impairment. Cortical auditory evoked potentials (CAEPs) can serve as a supplementary measurement as they often show strong correlations with SPiN outcomes across diverse hearing profiles.MethodsFollowing PRISMA and SWiM guidelines, this systematic review includes studies from PubMed, Web of Science, and Scopus databases that examined the relationship between non-task related CAEPs and SPiN outcomes in adults with normal hearing, SNHL, or cochlear implants.ResultsSixteen studies were included, encompassing 238 participants with SNHL and 204 participants with normal hearing. Across studies, N1 latency, P2 latency, and N1-P2 amplitude of the onset CAEP and acoustic change complex (ACC) are most consistently correlated with SPiN performance, particularly in sentence-based tests. The mismatch negativity (MMN) showed limited predictive value, as findings varied by age and hearing status. A meta-analysis was not conducted due to methodological heterogeneity.ConclusionOnset CAEP and ACC N1 and P2 latencies together with N1-P2 amplitudes particularly demonstrate potential as electrophysiological indicators of SPiN performance. Their clinical utility is promising for populations where behavioral testing can be unreliable, such as CI users or individuals with cognitive or language barriers. However, standardization of protocols and further longitudinal research are needed to validate their application in clinical settings.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD42023404158, identifier PROSPERO (CRD42023404158).
Electrotactile feedback via transcutaneous interferential electrical stimulation generates temporally modulated stimulation fields and enables frequency-domain adjustment with carrier and beat frequencies. To systematically characterize these effects, we present a simulation framework that integrates tissue-scale electrical potential simulation with the finite element method and axon-scale dynamics using the axon cable equation, which incorporates cable theory and the Hodgkin–Huxley model, to predict axon activation and tactile perceptual metrics. We simulated a simplified glabrous skin model with three orthogonally oriented axons. Results show that the carrier frequency in the range of 1–4 kHz determines the upper bounds of the perceived field size, reaching up to 1.6 mm and exceeding the 1 mm electrode diameter, and perceived intensity, whereas the beat frequency in the range of 0–100 Hz adjusts these quantities within these bounds. Furthermore, axons oriented perpendicular to the skin surface exhibit lower activation thresholds than those oriented parallel. Unlike the conventional approaches of transcutaneous electrical stimulation, our results suggest that transcutaneous interferential electrical stimulation can shape the perceived field and perceived intensity without electrode reconfiguration or amplitude modulation. These findings clarify the distinct roles of carrier and beat frequency in tactile perception. This paper provides a theoretical foundation for frequency-domain adjustment of electrotactile interfaces and points toward compact, programmable systems. Quantitative validation through psychophysical experiments will further test and refine these predictions.
IntroductionThere has been growing recognition of potential differences in disease course and presentation between men and women with MS. This study examined sex differences in MS using data collected at study entry in the Swiss Multiple Sclerosis Cohort (SMSC).MethodsA cross-sectional analysis of the data from 1541 SMSC participants (June 2012–February 2022) with persons with relapsing-remitting MS or Clinically Isolated Syndrome (named relapsing type) and progressive MS including persons with Primary Progressive Multiple Sclerosis (PPMS) and Secondary Progressive Multiple Sclerosis (SPMS) was performed. Sociodemographic and clinical characteristics, disease history, and severity indicators were examined, focusing on sex differences within progressive and relapsing MS types, and comparing these MS types. Statistical analyses included Mann-Whitney U tests and chi-squared tests for group comparisons. Multivariate linear regression models were constructed to examine the independent association of sex with Expanded Disability Status Scale (EDSS) scores, adjusting for age, disease duration, treatment category, recent relapse, and body mass index (BMI).ResultsWomen represented 65.8% of the cohort (1,014/1,541). BMI was significantly lower in women than in men in the relapsing type and SPMS (relapsing: p < 0.001; SPMS: p = 0.001; PPMS: p = 0.86). Age at first symptoms differed by sex depending on MS type: women were younger in the relapsing group (29.7 vs. 31.4 years, p = 0.036), while men were younger in PPMS (42.3 vs. 47.7 years, p < 0.001), with no difference in SPMS (p = 0.5). In univariate analysis, men showed a trend toward higher disability levels at study entry in the relapsing type (p = 0.058), but no significant sex differences in EDSS were observed in progressive forms. In multivariate analysis, female sex showed a trend toward lower EDSS scores in relapsing MS after adjusting for clinical factors (β = −0.13, 95% CI: −0.26 to 0.005, p = 0.059) but was not associated with EDSS in PPMS (β = −0.09, p = 0.802) or SPMS (β = + 0.09, p = 0.816).ConclusionThis study identified sex differences in disease distribution, BMI and EDSS at their entry in the SMSC. These findings underscore the complexity of sex differences in MS and highlight the importance of prospective longitudinal studies with standardized severity assessments to clarify sex-specific disease trajectories and inform personalized treatment strategies.
