Category: 8. Health

Antimicrobial resistance (AMR) is one of the most urgent public health challenges in 2025. This phenomenon occurs when microorganisms such as bacteria, viruses, fungi, and parasites evolve resistance to drugs that were once effective. According to the CDC’s 2025 report, AMR could lead to as many as 10 million deaths annually by 2050, overtaking major diseases like cancer.

AMR stems from the natural evolutionary ability of microbes to survive selective pressure from antimicrobials. This process is significantly accelerated by the overuse and misuse of these drugs in human health, veterinary medicine, and agriculture. Resistant infections often require longer treatment courses, are associated with increased disability and mortality, and lead to extended hospital stays and higher healthcare costs — placing a growing burden on health systems and global economies.

The CDC estimates at least 2.8 million resistant infections and over 35,000 related deaths annually in the US alone.

Resistance Mechanisms

AMR typically arises through two primary mechanisms: spontaneous genetic mutations and horizontal gene transfer (via conjugation, transformation, or transduction).

Recent findings outline several well-characterized resistance pathways:

• Target modification: Structural alterations in drug targets — often key proteins or cell components — can prevent effective drug binding.
• Enzyme production: Certain bacteria produce enzymes such as beta-lactamases that deactivate antibiotics like penicillins and cephalosporins. These enzymes are increasingly common in gram-negative species such as Escherichia coli and Klebsiella pneumoniae.
• Efflux pumps and permeability barriers: Some bacteria limit drug entry or actively expel antibiotics using multidrug efflux pumps. This is particularly problematic in gram-negative organisms due to their additional outer membrane.

These resistance mechanisms can coexist within a single organism, giving rise to “pan-resistant” strains that are unaffected by nearly all available antimicrobial agents.

Resistance can emerge rapidly — even during the course of treatment — turning previously susceptible infections resistant mid-therapy and narrowing treatment options dramatically.

Recent Trends and Global Data

New international data highlight the accelerating spread of AMR, with particularly concerning developments across both bacterial and fungal pathogens.

The World Health Organization (WHO)’s 2024 Bacterial Priority Pathogens List documented rising resistance rates in K pneumoniae and E coli, especially in Asia and Africa — regions where therapeutic options remain severely limited. These findings align with projections from a 2024 commentary published in The Lancet, which estimates that AMR could cause up to 10 million deaths annually by 2050, disproportionately affecting low- and middle-income countries.

In the US, the CDC reported that more than 35% of hospital-acquired urinary tract infections in 2024 were caused by multidrug-resistant (MDR) organisms. This surge is driven in large part by the horizontal transmission of resistance genes via mobile genetic elements such as plasmids and transposons.

MDR tuberculosis also continues to pose a serious global health threat. Data from Eastern Europe and parts of Asia show that over 20% of new tuberculosis cases now involve MDR strains. These cases require longer, more toxic regimens and are associated with poorer clinical outcomes, adding further strain to public health systems.

Fungal resistance is emerging as a parallel crisis. A recent review reported that more than 90% of Candida auris isolates collected from hospitals in Europe and North America were resistant to multiple antifungal agents. This poses a serious risk to patients who are immunocompromised and critically ill, particularly in ICUs where infection control remains challenging.

Despite the growing threat, treatment pipelines remain thin. While several new antimicrobial agents are under investigation, most remain in preclinical or early clinical stages. The report underscores an urgent need for sustained investment in antimicrobial drug development to replenish a shrinking therapeutic arsenal.

Adding to the concern, recent studies describe the emergence of novel resistance mechanisms in gram-positive pathogens such as methicillin-resistant Staphylococcus aureus. Some strains have developed traits that compromise the efficacy of even newly approved agents — further complicating treatment strategies and escalating costs of care.

As AMR continues to evolve across multiple fronts, these findings reinforce the need for comprehensive, coordinated strategies to monitor resistance patterns; support antimicrobial stewardship; and accelerate therapeutic innovation.

Economic Toll

The global economic impact of AMR could be staggering. The 2024 Lancet commentary projects that AMR could result in up to $100 trillion in economic losses by 2050. The burden is expected to fall disproportionately on low- and middle-income countries, where weaker health systems and limited access to effective therapies could exacerbate existing disparities in both health outcomes and economic development.

Clinical consequences are already evident in hospitals around the world. Recent research shows that resistant healthcare-associated infections — such as bloodstream infections and ventilator-associated pneumonias — are associated with mortality rates approaching 30% higher in patients in resource-limited settings. Contributing factors include poor hospital infrastructure, limited access to diagnostics and therapeutics, and inadequate infection control measures.

Meanwhile, a 2024 review highlights the growing threat of hospital-acquired infections caused by Acinetobacter baumannii and Pseudomonas aeruginosa — both of which exhibit high levels of resistance to multiple antibiotic classes. Without effective interventions, these infections may become increasingly difficult, if not impossible, to treat, further driving up hospital mortality and straining intensive care resources.

Emerging Strategies and Solutions

Several promising strategies are being explored to slow AMR progression and strengthen the clinical response.

• Development of new antimicrobials: Recent research highlights novel compounds designed to overcome common resistance mechanisms. While early in development, these agents may offer new hope against multidrug-resistant pathogens.
• Alternative therapies: Early-phase studies suggest that bacteriophage therapy and antibacterial nanoparticles could serve as complementary approaches to combat infections that no longer respond to conventional treatments. These technologies are gaining traction but require rigorous clinical validation.
• Antimicrobial stewardship and surveillance: Effective stewardship programs remain central to the AMR response. Core components include the rational prescribing of antimicrobials, real-time infection surveillance, and access to rapid diagnostic tools for antimicrobial susceptibility testing.
• Education and global awareness: The WHO and CDC continue to emphasize the need for coordinated global education campaigns to promote the appropriate use of antimicrobials and curb self-medication — particularly in countries with weak regulatory oversight.
• National initiatives: In Spain, the 2025-2027 Plan Nacional frente a la Resistencia a los Antibióticos (National Plan against Antibiotic Resistance) stands out as a model. The plan includes enhanced epidemiologic surveillance, increased funding for antimicrobial research, ongoing training for healthcare providers, and public education campaigns. It also calls for integrated action across all levels of the health system to ensure a coordinated national response.

Conclusions

AMR is no longer a looming threat — it is a present-day global health emergency. Its continued spread is undermining the foundations of modern medicine, with far-reaching consequences for clinical care, public health, and global equity.

As resistance mechanisms become increasingly complex and widespread, the therapeutic arsenal is shrinking — particularly in hospital settings and for vulnerable populations. Meanwhile, antibiotic development continues to lag, with most new agents stalled in early-phase research.

To avoid a future where routine infections become untreatable, the global response must be ambitious and coordinated. Expanding antimicrobial stewardship, accelerating drug development through sustained investment, and enforcing rational prescribing practices are all urgent priorities. These efforts must be anchored in the One Health approach, which recognizes the interconnectedness of human, animal, and environmental health.

Education and behavior change are equally essential. Clinicians, patients, and policymakers all play a role in preserving the effectiveness of existing antimicrobials. And while emerging therapies such as phage therapy, nanomedicine, and immunomodulation offer hope, they require rigorous testing and clear regulatory pathways before they can be integrated into clinical practice.

The window for action is narrowing — but meaningful progress is still possible. With global alignment, scientific innovation, and sustained commitment, the trajectory of AMR can be reversed.

This story was translated from El Médico Interactivo.

Hi, it’s Amber in Hong Kong, where less than half of eligible women get their recommended cervical cancer screening. If only the procedure was less unpleasant …

As someone who has reported on cancer research for some years, I’ve long known that cervical cancer is one of the most preventable cancers, thanks to vaccination and early screening. Yet, I must confess I’ve never received a screening for HPV, the human papillomavirus that’s the primary cause of cervical cancer. The thought of a Pap smear makes me squirm.

An additional six million new HIV infections and four million AIDS-related deaths could occur between 2025 and 2029 if US-supported HIV treatment and prevention services collapse, according to UNAIDS.

“This is not just a funding gap. It’s a ticking time bomb,” said UNAIDS Executive Director Winnie Byanyima at the launch of the organisation’s 2025 global AIDS update on Thursday. 

“We have seen services vanish overnight. Health workers have been sent home. And people – especially children and key populations – are being pushed out of care.” 

“Key populations” refer to people most vulnerable to HIV infection, including sex workers, men to have sex with men, people who inject drugs and young women.

Some of the immediate effects of the US withdrawal of funds since Donald Trump assumed the presidency in January include the closure of health facilities, healthworker job losses, and disrupted treatment, testing and prevention services.

The US President’s Emergency Plan for AIDS Relief (PEPFAR) had committed $4.3 billion in bilateral support in 2025 and “those services were stopped overnight when the US government shifted its foreign assistance strategies,” notes the UNAIDS report. 

PEPFAR had supported HIV testing for 84.1 million people and HIV treatment for 20.6 million people.

“Disruptions are being felt across the HIV response and pose a huge risk of increased mortality, a surge of new HIV infections, and the development of resistance to the most commonly used treatment regimens.”

In Mozambique, for example, over 30,000 health personnel have lost their jobs.

UNAIDS itself faces huge job losses, and is reducing its Geneva head office staff from 127 to a mere 19 employees, according to a report this week by Geneva Solutions.

The UN agency’s restructuring plan will cut staff by 54% globally, leaving 280 staff worldwide. 

HIV prevention programmes hit hard

External funding financed almost 80% of HIV prevention in sub-Saharan Africa, 66% in the Caribbean and 60% in the Middle East and North Africa, according to UNAIDS.

PEPFAR alone reached 2.3 million adolescent girls and young women with comprehensive HIV prevention services in 2024 and enabled 2.5 million people to use pre-exposure prophylaxis (PrEP). Many of these programmes have now stopped completely, according to UNAIDS. 

PrEP involves taking medication to prevent HIV infection and is usually taken by people at high risk of infection, and PEPFAR funded over 90% of PrEP initiations globally in 2024.

“Countries are reporting limited availability of PrEP and reduced activities to prevent new HIV acquisitions, including among adolescent girls and young women,” said UNAIDS.

In Nigeria, budget cuts have reduced PrEP initiation from 40,000 to 6000 people per month.

At the end of 2024, just before a sudden collapse in funding, new HIV infections had been reduced by 40% and AIDS-related deaths by 56% since 2010, Byanyima notes in the report. Countries had also reduced the annual number of children acquiring HIV from their mothers by 62% to 120,000 since 2010.

However, prevention efforts were already flatlining before the withdrawal of US aid. In 2024, there were 1.3 million new infections, which was almost the same as the year before.

“Over 210,000 girls and young women aged 15 to 24 acquired HIV in 2024 – an average of 570 new infections every day,” according to the UNAIDS report.

In 2024, 630,000 people died from AIDS-related causes, 61% of them in sub-Saharan Africa. “Community-led services, which are vital to reaching marginalised populations, are being defunded at alarming rates,” said UNAIDS.

“In early 2025, over 60% of women-led HIV organisations surveyed had lost funding or were forced to suspend services.”

Domestic budgets inadequate

Only 25 of the 60 low- and middle-income countries included in the report have increased their domestic budgets for HIV in 2026. The average increase amounts to 8%, approximately $180 million in additional domestic resources. 

“This is promising, but not sufficient to replace the scale of international funding in countries that are heavily reliant,” UNAIDS notes.

“It is important for donors to recognize that the option of increasing domestic HIV funding is not immediately or equally available to all countries,” UNAIDS notes.

“Combinations of debt distress, slow economic growth and underperforming tax systems leave many countries, notably in sub-Saharan Africa, with limited fiscal space to increase their domestic funding for HIV. “

It cites the recent International Conference on Financing for Development in Seville in Spain, as offering a way forward with “calls for debt relief, international tax cooperation and reform of international financial institutions”.

These measure would provide “the first steps towards a new economic settlement that can give countries the fiscal space needed to invest in the global HIV response”, UNAIDS notes.

“Urgent action and revived solidarity are needed to sustain the progress made and prevent a resurgence of HIV.”

Image Credits: UNAIDS.

Trends in SGLT-2 inhibitor prescriptions by purpose

Supplementary Fig. 2 illustrates the trend of the average monthly prescription volume by year, categorized according to the purpose of SGLT-2 inhibitor prescriptions. Of the 6787 patients analyzed, 5805 (85.5%) were prescribed SGLT-2 inhibitors for DM, 550 (8.1%) for CKD, and 432 (6.4%) for HF. Prescriptions have been rapidly increasing since 2018, with the number of prescriptions in 2023 being approximately 7.4 times higher than in 2018. Additionally, both CKD and HF prescriptions exhibited a marked rise from 2020 onward.

Baseline characteristics and prevalence of erythrocytosis

Among the 6787 patients included in this retrospective study at Bundang Seoul National University Hospital, 1145 (16.9%) developed erythrocytosis after initiating SGLT-2 inhibitor therapy, while 5642 (83.1%) did not. The median follow-up was 530 days (IQR, 277–981 days) for the overall cohort and 773 days (IQR, 445–1305 days) for the erythrocytosis subgroup. Table 1 summarizes the baseline characteristics of the study population, stratified by the presence of erythrocytosis. Patients with erythrocytosis were significantly younger, with only 11.2% being ≥ 70 years of age compared to 37.5% in the non-erythrocytosis group (p < 0.001). Males were more prevalent in the erythrocytosis group (88.9% vs. 60.0%, p < 0.001). A higher proportion of patients with erythrocytosis had a BMI ≥ 25 kg/m² (63.9% vs. 48.1%, p < 0.001). Regarding comorbidities, DM was more frequent in patients with erythrocytosis (89.9% vs. 85.4%; p < 0.001). In contrast, comorbidities including hypertension (HTN), dyslipidemia (DL), HF, CKD, coronary artery disease (CAD), cerebrovascular accident (CVD), peripheral artery disease (PAD), and chronic obstructive pulmonary disease (COPD), were more prevalent in the non-erythrocytosis group (all p < 0.001).

Current smoking (40.0% vs. 15.7%) and alcohol consumption (35.2% vs. 19.5%) were more prevalent in the erythrocytosis group (both p < 0.001). SGLT-2 inhibitor type did not differ (p = 0.590), with dapagliflozin most common (57.2%). Antiplatelet use was less frequent in the erythrocytosis group (36.3% vs. 41.9%; p = 0.001), while anticoagulation was similar (12.1% vs. 11.4%, p = 0.516). Baseline erythrocytosis was significantly more common in the erythrocytosis group than in the non-erythrocytosis group (26.6% vs. 1.2%; p < 0.001). In the analysis excluding patients with baseline erythrocytosis (n = 372), the incidence of erythrocytosis was 13.1% (n = 840/6415).

Multivariable analysis of risk factors for erythrocytosis

To address the potential impact of baseline erythrocytosis, a sensitivity analysis was performed by excluding patients with baseline erythrocytosis (n = 372). The remaining cohort (n = 6415) was analyzed for erythrocytosis risk factors. Multivariable analysis identified several risk factors for erythrocytosis (Table 2). Male sex (OR 3.24, 95% CI 2.47–4.26), BMI ≥ 25 kg/m² (OR 1.97, 95% CI 1.63–2.39), and current smoking (OR 2.41, 95% CI 1.96–2.96) were strongly associated with increased risk (all p < 0.001). Conversely, age ≥ 70 years (OR 0.46, 95% CI 0.35–0.59), HTN (OR 0.71, 95% CI 0.58–0.86), DL (OR 0.67, 95% CI 0.55–0.81), and CKD (OR 0.51, 95% CI 0.40–0.66) were associated with reduced risk. PAD, and COPD also showed protective effects (Table 2).

Effect of SGLT-2 inhibitors on hematologic parameters

Figure 1 illustrates the changes in Hb and Hct from baseline to peak levels in the total cohort. The median Hb increase for the entire cohort was 1.0 g/dL (IQR, 0.4–1.8 g/dL, p < 0.001), and the median Hct increase was 3.5% (IQR, 1.4–5.7%, p < 0.001). The median time to peak Hb was 210 days (IQR, 109–434 days) following SGLT-2 inhibitor initiation. Compared to baseline Hb and Hct, peak Hb and Hct showed a statistically significant increase, indicating a significant hematologic response to SGLT-2 inhibitor therapy, consistent with the known erythropoietic effects of these agents. Figure 2 shows that the change in Hb levels significantly differs based on the purpose of treatment (p < 0.05). CKD patients showed a median Hb increase of 0.9 (IQR, 0.3–1.6), while DM patients had a median increase of 1.0 (IQR, 0.4–1.7). HF patients exhibited the highest median Hb increase at 1.3 (IQR, 0.5–2.1). This indicates that HF patients experienced the most significant rise in Hb levels, whereas CKD patients showed the lowest increase. Patients without baseline erythrocytosis exhibited significantly greater Hb changes compared to those with erythrocytosis (p < 0.05). The median Hb change was 1.1 (IQR, 0.4–1.8) in patients without erythrocytosis, whereas it was 0.3 (IQR, -0.4–0.8) in those with erythrocytosis (Fig. 3). Table 3 summarizes the hematologic parameters at baseline and peak levels for the total cohort (n = 6787), stratified by sex. Significant sex differences were observed in both baseline and peak Hb and Hct levels, with males consistently exhibiting higher values than females.

Among patients with erythrocytosis (n = 1145), the median hemoglobin increase was 1.4 g/dL (IQR, 0.8–2.2), and the median hematocrit increase was 4.7% (IQR, 2.7–6.8). The median time to peak hemoglobin was 361 days (IQR, 161–634). Serial Hb changes were assessed over 12 months in 769 patients receiving SGLT-2 inhibitors with at least 12 months of Hb follow-up data (Fig. 4). Hb levels rose rapidly within the first 3 months, followed by a more gradual increase, maintaining an overall upward trend over the 12-month period.

Of the 6787 patients, 4756 (70.1%) continued treatment, 944 (13.9%) were lost to follow-up or referred out, and 1087 (16.0%) discontinued treatment. Among the 983 patients with known reasons for discontinuation (excluding 104 patients with unknown reasons), the most common were poor DM control (34.7%), side effects other than erythrocytosis (32.2%), and diabetes medication reduction (14.3%), with erythrocytosis accounting for only 5 (0.5%) discontinuations.

Among patients who developed erythrocytosis while using SGLT-2 inhibitors, hematology consultations occurred in 18 (1.6%) patients, with median serum erythropoietin (EPO) levels of 12.5 mIU/mL (range 7.1–17.61 mIU/mL, reference 2.59–18.50 mIU/mL). Of these, 10 (55.6%) underwent JAK2 mutation testing, 4 (22.2%) had bone marrow examinations, 2 (11.1%) received phlebotomy, and 2 (11.1%) were prescribed aspirin. Four patients discontinued SGLT-2 inhibitors: two due to erythrocytosis (one resolved spontaneously, and one improved with phlebotomy) and two due to well-controlled diabetes (Supplementary Fig. 3).

Thrombosis risk factors

Among the 6787 patients, 0.5% (33 patients) developed thrombosis during the treatment period with SGLT-2 inhibitors (Table 4). HF was more common in the thrombosis group (33.3% vs. 19.5%, p = 0.046), as were antiplatelet use (63.6% vs. 40.8%, p = 0.008), anticoagulant use (36.4% vs. 11.4%, p < 0.001), and baseline erythrocytosis (15.2% vs. 5.4%, p = 0.032). Other factors, including age ≥ 70 years, sex, BMI, eGFR, most comorbidities (e.g., DM, HTN. CAD), smoking, and alcohol use, showed no significant differences between groups.

Antiplatelet agent use (OR 3.57, 95% CI 1.60–7.97, p = 0.002), anticoagulant use (OR 5.93, 95% CI 2.60–13.57, p < 0.001), and baseline erythrocytosis (OR 3.75, 95% CI 1.41–9.96, p = 0.008) were significantly linked to an increased risk of thrombosis in multivariable analysis (Table 5).

Among 33 patients, five patients had erythrocytosis at the time of the thrombosis event and had experienced at least one episode of erythrocytosis within the preceding six months. Notably, all five patients exhibited arterial thrombosis without any venous thrombosis events. However, these five patients also had underlying conditions (atrial fibrillation, severe coronary calcification, large artery atherosclerosis) associated with their thrombosis events, making it unlikely that the thrombosis events were directly related to erythrocytosis. Thrombotic events occurred in 1.8% (n = 21) of the erythrocytosis group, compared with 0.2% (n = 12) in the non-erythrocytosis group (p < 0.001). Within the erythrocytosis group, peak Hb levels were stratified into tertiles: low (16.1–16.9 g/dL), medium (16.9–17.5 g/dL), and high (17.5–22.0 g/dL). Thrombosis rates were 1.4% (n = 6), 2.2% (n = 8), and 2.0% (n = 7), respectively (p = 0.649), suggesting no clear dose–response relationship between Hb levels and thrombosis.

People at higher risk of HIV, such as gay men and people who inject drugs, are facing record levels of criminalisation worldwide, according to UNAids.

For the first time since the joint UN programme on HIV/Aids began reporting on punitive laws a decade ago, the number of countries criminalising same-sex sexual activity and gender expression has increased.

In the past year, Mali has made homosexuality a criminal offence, where the law previously only banned “public indecency”, and has also criminalised transgender people. Trinidad and Tobago’s court of appeal has overturned a landmark 2018 ruling that decriminalised consensual same-sex relations, reinstating the colonial-era ban. In Uganda, the 2023 Anti-Homosexuality Act has “intensified the proscription of same-sex relations”, and Ghana has moved in a similar direction with the reintroduction of legislation that would increase sentences for gay sex.

The crackdown on gay rights comes as the fight against HIV/Aids has been hit by abrupt US funding cuts, which have combined with “unprecedented” humanitarian challenges and climate crisis shocks to jeopardise hopes of ending the global epidemic this decade, UNAids said.

Several groups of people, known as “key populations”, are more likely to be infected with HIV. They include sex workers, gay men and other men who have sex with men, people who inject drugs, transgender people, and those in prisons and other enclosed settings.

In 2025, only eight of 193 countries did not criminalise any of those groups or behaviours, or criminalise non-disclosure of HIV status, exposure or transmission, according to the report.

The number of people infected by HIV or dying from Aids-related causes in 2024 was the lowest for more than 30 years, according to the UNAids annual report, at 1.3 million and 630,000 respectively.

Progress was uneven – ranging from a 56% fall in infections since 2010 in sub-Saharan Africa to a 94% increase in the Middle East and North Africa. But coupled with scientific advances – such as twice-yearly drugs to prevent infection – the world had the “means and momentum” to end Aids as a public health threat by 2030, an internationally agreed goal, it said.

However, that has been “seriously jeopardised” in the early months of this year after sweeping US aid cuts that could undo decades of progress. In January, Donald Trump cut funding that had underpinned much of the global HIV response almost overnight.

The report highlights HIV-prevention services as an area of concern, with many particularly reliant on donor funding. The reported number of people receiving preventive drugs in Nigeria in November 2024 was approximately 43,000. By April 2025, that number had fallen to below 6,000.

Activists say access to prevention will be a particular issue for key populations, who may not be able to access mainstream healthcare due to factors such as stigma or fear of prosecution, but relied on donor-funded community clinics that have now closed.

Key populations were “always left behind”, said Dr Beatriz Grinsztejn, president of the International Aids Society (IAS).

The report is being released before an IAS conference next week in Kigali, Rwanda, where researchers will share data on the impact of cuts.

Modelling by Bristol University calculated that a one-year halt in US funding for preventive drugs in key populations in sub-Saharan Africa would mean roughly 700,000 people no longer used them, and lead to about 10,000 extra cases of HIV over the next five years.

UNAids modelling suggests that without any replacement for funding from US Pepfar (president’s emergency plan for Aids relief), an additional 4m deaths and 6m new infections could be expected globally by 2029.

However, Winnie Byanyima, executive director of UNAids, said 25 of the 60 low- and middle-income countries included in the report had found ways to increase HIV spending from domestic resources to 2026. “This is the future of the HIV response – nationally owned and led, sustainable, inclusive and multisectoral,” she said.

Humans can’t regenerate heart muscle damaged by disease, but scientists have long known that some animals, such as zebrafish, can.

Researchers have now identified a set of genes in zebrafish that reactivate after damage to the heart and patch it up like new, pointing the way to therapies that could reactivate similar genes in humans and jump-start repair of the heart and perhaps other tissues after injury.

The scientists from the University of California, Berkeley, and California Institute of Technology are still working to uncover which upstream gene or genes trigger reactivation of this gene circuit, which normally operates only during development in the embryo. But, once they do, it may be possible to use CRISPR tools to reactivate similar genes in humans after heart damage, since we employ the same set of genes as zebrafish to build the heart during embryonic development.

“Zebrafish and humans are comparable in their cell types and how these cell types form during development, but a major difference in evolution is that adult zebrafish can regenerate many different structures, including their heart, after substantial injury, whereas humans can’t,” said Megan Martik, a UC Berkeley assistant professor of molecular and cell biology. “How can we harness what nature’s already figured out how to do in the zebrafish and apply it in a human context?”

Martik and Marianne Bronner, a Caltech professor of biology and director of the Beckman Institute, are senior authors of a paper about the findings that appeared June 18 in the journal Proceedings of the National Academy of Sciences. The research was led by UC Berkeley graduate students Rekha Dhillon-Richardson and Alexandra Haugan, who are co-first authors of the paper.

The heart is made up of many kinds of cells that comprise muscle, nerve and blood vessel tissue. A portion of these heart cells — in zebrafish, around 12 to 15% — originate from a specific population of stem cells called neural crest cells. Humans have analogous neural crest cells that give rise to varied cell types in almost every organ of the body, ranging from the facial skeleton to the nervous system. Disruption of neural crest cells during development leads to heart defects similar to those found in common congenital heart disorders.

For some reason, zebrafish and a few other animals retain the ability as adults to rebuild tissues derived from the neural crest — the jaw, skull and heart, for example — while humans have lost that ability. These animals are not merely repairing damaged tissue, however. In the heart, cells around an injury revert to an undifferentiated state and then go through development again to make new heart muscle, or cardiomyocytes.

“In both humans and zebrafish, we know that neural crest cells contribute to the heart and that they develop very similarly. But something about them is inherently different on the gene regulatory network level, because the neural crest-derived cardiomyocytes in the zebrafish can respond to injury by regenerating and the same cells in humans can’t,” Martik said.

CRISPR therapy

In the newly reported research, the scientists used single-cell genomics to profile all the genes expressed by developing neural crest cells in zebrafish that will differentiate into heart muscle cells. They then pieced together the genes expressed after they snipped away about 20% of the fish’s heart ventricle. This procedure seemed not to affect the fish, and after about 30 days their hearts were whole again.

By knocking out specific genes with CRISPR, they identified a handful of genes that were essential to reactivation after injury, all of which are utilized during embryonic development to build the heart. One in particular, called egr1, seems to activate the circuit first and perhaps triggers the others, suggesting a potential role in regeneration.

“Differentiated cell types revert back to more of an embryonic gene expression profile and then go through development again,” she said. “What we’ve shown in this paper is that when they do that, they activate this set of genes we know is really important for development of this population of cardiomyocytes.”

The researchers also identified the enhancers that turn on these genes. Enhancers are promising targets for CRISPR-based therapies, since they can be manipulated to dial up or down the expression of the gene.

Martik continues to explore the gene circuit involved in regeneration in zebrafish, and has also developed CRISPR techniques to target gene enhancers in heart-like organoids derived from human heart cells. The tiny organoids, called cardioids, are grown in a dish and develop scars similar to normal heart muscle, allowing her team to manipulate the genes involved in repair.

Should she and her colleagues come up with a therapeutic approach, she has a vision that other cells derived from neural crest cells — such as in the jaw or the peripheral nervous system, among others — could be kicked into high gear to stimulate repair.

“There are so many advances, especially here on campus, in terms of CRISPR therapeutics that if we find the switch that can activate the necessary gene programs to drive regeneration in an organism that can regenerate, then I think it’d be completely feasible to develop a CRISPR therapeutic to drive regeneration in a human-derived context,” Martik said. “I think Berkeley is the only place something like this can be done.”

Reference: Dhillon-Richardson RM, Haugan AK, Lyons LW, McKenna JK, Bronner ME, Martik ML. Reactivation of an embryonic cardiac neural crest transcriptional profile during zebrafish heart regeneration. Proc Natl Acad Sci USA. 2025;122(25). doi: 10.1073/pnas.2423697122

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Dana-Farber Cancer Institute experts report findings from a literature review that rates of early onset gastrointestinal cancers are rising rapidly, with the youngest groups experiencing the highest rise in rates. These alarming rises apply not just to colorectal cancer, but also to pancreatic cancer, esophageal and stomach cancers, as well as rarer gastrointestinal cancers of the appendix, biliary cancer, and neuroendocrine tumors. 

The number of newly diagnosed cases of early onset gastrointestinal cancers rose by 14.8% between 2010 and 2019, according to the review. The rise in early onset cases disproportionately affects people who are Black, Hispanic, of Indigenous ancestry, and women.

“Early onset colorectal cancer has received attention because it was one of the first gastrointestinal cancers to be identified as having a significant shift in the demographic profile of the disease, and because it is the most common early onset gastrointestinal cancer. Historically, colorectal cancer was primarily diagnosed in adults in their 60s and 70s, but in the 1990s a rising incidence in younger populations was first reported,” said senior author Kimmie Ng, MD, MPH, director of the Young-Onset Colorectal Cancer Center at Dana-Farber. “This study takes a wider view and shows that other gastrointestinal cancers are also rapidly rising in young people, including pancreatic cancer, esophageal and gastric cancer, and other rare GI cancers.”

The count of young onset gastrointestinal cases is highest in the oldest group – people aged 40 to 49 – but the rise in rates is progressively steeper in younger groups. For example, people born in 1990 are twice as likely to develop colon cancer and four times as likely to develop rectal cancer compared to those born in 1950, according to the authors.

The authors also note that recent data from the Centers for Disease Control and Prevention (CDC) indicated a more than tripling of the incidence of colorectal cancer in people aged 15 to 19 and a near doubling in people aged 20-24.

The review was published today in the British Journal of Surgery.

What is driving the rising rates of early onset gastrointestinal cancers?

It is not clear what is driving the rising rates of gastrointestinal cancers in young people, but there are common risk factors across gastrointestinal cancers. Factors that people can manage with lifestyle changes include obesity, a sedentary lifestyle, the consumption of processed foods, alcohol use, and smoking. According to the study, heavy alcohol use doubles the risk of gastric cancer, and obesity nearly doubles the risk of colorectal and pancreatic cancers. Smoking also increases the risk of these cancers.

“One of the best things you can do for your health is to stop smoking,” said co-first author Sara Char, MD, a medical oncology fellow at Dana-Farber. “Reducing alcohol use and incorporating lifestyle changes such as getting regular excise and minimizing processed foods are also positive choices.”

Conditions such as fatty liver disease, diabetes, and acid reflux also can increase the risk of different gastrointestinal cancers. “It is important for patients to stay up to date with primary care and to be actively engaged in preventive medicine related to these and other risk factors,” said Char.

The researchers found that inherited genetic mutations that increase the risk of gastrointestinal cancers were more common among people with early onset cancers compared to average onset cancers. But most early onset cancers were not associated with an inherited mutation and instead occurred from a mutation that occurred sporadically, likely triggered by an environmental factor.

“Lifestyle factors such as obesity, a Western-pattern diet including a lot of processed foods, and a sedentary lifestyle are likely contributing to a lot of early onset cases,” said co-first author Catherine O’Connor, a medical student at Harvard Medical School.

How are screening and treatment of gastrointestinal cancers changing?

Screening for colorectal cancer begins at age 45, recently lowered from age 50 due to rising rates of early onset disease. People with a family history of the disease or of pre-cancerous polyps removed during screening colonoscopy may be eligible for screening at age 40 or 10 years prior to their relative’s first polyp or cancer diagnosis.

“It is helpful for people to know if they have a family history that includes colorectal cancer or polyps,” said Char. “People don’t always want to talk about colonoscopy histories with their loved ones, but it is important information.”

Screening for other gastrointestinal cancers is not generally available, but certain symptoms can be an early indicator of the development of cancer. Symptoms such as blood in the stool, persistent acid reflux, heartburn, or unexplained abdominal or back pain all warrant a follow-up with a primary care doctor. In addition, a sudden onset of diabetes in adulthood is also an important potential warning sign of pancreatic cancer.

“It is important for people to be aware of symptoms and follow up with a doctor if they see or feel anything unusual,” said Char.

Treatment guidelines for early onset gastrointestinal cancers are the same as for average onset disease. However, the report notes that while younger patients are more likely to receive more aggressive treatment, this does not always provide benefits in terms of survival.

“More research is required to fully understand if there are biological differences between early and average onset disease, and if treatment differences are warranted,” said Char. “We need representation and diversity in the epidemiologic studies and other research that we conduct, so that we’re taking a holistic view of these diseases across a diverse population.”

“We need to be thinking not only about the risk factors for these diseases but also how to screen, diagnose, and treat young people with these cancers,” said Ng.

The team also reports that young patients with early onset gastrointestinal cancers have unique concerns, including worries about fertility and sexual dysfunction, financial strain, and psychosocial factors. The Young-Onset Colorectal Cancer Center at Dana-Farber Cancer Institute provides support that caters to the unique needs of young patients, including patient navigation, genetic counseling, fertility preservation, financial counseling, psychosocial support, and nutrition advice.

This news release was published Dana-Farber Cancer Institute on July 8, 2025.

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