Open Letter: In Support of Mandatory Nucleic Acid Synthesis Screening and Recordkeeping

As life sciences researchers, builders of AI and biotechnology, and experts with a wide range of views on how to approach AI policy, we call on legislators to make screening of orders for synthetic nucleic acids—and the equipment needed to make them—mandatory. 
The ability to order synthetic DNA online has accelerated vaccine development, powered basic research, and made it possible for small teams to access capabilities that used to be confined to major institutions. Since the publication of protocols to reconstruct viruses from strands of DNA more than two decades ago, it has also been recognized as a point in the biotechnology supply chain where a bad actor could cause outsized harm. Recognizing the vulnerability, synthesis companies formed the International Gene Synthesis Consortium in 2009 to develop and implement voluntary safeguards against misuse.

While the issue is not new, the pace of progress in artificial intelligence is. AI systems now outperform PhD-level virologists on questions about highly technical laboratory procedures in their own domains of expertise. The evidence about what this means for present-day biosecurity threats is genuinely mixed, but the trend is hard to dispute. AI systems are improving rapidly, and alongside incredible benefits to science and medicine, there is a real possibility that the knowledge barriers which have historically prevented bad actors from obtaining biological weapons will meaningfully erode.

Support for screening does not depend on any particular view of AI; the biosecurity case has been recognized by scientists and governments for decades. Screening is also one of the best understood and least disruptive biosecurity measures available. It asks providers of synthesized DNA and manufacturers of synthesis machines to check synthesis requests for sequences of concern and to verify customer legitimacy before shipping orders. Providers should also record synthesis orders and sequence data to support legitimate biosecurity investigations, so that any threat that might evade initial screening can be traced back to its source — including when individual sequences would not raise concern in isolation. Awareness of traceability itself deters misuse.

Many of the largest and most responsible providers in the industry already screen and record orders voluntarily because it is well understood that they have an important role to play in maintaining public trust in and mitigating potential misuse of this important technology.

For these reasons, the undersigned support mandatory nucleic acid synthesis screening, including recordkeeping, in the United States.

Given the pace at which the underlying technology is changing, we believe the need is urgent. Congress should act this session, and we applaud the legislative efforts currently underway. To ensure a consistent national standard rather than a patchwork of conflicting laws, states should also consider implementing requirements based on existing federal and industry guidelines.

This is a rare moment of agreement across stakeholders that are often at odds. We hope policymakers will meet it with decisive action.

Sincerely,

You can find the full list of signatories and the letter here. I am a media consultant working with the two organizations that are the primary organizers of the letter: the Institute for Progress (IFP) and the Foundation for American Innovation (FAI). The best email contact regarding the open letter is letter@screendna.org.

Carrie Hutcheson is senior director of the Glen Echo Group in Washington, DC.  

 

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Teachers’ Well-Being and Health in Germany: Representative Cross-Sectional Study

<strong>Background:</strong> Teachers play a fundamental role in the educational system and carry significant responsibilities. However, various occupational demands may compromise their health and well-being. At present, empirical data on the specific correlates of health and well-being among teachers in Germany remain limited, for example, regarding the relevance of health literacy. <strong>Objective:</strong> The primary aim of this study was to conduct a comprehensive assessment of the current health and well-being status among teachers. Specifically, the study aimed to quantify these factors according to the Positive Emotions, Engagement, Relationships, Meaning, and Accomplishments (PERMA) model as well as their general and mental health literacy. Secondary aims were to explore how health and well-being are associated with general and mental health literacy, as well as other personal and professional factors. <strong>Methods:</strong> This cross-sectional web-based survey was conducted in 2022 among teachers currently working in Germany. Participants were randomly sampled from all teachers in a general population panel (&gt;100,000 panelists recruited exclusively offline). In total, 61.6% (1005/1631) of the invited teachers participated (mean 49.99, SD 9.74 years). The final sample was weighted by gender, age, school type, and federal state. Health and well-being (PERMA Profiler questionnaire), general health literacy (European Health Literacy Survey Questionnaire, 16 items), mental health literacy (Mental Health Literacy Tool for the Workplace), sociodemographic (eg, gender and age), and professional information (school type, experience, and teaching load) were assessed. Bivariate (ANOVAs, <i>t</i> tests, and Pearson correlations) and multivariate (multiple regression) analyses were computed to analyze the associations between the health and well-being outcomes and the other factors. <strong>Results:</strong> The teachers reported intermediate to high well-being and health according to the PERMA model. In addition to significant bivariate associations, regression analysis for the well-being outcome (<i>F</i><sub>13, 977</sub>=10.66; <i>P</i>&lt;.001) revealed general (β=.23; <i>P</i>&lt;.001) and mental health literacy (β=.15; <i>P</i>&lt;.001) as significant positive predictors. In addition, teachers aged 40-49 years (β=–.12; <i>P</i>=.002) and 50-59 years (β=–.10; <i>P</i>=.03), as well as those with 10-19 years of experience (β=–.08; <i>P</i>=.04), reported significantly lower well-being than their younger/early-career peers. The regression model for the health outcome (<i>F</i><sub>13, 980</sub>=8.34; <i>P</i>&lt;.001) showed that general health literacy (β=.25; <i>P</i>&lt;.001), teaching at nonprimary schools (β=.10; <i>P</i>=.002), and a high teaching load (≥28 hours: β=.10; <i>P</i>=.02) were positively associated with the health outcome. Teaching experience of 10-19 years (β=–.09; <i>P</i>=.02) and older age (50-59 years: β=–.12; <i>P</i>=.02; ≥60 years: β=–.09; <i>P</i>=.046) predicted lower health scores. Other factors were not significant in the well-being and health regression models (all <i>P</i>&gt;.05). <strong>Conclusions:</strong> This study highlights the potential of health literacy as an intervention target for improving teachers’ health and well-being. To build on these findings, longitudinal and interventional studies are needed. <strong>Trial Registration:</strong>

STAT+: Drug companies, patient groups urge FDA to pause commissioner’s voucher program

WASHINGTON — Leaders at the Food and Drug Administration on Thursday listened to criticisms and recommendations for how to move forward with a speedy drug review program put in place by former FDA commissioner Marty Makary. 

The listening session, held on the FDA’s White Oak Campus, featured 17 speakers representing patient groups, drug companies, and academic organizations. Some had positive feedback, particularly those whose drugs have already been approved through the program. But most asked the agency to pause the program, and then bring it back through normal regulatory procedures that require public feedback. 

Makary launched the Commissioner’s National Priority Voucher program about a year ago, offering one- to two-month FDA reviews to companies that could prove their drugs “align with national priorities.” The priorities, which included addressing health crises and delivering innovative cures, were vague. Critics worried the process was vulnerable to political interference.

Continue to STAT+ to read the full story…

What RevMed’s pancreatic cancer drug meant for one patient

Why did oncologists give a standing ovation to a data presentation on Revolution Medicines’ pancreatic cancer drug, daraxonrasib? Why did biotech stocks perform so badly this week? And are concrete beaches better than normal beaches?

We discuss all that and more on this week’s episode of “The Readout LOUD,” STAT’s biotech podcast.

Read the rest…

Stipple Bio and Lonza Agree to Focus on Advancing Oncology ADC Therapies

Lonza and Stipple Bio signed a multi-target licensing agreement to support the development of next-generation precision oncology ADC therapies.

Officials at Stipple Bio say the company is leveraging its Pointillist Platform to identify tumor-specific cell surface epitopes, which can enable the development of high therapeutic index medicines designed to avoid on-target/off-tumor toxicity. Under the agreement, Stipple Bio will gain target-specific access to Lonza’s ADC technology platform to design potential first-in-class and best-in-class ADC products, including STP-100.

This collaboration combines Stipple Bio’s epitope discovery capabilities with Lonza’s GlycoConnect antibody conjugation technology, HydraSpace® polar spacer technology, and a toxSYN® linker payload. In addition, Lonza is eligible to receive upfront, clinical, regulatory and commercial milestone payments, plus royalties on net sales of resulting products. Lonza is responsible for manufacturing components that are related to its proprietary technologies, and Stipple Bio is responsible for the R&D, manufacturing, and commercialization of the ADCs.

“We value the opportunity to work with Stipple Bio to support their innovative epitope discovery approach with our advanced ADC technologies,” said Jan Vertommen, head of commercial development, advanced synthesis, Lonza. “By combining their science with Lonza’s established bioconjugation platforms and efficient, scalable manufacturing capabilities, we aim to help Stipple Bio progress more precise and effective ADC programs with confidence and speed.”

“ADCs have become a core pillar of cancer treatment, and as the field advances, increasingly sophisticated design is translating into stronger efficacy and reduced off-target effects,” added Jeff Landau, CEO, Stipple Bio. “We are pleased to be partnering with Lonza and believe that their clinically validated platform will be instrumental in enabling us to translate that design sophistication into effective and better tolerated therapies.”

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STAT+: Otsuka kidney drug slowed loss of function, but less than expected, in late-stage trial

Otsuka’s Voyxact slowed the loss of kidney function after one year in patients with a chronic autoimmune kidney disease, but the benefit was less than expected and left room for competing treatments to perform better. 

In a Phase 3 study, patients with IgA nephropathy, or IgAN, who received injections of Voyxact saw their kidneys lose function at an annualized rate of 3 points over one year compared to an annualized function loss of 7.6 points over one year for patients receiving a placebo, the Japanese drugmaker reported Thursday. 

Kidney function was assessed with a lab test, called eGFR, that measures how well kidneys filter waste from the blood. 

Continue to STAT+ to read the full story…

Experimental Adjuvant Could Strengthen Mucosal Immunity with Injectable Polio Vaccines

The injectable form of the polio vaccine has proven effective at preventing illness but it does not block the transmission of the virus as well as the oral version of the vaccine. That is because the virus is usually transmitted through contaminated food or water and is first exposed to the GI tract, where the oral vaccine induces a mucosal immune response. To date, several countries no longer use the oral vaccine because there is a small risk of infection. It is also possible for people who receive the injected polio vaccine to spread the virus even though they are asymptomatic. 

Now according to data from an Massachusetts Institute of Technology-led study, it may be possible to modify the injectable vaccine so that it can also promote a mucosal immune response. This way, the vaccine could support polio eradication efforts without the risks of the oral polio vaccine. Details are published in a new Science Advances paper titled “Am80-Lipid nanoparticles serve as an enteric mucosal adjuvant 3 following parenteral immunization with inactivated polio vaccine.”

In comments that shed some light on the thinking behind the work, Ana Jaklenec, PhD, a principal investigator in MIT’s Koch Institute for Integrative Cancer Research, stated that while “people who are vaccinated with the injectable vaccine are not getting sick” they may be helping spread the highly contagious virus. “Mucosal immunity could help lower that shedding and ideally eliminate it,” she said. 

Her team’s version of the vaccine comprises an injectable, inactivated polio vaccine delivered with a nanoparticle-based adjuvant that helps steer immune cells to the mucosal lining of the intestine. Digging into the details, Jaklenec and her team worked with a group at Harvard Medical School who have shown previously that using a derivative of vitamin A as a vaccine adjuvant can help stimulate immune cells to go into the GI tract. 

Though the adjuvant, known as Am80, generates a strong response, one challenge is that it needs to be injected for several days in a row, which is not feasible for most vaccine campaigns. To eliminate the need for repeated vaccinations, the scientists used a lipid nanoparticle (LNP) as a delivery vehicle that releases the adjuvant slowly over several days.

Armed with the updated vaccine, the scientists moved on to testing it in rats. For their tests, the scientists injected the standard inactivated polio vaccine along with a separate injection of Am80 encapsulated in LNPs. They also delivered boosters to the rats at four and eight weeks. 

Following injection, LNPs accumulate in the lymph nodes where they interact with B and T cells that are also exposed to the polio vaccine. The interaction stimulates the cells to produce two surface proteins that direct them to the GI tract. Additionally, the B cells produce IgA antibodies, which protect body surfaces from infection by coating the mucosal membranes. Lastly the rats produce IgG antibodies in the bloodstream, which are similar to the antibodies produced in response to the standard injected polio vaccine. 

Overall, in the rats, they found that administering the vaccine and adjuvant produced a two-fold increase in the type of antibodies needed for mucosal immunity compared to the inactivated vaccine alone. Essentially, “by adding Am80 to lipid nanoparticle as an adjuvant, we are combining the safety of IPV with an adjuvant that can produce the mucosal immunity that normally you can only get with OPV,” said Behnaz Eshaghi, PhD, a postdoctoral student at MIT and lead author of the paper. 

For their next steps, the scientists plan to test the improved vaccine in other large animal models where they will inject the vaccine and adjuvant mixed together. More broadly, Am80 and similar adjuvants could help scientists design improved vaccines for other pathogens that infect the GI tract or for diseases that infect the lungs or reproductive tract. 

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Post-Stroke Arm Immobility Improved with Spinal Cord Stimulation

Stroke is the leading cause of arm and hand hemiparesis, weakness or paralysis on one side of the body, with about 80% of stroke patients experiencing at least partial weakness. Many stroke survivors rank improving arm function as a high priority for recovery, but effective treatments are not currently available.

Researchers at the University of Pittsburgh have just published the results of a pilot clinical trial to address this unmet need. Their work, which uses cervical spinal cord stimulation (SCS) to enhance arm and hand function was published in Nature Medicine.

“From a clinical perspective, even modest improvements in arm strength or control can make a meaningful difference in daily life of stroke survivors,” said study co-author George Wittenberg, MD, PhD, professor at the University of Pittsburgh School of Medicine.

This small pilot study included seven patients with varying levels of muscle hemiparesis caused by stroke. All patients presented with profound motor defects, with Fugl-Meyer Assessment (FMA) scores ranging from 15 to 35 (for context, the higher the score, the less impairment, with scores below 50 indicating severe impairment and scores over 100 indicating minimal to no impairment). Each patient was implanted with two leads implanted unilaterally in the cervical spinal cord and underwent SCS stimulation and worked on motor activity under researcher guidance over a four-week period.

During SCS testing, all patients experienced improvement in motor function with an average increase of 32% in strength and increase of 5.6 FMA points on average. After approximately 8.6 hours of motor activity (5.5 hours of which were with the SCS on), the FMA scores improved on average by 6.6 FMA points.

Researchers adjust spinal cord stimulation settings in real time to test their effects on arm and hand movement during stroke rehabilitation. [UPMC and University of Pittsburgh Health Sciences]

“This approach is designed to rapidly help people move their arms better, even years after a stroke,” said co-senior author Marco Capogrosso, PhD, assistant professor at the University of Pittsburgh and director of the spinal cord stimulation laboratory at Rehab Neural Engineering Labs in the UPMC Rehabilitation Institute.

“The stimulation works mostly as an assistive technology—when it’s on, people can move better,” Capogrosso continued. “By stimulating the spinal cord, we can immediately allow residual connections between the brain and the spinal cord to work more efficiently, enabling better movement.”

“Some of the improvements we measure may look small from the outside, but many stroke survivors are just on the verge of being able to do something important,” said Wittenberg. “Even a small change in motor function can be very significant if it helps someone button a shirt, open their hand or return to an activity they care about.”

While the patients in the study experienced immediate improvements to motor function, maintained improvement depended on continued use of SCS. Additional assessments showed motor function declined without continued stimulation, suggesting that the future use of SCS may not be with short-term use in rehabilitation but rather an assistive neuroprosthetic technology.

“This study represents the conclusion of our initial feasibility phase and an important step toward real-world clinical application,” Capogrosso said.

Based on the positive results from this pilot program, the researchers plan to expand the patient poll for a larger clinical trial to better understand the consequences of long-term SCS use, with and without physical therapy.

“Our goal is to develop a technology that could eventually be used in everyday life, not just in the clinic,” Capograsso concluded. “These results give us confidence that spinal cord stimulation could become a practical, implantable option for helping stroke survivors use their arms when it matters most.”

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Infant Brain Development Sheds Light on Parkinson’s Link with Autism

Changes in the brains of babies shortly after birth could help explain why people go on to develop Parkinson’s disease (PD) and why this is particularly common in people with autism spectrum disorder (ASD).

The findings, in Science Advances, suggest a reason why humans are vulnerable to neurodegenerative diseases in a way that is not seen among other primates.

Researchers were surprised to find increased expression in genes associated with PD among humans that was not found in chimps or rhesus monkeys.

Human changes in regulatory DNA operated across two cell lineages, one linked with autism and the other with PD.

“Patients with ASD are also more likely to develop PD, a link that is currently not understood,” commented the researchers, led by Menno Creyghton, PhD, from Erasmus University Medical Center in the Netherlands.

“Our analysis linking the two diseases through a common network could provide insight into common biology between the two diseases.”

Human brains have several differences to those of primates, including a larger volume, more projections between outermost areas, and greater complexity of neurons in the upper layer.

The researchers note that, soon after birth, babies experience protracted brain development that coincides with periods of extensive synaptic modeling.

To investigate differences with our close evolutionary relatives, they conducted a single-cell transcriptomic and epigenomic analysis of human, rhesus macaque, and chimpanzee brain tissue during early postnatal development.

Through this, the team identified human infant–specific programs and cell states that were not observed in adults and correlated these early life processes with susceptibility to PD in aged neurons.

Specifically, Creyghton and co-workers identified human gene expression changes in immature oligodendrocytes enriched in both ASD risk genes and gene expression losses in patients with ASD.

There were also gene expression gains in human babies enriched in PD risk genes for and among genes dysregulated in PD patients.

Both transcriptional programs were part of a core network that contained human-specific sequence changes in regulatory DNA. This lacked cell lineage specificity, operating in both the oligodendrocyte and neuronal lineages, with different downstream targets for each.

In the oligodendrocyte lineage, the downstream target genes were overrepresented in autism risk genes whereas in the neural lineage, PD risk genes were enriched.

“It is therefore possible that these pathologies could be maintained in the human lineage by complex antagonistic interactions across developmental stages,” the authors speculated.

They noted the “unexpected” correlation between human evolution and Parkinson’s disease.

“It has been suggested that humans are exceptionally vulnerable to neurodegenerative diseases including PD as similar disease pathology has not clearly been observed in other primate species,” the team pointed out.

“We show that the human infant–specific expression changes that are overrepresented in PD-deregulated genes are enriched in synaptic developmental genes.

“Imbalances in synaptic function can strongly affect neural vulnerabilities, especially in larger projection neurons. As such, pathological deregulation of such a program may play a role in PD susceptibility.”

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Alzheimer’s Genetic Risk Loci: 16 New Candidates

A comprehensive international genetics study found several new genetic risk factors for Alzheimer’s disease and related dementias, providing one of the clearest pictures of the biological pathways that cause the devastating neurodegenerative disorder.

Published in the journal Nature Genetics, the study combined data from 978,514 people of European ancestry, including over 128,681 individuals with Alzheimer’s disease and related dementias (ADRD). The researchers found 91 regions of the genome linked to dementia risk, including 16 new loci that had not been linked to Alzheimer’s in European populations.

The project brought together several major research consortia, including the European Alzheimer and Dementia Biobank, the International Genomics of Alzheimer’s Project, and the Psychiatric Genomics Consortium. By pooling results from 52 studies, scientists created one of the largest and most comprehensive genome-wide association analyses ever conducted for Alzheimer’s research.

Although aging is the strongest risk factor for Alzheimer’s disease, which affects tens of millions of people worldwide, genetics plays a major role in disease development. The APOE ε4 gene is known to strongly increase Alzheimer’s risk, but scientists believe many additional genes contribute smaller effects that together shape vulnerability.

The new study significantly expands that genetic map. Newly identified risk regions include genes involved in immune signaling, lipid metabolism, and cellular waste disposal—processes already suspected to contribute to the buildup of amyloid plaques and tau tangles, the hallmark pathologies of Alzheimer’s disease.

Several of the newly discovered loci, including SRC, PTPRC, MGAT5, and DOCK4, point toward the importance of microglia, the brain’s immune cells. Previous studies have suggested that dysfunctional immune responses may accelerate neurodegeneration by impairing the brain’s ability to clear toxic proteins.

Researchers also found evidence that many Alzheimer’s-associated genes are highly active in microglia across multiple brain regions, reinforcing the idea that inflammation and immune regulation are central to disease progression.

To distinguish true Alzheimer’s signals from broader dementia-related effects, the team performed additional analyses excluding “proxy” cases—individuals reporting a parent or sibling with dementia—and excluding large biobank datasets based primarily on medical coding. Even under these stricter conditions, 56 of the identified loci remained strongly associated with clinically diagnosed Alzheimer’s disease, suggesting the findings are robust.

Beyond identifying genes, the researchers tested how combined genetic risk influences brain pathology. They created polygenic risk scores using Alzheimer’s-associated variants other than APOE and examined their relationship to postmortem brain changes.

Individuals in the highest 10% of genetic risk had roughly double the likelihood of severe tau tangles and amyloid plaque buildup compared with people in the middle-risk group. Conversely, individuals in the lowest 10% had substantially reduced risk.

Importantly, the genetic scores were more strongly linked to classic Alzheimer’s pathology than to other forms of brain damage such as strokes or vascular disease. This suggests that many of the identified variants specifically contribute to Alzheimer’s biological mechanisms rather than dementia in general.

Despite the scale of the study, researchers caution that genetics alone cannot fully predict who will develop Alzheimer’s. The polygenic scores explained only a modest portion of disease variability, highlighting the continued importance of environmental and lifestyle factors.

Still, scientists say the findings could help accelerate the search for new drug targets and improve future risk prediction tools. The study also emphasizes the necessity of larger and more diverse datasets, as the current analysis focused primarily on individuals of European ancestry.

Future work will examine how rare genetic variants and structural changes in DNA contribute to Alzheimer’s biology, potentially paving the way to precision medicine and earlier intervention.

 

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