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Drug discovery Is changing. Drug development must change too

💬 Artificial intelligence and big data are flooding discovery pipelines with high-potential drug candidates, but this rapid innovation has created a new challenge. Simply put, our capability to design miracle molecules is vastly outstripping our technology to mass-manufacture them safely for the global public. Moving drug making from the scale of lab flasks to commercial bioreactors introduces non-linear biological and engineering shifts that can undermine tasks like purification.

⚡In this New Scientist CoLab podcast, experts from global life sciences leader Cytiva explain the hidden, high-stakes science of purification that is required to close the gap between drug discovery and the pharmacy shelf.

Gene activity in blood fluctuates more than expected—and that has consequences for medicine

Take a blood sample from someone in the dead of winter. Take another in midsummer. Same person, same laboratory. And yet, at the level of gene activity, the molecular picture can look surprisingly different. This is not an anomaly. This, a new Nature Communications study argues, is simply how human biology works, and it has significant implications for the way biomarkers have traditionally been studied.

Researchers from Kiel University’s Excellence Cluster PMI, KU Leuven and the German Center for Neurodegenerative Diseases (DZNE) in Bonn tracked 333 volunteers in Flanders over six months, drawing blood three times and measuring the activity of roughly 14,000 genes on each occasion.

What they found suggests that an important source of biological variation has been underappreciated in many clinical studies: in 85% of all genes, the variation within a single person over time is larger than the variation between different people. In other words, for most genes, the largest differences are observed between two time points in the same individual rather than between different individuals.

Materials surrounding a fusion reaction can dramatically increase how often it occurs

Fusion at high temperatures powers the sun and, if harnessed, could provide a potential source of energy here on Earth. But controlling fusion reactions has other benefits. The process also generates subatomic particles called neutrons that are used in a range of applications spanning medicine, research and national security.

Scientists at the University of California, Davis, and the Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab) have found that the materials surrounding a fusion reaction can dramatically increase how often it occurs, particularly at low energies where fusion is rare. Their study is published in Nature Communications. The study’s first author is Micah Karahadian, a doctoral candidate in Munday’s lab at UC Davis.

Their approach establishes a way to study and engineer nuclear reactions within solid materials, opening a new field of “materials-driven fusion.” Instead of designing materials just to survive the harsh conditions of fusion, researchers might be able to design materials that boost the reaction under specific conditions, similar to the way catalysts speed up chemical processes.

Programmable platform enables on-demand design of plant immune receptors against crop pathogens

Crop production faces threats from plant pathogens. Traditional disease-resistance breeding relies heavily on natural plant resistance genes that encode immune receptors adapted to particular pathogens. However, rapidly evolving pathogens frequently overcome these natural defenses, and the limited diversity of naturally occurring immune receptors makes it difficult to develop crops with durable resistance.

Now, a team led by Professor Gao Caixia at the Institute of Genetics and Developmental Biology (IGDB) of the Chinese Academy of Sciences has developed a programmable platform for the on-demand design of synthetic plant immune receptors (SPIRs) that recognize proteins from diverse plant pathogens.

The study was published online in Science on July 23.

Blurred genome boundaries emerge as a new layer of Alzheimer’s biology

Researchers from Carnegie Mellon University’s School of Computer Science, the University of Pittsburgh School of Medicine and the University of Washington have shed new light on Alzheimer’s disease that could point to new directions for treatment.

In a paper published in Science, researchers from SCS’s Ray and Stephanie Lane Computational Biology Department, Pitt’s Department of Neurobiology and collaborating institutions show that 3D genome architecture is organized differently in certain brain cells from people with Alzheimer’s disease, uncovering a previously underexplored layer of the disease’s biology.

The research team linked genome folding to gene activity and brain tissue organization in Alzheimer’s disease. The team did this with single-cell technology, spatial mapping of brain tissue and a new deep-learning model.

The perfect pesticide?

A native of the Rocky Mountains, the beetle now occurs across the Northern Hemisphere, causing more than half a billion dollars of crop losses each year. It’s a master of resistance, making it hard to control. The pest was an early driver of research into chemical pesticides starting in the 1930s. Ever since, it has evolved immunity to one compound after another—now more than 50 pesticides, representing all major types of active ingredients.

“They were chewing through treated plants like it was nothing,” Andrei Alyokhin, an entomologist at the University of Maine, says of the moment, in 2001, when farmers in Maine noticed that a still-new class of pesticides, neonicotinoids, were no longer controlling the beetle. Finding additional tools has been “increasingly difficult,” he adds.

This year, however, U.S. farmers will have a new weapon against the pest, one that works in an entirely different way from traditional pesticides and that proponents say should be safer for people and the environment. Based on a mechanism called RNA interference (RNAi), the spray targets a vital gene in the Colorado potato beetle. The gene target is unique to the pest and its close relatives, which should prevent damage to pollinators and other species. “You can 
 hit the insect you want to kill with precision,” says Subba Reddy Palli, an entomologist at the University of Kentucky who published a review last year in Frontiers in Insect Science describing the development of RNA-based pesticides. “You cannot get anything better than this.”

Artery-on-a-chip helps predict stroke risk

Predicting an individual’s risk of ischemic stroke is difficult because thrombosis embolization—the process of a blood clot detaching from the area where it formed, traveling and then sticking in another blood vessel—is based on factors unique to each person.

In a study published in Cell Biomaterials, researchers developed a tool to address this challenge: an artery-on-a-chip platform that can replicate a patient’s specific vascular structure and blood flow dynamics, called a “physical twin.”

“This idea was born out of a critical clinical gap,” says author Lining Arnold Ju of the University of Sydney in Australia. “We know that even patients at ‘low risk’ can suffer from severe or fatal strokes. We wanted to find a better way to predict this risk.”