Science

The ingredient, diquat, is widely employed in the US as a weedkiller in vineyards and orchards, and is increasingly sprayed elsewhere as the use of controversial herbicide substances such as glyphosate and paraquat drops in the US.

But the new piece of data suggests diquat is more toxic than glyphosate, and the substance is banned over its risks in the UK, EU, China and many other countries. Still, the EPA has resisted calls for a ban, and Roundup formulas with the ingredient hit the shelves last year. Foam washes up from a body of water onto sandy ground with scrubby plants. ‘We thought we’d got the numbers wrong’: how a pristine lake came to have the highest levels of ‘forever chemicals’ on record Read more

“From a human health perspective, this stuff is quite a bit nastier than glyphosate so we’re seeing a regrettable substitution, and the ineffective regulatory structure is allowing it,” said Nathan Donley, science director with the Center For Biological Diversity, which advocates for stricter pesticide regulations but was not involved in the new research. “Regrettable substitution” is a scientific term used to describe the replacement of a toxic substance in a consumer product with an ingredient that is also toxic.

Diquat is also thought to be a neurotoxin, carcinogen and linked to Parkinson’s disease. An October analysis of EPA data by the Friends of the Earth non-profit found it is about 200 times more toxic than glyphosate in terms of chronic exposure.

Bayer, which makes Roundup, faced nearly 175,000 lawsuits alleging that the product’s users were harmed by the product. Bayer, which bought Monsanto in 2018, reformulated Roundup after the International Agency for Research on Cancer classified glyphosate as a possible carcinogen.

The new review of scientific literature in part focuses on the multiple ways in which diquat damages organs and gut bacteria, including by reducing the level of proteins that are key pieces of the gut lining. The weakening can allow toxins and pathogens to move from the stomach into the bloodstream, and trigger inflammation in the intestines and throughout the body. Meanwhile, diquat can inhibit the production of beneficial bacteria that maintain the gut lining.

Damage to the lining also inhibits the absorption of nutrients and energy metabolism, the authors said.

The research further scrutinizes how the substance harms the kidneys, lungs and liver. Diquat “causes irreversible structural and functional damage to the kidneys” because it can destroy kidney cells’ membranes and interfere with cell signals. The effects on the liver are similar, and the ingredient causes the production of proteins that inflame the organ.

Meanwhile, it seems to attack the lungs by triggering inflammation that damages the organ’s tissue. More broadly, the inflammation caused by diquat may cause multiple organ dysfunction syndrome, a scenario in which organ systems begin to fail.

The authors note that many of the studies are on rodents and more research on low, long-term exposure is needed. Bayer did not immediately respond to a request for comment.

Despite the risks amid a rise in diquat’s use, the EPA is not reviewing the chemical, and even non-profits that push for tighter pesticide regulations have largely focused their attention elsewhere.

Donley said that was in part because US pesticide regulations are so weak that advocates are tied up with battles over ingredients like glyphosate, paraquat and chlorpyrifos – substances that are banned elsewhere but still widely used here. Diquat is “overshadowed” by those ingredients.

“Other countries have banned diquat, but in the US we’re still fighting the fights that Europe won 20 years ago,” Donley said. “It hasn’t gotten to the radar of most groups and that really says a lot about the sad and sorry state of pesticides in the US.”

Some advocates have accused the EPA of being captured by industry, and Donley said US pesticide laws were so weak that it was difficult for the agency to ban ingredients, even if the will exists. For example, the agency banned chlorpyrifos in 2022, but a court overturned the decision after industry sued.

Moreover, the EPA’s pesticides office seems to have a philosophy that states that toxic pesticides are a “necessary evil”, Donley said.

“When you approach an issue from that lens there’s only so much you will do,” he said.

Scientists in various fields have tried for years to figure out how paternal-only DNA could sustain a mammal through all stages of life.

A small team of researchers has reported a striking achievement: they succeeded in raising a mouse that came from two male parents, and it grew into a healthy adult. Their work unveils a set of genetic changes that overcomes the imprinting barriers that typically block such development.

Scientists in various fields have tried for years to figure out how paternal-only DNA could sustain a mammal through all stages of life.

Biological imprinting is an inherited pattern of gene expression. It involves certain genes getting turned on or off depending on whether they come from the father or the mother.

Researchers found that if you adjust a selection of these imprinting genes, you can open the door for unique reproductive feats, such as an embryo that starts with only paternal cells.

“This work will help to address a number of limitations in stem cell and regenerative medicine research,” explains Wei Li of the Chinese Academy of Sciences in Beijing.

In this case, the scientists homed in on key sections of DNA that are known to control fetal growth and viability.

What this means for biology

When a mouse embryo is formed in the usual way, paternal and maternal DNA come together. That combination produces a precise balance of imprinted genes.

In paternal-only embryos, certain growth-related genes can become overstimulated, but the team was able to selectively modify them so these embryos could mature.

“These findings provide strong evidence that imprinting abnormalities are the main barrier to mammalian unisexual reproduction,” said Qi Zhou, co-lead of this study.

By re-engineering the problematic gene regions, the researchers made it possible for two sets of male chromosomes to support a developing mouse. Therapeutic ideas

A number of genetic and metabolic disorders in humans stem from errors in imprinting. Scientists have asked whether strategies used here might be adapted to correct imprinting problems that cause diseases in people.

One potential target is KCNK9, which has been linked to Birk-Barel syndrome. Precise gene editing of such imprinting sites could help in the design of improved treatments for these rare disorders.

In practice, these ideas may take time to progress. Mouse models are often a first step in studying how imprinting influences development.

The more scientists understand about restoring the right imprinting patterns, the closer they might come to tackling certain medical conditions. Gene imprinting implications

The modified imprinting genes not only allowed bi-paternal mice to survive to adulthood, they also improved the efficiency of stem cells used in the process.

The researchers reported that these engineered embryonic stem cells were about twice as likely to develop into full-term pups compared to unmodified cells.

This improved developmental stability could change how scientists approach cloning. Currently, cloned animals often suffer from low survival rates and severe abnormalities, in part due to faulty imprinting.

Fixing imprinting errors ahead of time might make future cloning methods more reliable, especially in complex mammals like primates. Ethical considerations

Questions often arise about how these approaches could extend to humans.

According to guidelines from the International Society for Stem Cell Research (ISSCR), heritable genome editing is not currently allowed for human reproductive purposes because it is considered unsafe.

Researchers continue to examine these practices in animal models before even considering steps that approach human application. Investigators involved in this work remain cautious.

While a mouse with two fathers has captured headlines, translating similar methods to people is a bigger leap.

The focus remains on unraveling how imprinted genes function, and how targeted interventions might fix imprinting-related diseases down the road. Next questions

There is still room to explore how best to refine these genetic strategies to improve survival rates and lessen the chance of complications.

Specialists are also looking at future animal models to see if placental differences, organ development, or immune responses undergo subtle changes when imprinting is modified.

Some foresee that data gleaned from these methods will shape the next generation of gene-editing research.

Ongoing studies point to a need for caution. Issues like longevity, fertility, and normal physiology require much deeper evaluation.

Still, scientists see value in applying these insights to refine cloning and enhance studies of embryonic stem cells. Even partial solutions could inform safer protocols for regenerating cells and tissues in healthcare settings.

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This breakthrough was led by Wei Li of the Chinese Academy of Sciences in Beijing and Qi Zhou of the same institution, with further input from collaborators at Sun Yat-sen University.

The study is published in Cell Stem Cell.