Science
Could a single synthetic molecule outsmart a variety of drug-resistant bacteria?
An estimated 2.8 million people in the U.S. contract infections each year from bacteria resistant to antibiotics, according to the U.S. Centers for Disease Control. More than 35,000 of them die.
Despite the mounting toll — and the prospect of an eventual surge in superbug fatalities — the development of new antibiotics has failed to keep pace with the threat. A new medicine capable of combating Gram-negative bacteria, a particularly hardy type of bug with inner and outer membranes that antibiotics struggle to cross, hasn’t hit the market in 50 years.
So when a new substance appears on the scene with a decent chance of eventually becoming one of these desperately-needed drugs, scientists say it’s a big deal.
Researchers at Harvard and the University of Illinois at Chicago have created a new molecule that effectively vanquished multiple types of bacteria when tested in animals. The organisms on its hit list included strains of Staphylococcus aureus, Escherichia coli and other pathogens that have become resistant to most antibiotics currently available.
The new molecule, dubbed cresomycin, was described Thursday in the journal Science.
Cresomycin is not yet a drug, nor is it close to being ready for clinical trials in humans. But it represents a promising enough step toward new treatments that a nonprofit dedicated to fighting superbugs gave its Harvard creator $1.2 million this week to develop cresomycin and similar substances into new oral antibiotics.
“I’ve never been more optimistic or excited about a project,” said Andrew Myers, the Harvard University chemist whose lab developed the molecule.
Cresomycin belongs to a class of antibiotics known as enhanced lincosamides. It works by targeting a bacterium’s ribosome, the tiny protein factory tucked in every living cell.
“Ribosomes can be viewed as a molecular 3-D printer,” said Yury Polikanov, a structural biologist at the University of Illinois at Chicago and a co-author of the paper.
Just as those machines take plastic molecules and use them to construct objects of any shape, ribosomes take genetic information from RNA and use it to crank out proteins.
Since proteins are essential to virtually all cellular activity, ribosomes are vital to bacteria. That’s why many antibiotics are designed to target them.
But bacteria are always evolving — and embracing new adaptations that help them thwart our attempts to kill them. In some cases, bacteria do this by inserting a tiny chemical dab known as a methyl group into its ribosome. When an antibiotic attempts to bind to the ribosome, that methyl group repels it.
The methyl group acts like a tiny thumbtack set out on the seat the antibiotic was hoping to take, Polikanov said.
“Not very comfortable to sit when a needle is poking you,” he said.
But unlike previous antibiotics, cresomycin binds so tightly to the ribosome that it essentially negates the effect of the methyl group.
Returning to the thumbtack analogy, Polikanov said the molecule sits on its ribosome seat with such force that it drives the tack into the chair. The ribosome’s best defense is neutralized, allowing cresomycin to get on with its bacteria-killing work.
In test tubes, cresomycin proved much more effective than currently available antibiotics at inhibiting the growth of several types of bacteria. These included a nasty bug called carbapenem-resistant Acinetobacter baumannii that tends to show up in hospitals, E. coli and Neisseria gonorrhoeae, the bacteria that causes gonorrhea.
Researchers then took 20 mice and deliberately infected them with methicillin-resistant S. aureus, better known as MRSA. Half the mice were given four injections of cresomycin over the course of a day, and the other half received injections without the active ingredient.
All but one of the mice who didn’t get treatment were dead two days later. In contrast, all 10 of the mice who received cresomycin were still alive seven days after treatment.
In the Science paper, the authors were quick to note that cresomycin is not yet ready for clinical trials in humans.
The Harvard lab manufactured more than 60 molecules in its quest for one as effective as cresomycin, and that presents just a tiny fraction of the “exponentially greater numbers” of possible variations they could make, Myers said. As the researchers continue their work, they may find an even better candidate for eventual drug development.
Yet even at this stage, cresomycin represents an exciting possibility, according to experts who weren’t involved in the work.
“Probably about one in 1,000 projects make it to the level where he’s got it,” said Richard Alm, chief scientific officer at the Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator, or CARB-X, which gave Myers the $1.2-million grant. Of potential drugs that make it to the stage of development that cresomycin has reached, Alm estimated that one in every 30 or 40 ultimately has enough positive data to win approval from the U.S. Food and Drug Administration.
CARB-X is a global nonprofit dedicated to speeding up development of new antibiotics. It has made nearly 100 grants so far to companies or academic institutions working to treat, prevent or diagnose antibiotic-resistant infections. Headquartered at Boston University, the accelerator is funded by the governments of the U.S., the United Kingdom, Canada and Germany, as well as the Bill and Melinda Gates Foundation and the Novo Nordisk Foundation.
Development of antibiotics has stalled in part because they aren’t as potentially lucrative as other drugs, Alm said. They aren’t meant to be taken over the long term like medications for chronic conditions like diabetes or high blood pressure. And doctors want to use the most potent ones as rarely as possible, to give bacteria fewer chances to develop resistance to them.
All of that makes it a lot harder to recoup the costs of producing an effective antibiotic, Alm said. Efforts like CARB-X are an attempt to keep the pipeline from drying up.
“If your house is burning, you don’t have time to buy a fire truck, hire firemen and train them to come and put your fire out. You need them ready to go,” Alm said. “That’s the same with antibiotics. If you go into hospital and you get a superbug, you need an antibiotic that is there on the shelf.”
Science
California’s last nuclear plant clears major hurdle to power on
California environmental regulators on Thursday struck a landmark deal with Pacific Gas & Electric to extend the life of the state’s last remaining nuclear power plant in exchange for thousands of acres of new land conservation in San Luis Obispo County.
PG&E’s agreement with the California Coastal Commission is a key hurdle for the Diablo Canyon nuclear plant to remain online until at least 2030. The plant was slated to close this year, largely due to concerns over seismic safety, but state officials pushed to delay it — saying the plant remains essential for the reliable operation of California’s electrical grid. Diablo Canyon provides nearly 9% of the electricity generated in the state, making it the state’s single largest source.
The Coastal Commission voted 9-3 to approve the plan, settling the fate of some 12,000 acres that surround the power plant as a means of compensation for environmental harm caused by its continued operation.
Nuclear power does not emit greenhouse gases. But Diablo Canyon uses an estimated 2.5 billion gallons of ocean water each day to absorb heat in a process known as “once-through cooling,” which kills an estimated two billion or more marine organisms each year.
Some stakeholders in the region celebrated the conservation deal, while others were disappointed by the decision to trade land for marine impacts — including a Native tribe that had hoped the land would be returned to them. Diablo Canyon sits along one of the most rugged and ecologically rich stretches of the California coast.
Under the agreement, PG&E will immediately transfer a 4,500-acre parcel on the north side of the property known as the “North Ranch” into a conservation easement and pursue transfer of its ownership to a public agency such as the California Department of Parks and Recreation, a nonprofit land conservation organization or tribe. A purchase by State Parks would result in a more than 50% expansion of the existing Montaña de Oro State Park.
PG&E will also offer a 2,200-acre parcel on the southern part of the property known as “Wild Cherry Canyon” for purchase by a government agency, nonprofit land conservation organization or tribe. In addition, the utility will provide $10 million to plan and manage roughly 25 miles of new public access trails across the entire property.
“It’s going to be something that changes lives on the Central Coast in perpetuity,” Commissioner Christopher Lopez said at the meeting. “This matters to generations that have yet to exist on this planet … this is going to be a place that so many people mark in their minds as a place that transforms their lives as they visit and recreate and love it in a way most of us can’t even imagine today.”
Critically, the plan could see Diablo Canyon remain operational much longer than the five years dictated by Thursday’s agreement. While the state Legislature only authorized the plant to operate through 2030, PG&E’s federal license renewal would cover 20 years of operations, potentially keeping it online until 2045.
Should that happen, the utility would need to make additional land concessions, including expanding an existing conservation area on the southern part of the property known as the “South Ranch” to 2,500 acres. The plan also includes rights of first refusal for a government agency or a land conservation group to purchase the entirety of the South Ranch, 5,000 acres, along with Wild Cherry Canyon — after 2030.
Pelicans along the concrete breakwater at Pacific Gas and Electric’s Diablo Canyon Power Plant
(Brian van der Brug/Los Angeles Times)
Many stakeholders were frustrated by the carve-out for the South Ranch, but still saw the agreement as an overall victory for Californians.
“It is a once in a lifetime opportunity,” Sen. John Laird (D-Santa Cruz) said in a phone call ahead of Thursday’s vote. “I have not been out there where it has not been breathtakingly beautiful, where it is not this incredible, unique location, where you’re not seeing, for much of it, a human structure anywhere. It is just one of those last unique opportunities to protect very special land near the California coast.”
Others, however, described the deal as disappointing and inadequate.
That includes many of the region’s Native Americans who said they felt sidelined by the agreement. The deal does not preclude tribal groups from purchasing the land in the future, but it doesn’t guarantee that or give them priority.
The yak titʸu titʸu yak tiłhini Northern Chumash Tribe of San Luis Obispo County and Region, which met with the Coastal Commission several times in the lead-up to Thursday’s vote, had hoped to see the land returned to them.
Scott Lanthrop is a member of the tribe’s board and has worked on the issue for several years.
“The sad part is our group is not being recognized as the ultimate conservationist,” he told The Times. “Any normal person, if you ask the question, would you rather have a tribal group that is totally connected to earth and wind and water, or would you like to have some state agency or gigantic NGO manage this land, I think the answer would be, ‘Hey, you probably should give it back to the tribe.’”
Tribe chair Mona Tucker said she fears that free public access to the land could end up harming it instead of helping it, as the Coastal Commission intends.
“In my mind, I’m not understanding how taking the land … is mitigation for marine life,” Tucker said. “It doesn’t change anything as far as impacts to the water. It changes a lot as far as impacts to the land.”
Montaña de Oro State Park.
(Christopher Reynolds / Los Angeles Times)
The deal has been complicated by jurisdictional questions, including who can determine what happens to the land. While PG&E owns the North Ranch parcel that could be transferred to State Parks, the South Ranch and Wild Cherry Canyon are owned by its subsidiary, Eureka Energy Company.
What’s more, the California Public Utilities Commission, which regulates utilities such as PG&E, has a Tribal Land Transfer Policy that calls for investor-owned power companies to transfer land they no longer want to Native American tribes.
In the case of Diablo Canyon, the Coastal Commission became the decision maker because it has the job of compensating for environmental harm from the facility’s continued operation. Since the commission determined Diablo’s use of ocean water can’t be avoided, it looked at land conservation as the next best method.
This “out-of-kind” trade-off is a rare, but not unheard of way of making up for the loss of marine life. It’s an approach that is “feasible and more likely to succeed” than several other methods considered, according to the commission’s staff report.
“This plan supports the continued operation of a major source of reliable electricity for California, and is in alignment with our state’s clean energy goals and focus on coastal protection,” Paula Gerfen, Diablo Canyon’s senior vice president and chief nuclear officer, said in a statement.
But Assemblymember Dawn Addis (D-Morro Bay) said the deal was “not the best we can do” — particularly because the fate of the South Ranch now depends on the plant staying in operation beyond 2030.
“I believe the time really is now for the immediate full conservation of the 12,000 [acres], and to bring accountability and trust back for the voters of San Luis Obispo County,” Addis said during the meeting.
There are also concerns about the safety of continuing to operate a nuclear plant in California, with its radioactive waste stored in concrete casks on the site. Diablo Canyon is subject to ground shaking and earthquake hazards, including from the nearby Hosgri Fault and the Shorline Fault, about 2.5 miles and 1 mile from the facility, respectively.
PG&E says the plant has been built to withstand hazards. It completed a seismic hazard assessment in 2024, and determined Diablo Canyon is safe to continue operation through 2030. The Coastal Commission, however, found if the plant operates longer, it would warrant further seismic study.
A key development for continuing Diablo Canyon’s operation came in 2022 with Senate Bill 846, which delayed closure by up to five additional years. At the time, California was plagued by rolling blackouts driven extreme heat waves, and state officials were growing wary about taking such a major source of power offline.
But California has made great gains in the last several years — including massive investments in solar energy and battery storage — and some questioned whether the facility is still needed at all.
Others said conserving thousands of acres of land still won’t make up for the harms to the ocean.
“It is unmitigatable,” said David Weisman, executive director of the nonprofit Alliance for Nuclear Responsibility. He noted that the Coastal Commission’s staff report says it would take about 99 years to balance the loss of marine life with the benefits provided by 4,500 acres of land conservation. Twenty more years of operation would take about 305 years to strike that same balance.
But some pointed out that neither the commission nor fisheries data find Diablo’s operations cause declines in marine life. Ocean harm may be overestimated, said Seaver Wang, an oceanographer and the climate and energy director at the Breakthrough Institute, a Berkeley-based research center.
In California’s push to transition to clean energy, every option comes with downsides, Wang said. In the case of nuclear power — which produces no greenhouse gas emissions — it’s all part of the trade off, he said.
“There’s no such thing as impacts-free energy,” he said.
The Coastal Commission’s vote is one of the last remaining obstacles to keeping the plant online. PG&E will also need a final nod from the Regional Water Quality Control Board, which decides on a pollution discharge permit in February.
The federal Nuclear Regulatory Commission will also have to sign off on Diablo’s extension.
Science
In search for autism’s causes, look at genes, not vaccines, researchers say
Earlier this year, Health and Human Services Secretary Robert F. Kennedy Jr. pledged that the search for autism’s cause — a question that has kept researchers busy for the better part of six decades — would be over in just five months.
“By September, we will know what has caused the autism epidemic, and we’ll be able to eliminate those exposures,” Kennedy told President Trump during a Cabinet meeting in April.
That ambitious deadline has come and gone. But researchers and advocates say that Kennedy’s continued fixation on autism’s origins — and his frequent, inaccurate claims that childhood vaccines are somehow involved — is built on fundamental misunderstandings of the complex neurodevelopmental condition.
Even after more than half a century of research, no one yet knows exactly why some people have autistic traits and others do not, or why autism spectrum disorder looks so different across the people who have it. But a few key themes have emerged.
Researchers believe that autism is most likely the result of a complex set of interactions between genes and the environment that unfold while a child is in the womb. It can be passed down through families, or originate with a spontaneous gene mutation.
Environmental influences may indeed play a role in some autism cases, but their effect is heavily influenced by a person’s genes. There is no evidence for a single trigger that causes autism, and certainly not one a child encounters after birth: not a vaccine, a parenting style or a post-circumcision Tylenol.
“The real reason why it’s complicated, the more fundamental one, is that there’s not a single cause,” said Irva Hertz-Picciotto, a professor of public health science and director of the Environmental Health Sciences Center at UC Davis. “It’s not a single cause from one person to the next, and not a single cause within any one person.”
Kennedy, an attorney who has no medical or scientific training, has called research into autism’s genetics a “dead end.” Autism researchers counter that it’s the only logical place to start.
“If we know nothing else, we know that autism is primarily genetic,” said Joe Buxbaum, a molecular neuroscientist who directs the Seaver Autism Center for Research and Treatment at the Icahn School of Medicine at Mount Sinai. “And you don’t have to actually have the exact genes [identified] to know that something is genetic.”
Some neurodevelopment disorders arise from a difference in a single gene or chromosome. People with Down syndrome have an extra copy of chromosome 21, for example, and Fragile X syndrome results when the FMR1 gene isn’t expressed.
Autism in most cases is polygenetic, which means that multiple genes are involved, with each contributing a little bit to the overall picture.
Researchers have found hundreds of genes that could be associated with autism; there may be many more among the roughly 20,000 in the human genome.
In the meantime, the strongest evidence that autism is genetic comes from studies of twins and other sibling groups, Buxbaum and other researchers said.
The rate of autism in the U.S. general population is about 2.8%, according to a study published last year in the journal Pediatrics. Among children with at least one autistic sibling, it’s 20.2% — about seven times higher than the general population, the study found.
Twin studies reinforce the point. Both identical and fraternal twins develop in the same womb and are usually raised in similar circumstances in the same household. The difference is genetic: identical twins share 100% of their genetic information, while fraternal twins share about 50% (the same as nontwin siblings).
If one fraternal twin is autistic, the chance that the other twin is also autistic is about 20%, or about the same as it would be for a nontwin sibling.
But if one in a pair of identical twins is autistic, the chance that the other twin is also autistic is significantly higher. Studies have pegged the identical twin concurrence rate anywhere from 60% to 90%, though the intensity of the twins’ autistic traits may differ significantly.
Molecular genetic studies, which look at the genetic information shared between siblings and other blood relatives, have found similar rates of genetic influence on autism, said Dr. John Constantino, a professor of pediatrics, psychiatry and behavioral sciences at the Emory University School of Medicine and chief of behavioral and mental health at Children’s Healthcare of Atlanta.
Together, he said, “those studies have indicated that a vast share of the causation of autism can be traced to the effects of genetic influences. That is a fact.”
Buxbaum compares the heritability of autism to the heritability of height, another polygenic trait.
“There’s not one gene that’s making you taller or shorter,” Buxbaum said. Hundreds of genes play a role in where you land on the height distribution curve. A lot of those genes run in families — it’s not unusual for very tall people, for example, to have very tall relatives.
But parents pass on a random mix of their genes to their children, and height distribution across a group of same-sex siblings can vary widely. Genetic mutations can change the picture. Marfan syndrome, a condition caused by mutations in the FBN1 gene, typically makes people grow taller than average. Hundreds of genetic mutations are associated with dwarfism, which causes shorter stature.
Then once a child is born, external factors such as malnutrition or disease can affect the likelihood that they reach their full height potential.
So genes are important. But the environment — which in developmental science means pretty much anything that isn’t genetics, including parental age, nutrition, air pollution and viruses — can play a major role in how those genes are expressed.
“Genetics does not operate in a vacuum, and at the same time, the impact of the environment on people is going to depend on a person’s individual genetics,” said Brian K. Lee, a professor of epidemiology and biostatistics at Drexel University who studies the genetics of developmental disorders.
Unlike the childhood circumstances that can affect height, the environmental exposures associated with autism for the most part take place in utero.
Researchers have identified multiple factors linked to increased risks of the disorder, including older parental age, infant prematurity and parental exposure to air pollution and industrial solvents.
Investigations into some of these linkages were among the more than 50 autism-related studies whose funding Kennedy has cut since taking office, a ProPublica investigation found. In contrast, no credible study has found links between vaccines and autism — and there have been many.
One move from the Department of Health and Human Services has been met with cautious optimism: even as Kennedy slashed funding to other research projects, the department in September announced a $50-million initiative to explore the interactions of genes and environmental factors in autism, which has been divided among 13 different research groups at U.S. universities, including UCLA and UC San Diego.
The department’s selection of well-established, legitimate research teams was met with relief by many autism scientists.
But many say they fear that such decisions will be an anomaly under Kennedy, who has repeatedly rejected facts that don’t conform to his preferred hypotheses, elevated shoddy science and muddied public health messaging on autism with inaccurate information.
Disagreements are an essential part of scientific inquiry. But the productive ones take place in a universe of shared facts and build on established evidence.
And when determining how to spend limited resources, researchers say, making evidence-based decisions is vital.
“There are two aspects of these decisions: Is it a reasonable expenditure based on what we already know? And if you spend money here, will you be taking money away from HHS that people are in desperate need of?” Constantino said. “If you’re going to be spending money, you want to do that in a way that is not discarding what we already know.”
Science
Contributor: New mothers are tempted by Ozempic but don’t have the data they need
My friend Sara, eight weeks after giving birth, left me a tearful voicemail. I’m a clinical psychologist specializing in postpartum depression and psychosis, but mental health wasn’t Sara’s issue. Postpartum weight gain was.
Sara told me she needed help. She’d gained 40 pounds during her pregnancy, and she was still 25 pounds overweight. “I’m going back to work and I can’t look like this,” she said. “I need to take Ozempic or something. But do you know if it’s safe?”
Great question. Unfortunately researchers don’t yet have an answer. On Dec. 1, the World Health Organization released its first guidelines on the use of GLP-1 receptor agonists such as Ozempic, generically known as semaglutide. One of the notable policy suggestions in that report is to not prescribe GLP-1s to pregnant women. Disappointingly, the report says nothing about the use of the drug by postpartum women, including those who are breastfeeding.
There was a recent Danish study that led to medical guidelines against prescribing to patients who are pregnant or breastfeeding.
None of that is what my friend wanted to hear. I could only encourage her to speak to her own medical doctor.
Sara’s not alone. I’ve seen a trend emerging in my practice in which women use GLP-1s to shed postpartum weight. The warp speed “bounce-back” ideal of body shapes for new mothers has reemerged, despite the mental health field’s advocacy to abolish the archaic pressure of martyrdom in motherhood. GLP-1s are being sold and distributed by compound pharmacies like candy. And judging by their popularity, nothing tastes sweeter than skinny feels.
New motherhood can be a stressful time for bodies and minds, but nature has also set us up for incredible growth at that moment. Contrary to the myth of spaced-out “mommy brains,” new neuroplasticity research shows that maternal brains are rewired for immense creativity and problem solving.
How could GLP-1s affect that dynamic? We just don’t know. We do know that these drugs are associated with changes far beyond weight loss, potentially including psychiatric effects such as combating addiction.
Aside from physical effects, this points to an important unanswered research question: What effects, if any, do GLP-1s have on a woman’s brain as it is rewiring to attune to and take care of a newborn? And on a breastfeeding infant? If GLP-1s work on the pleasure center of the brain and your brain is rewiring to feel immense pleasure from a baby coo, I can’t help but wonder if that will be dampened. When a new mom wants a prescription for a GLP-1 to help shed baby weight, her medical provider should emphasize those unknowns.
These drugs may someday be a useful tool for new mothers. GLP-1s are helping many people with conditions other than obesity. A colleague of mine was born with high blood pressure and cholesterol. She exercised every day and adopted a pescatarian diet. Nothing budged until she added a GLP-1 to her regimen, bringing her blood pressure to a healthy 120/80 and getting cholesterol under control. My brother, an otherwise healthy young man recently diagnosed with a rare idiopathic lymphedema of his left leg, is considering GLP-1s to address inflammation and could be given another chance at improving his quality of life.
I hope that GLP-1s will continue to help those who need it. And I urge everyone — especially new moms — to proceed with caution. A healthy appetite for nutritious food is natural. That food fuels us for walks with our dogs, swims along a coastline, climbs through leafy woods. It models health and balance for the young ones who are watching us for clues about how to live a healthy life.
Nicole Amoyal Pensak, a clinical psychologist and researcher, is the author of “Rattled: How to Calm New Mom Anxiety With the Power of the Postpartum Brain.”
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