But now there are interlopers: Drug middlemen, companies known as pharmacy benefit managers (PBMs) that influence which medicines can be bought, where to buy them and at what cost.

Patel and other independent pharmacists say their businesses are threatened by the growing influence of these companies, tied to huge health care conglomerates. In a system that is opaque and complex, patients are steered to affiliated pharmacies, such as CVS and mail-order pharmacies, they say. Pharmacists face high fees and low reimbursement rates, so are unable to cover their costs.

That could put Patel — and other locally-owned pharmacists — out of business.

“I want to do what matters to the community. But how long can I sustain this?” said Patel, 48, who owns Savco Pharmacy in San Jose’s West San Carlos neighborhood. “We are at their mercy.”

The PBMs respond that critics base their conclusions on incomplete evidence. According to the trade organization Pharmaceutical Care Management Association, they protect consumers from high drug prices by negotiating for discounts, called rebates, from drug companies.

The disappearance of independent pharmacies could limit consumer choice and health care access — especially in low-income or rural communities.

On Oakland’s Telegraph Avenue, Selam Pharmacy owner Michael Gebru called PBMs “a big black box.” He said “They bill me whatever they want, and can reclaim it. That’s pretty scary. It’s a Wild West.”

In the coastal village of Point Reyes Station, tiny West Marin Pharmacy recently lost its contract with PBM company Express Scripts, used by insurer Cigna and others. Now residents covered by Cigna must get their prescriptions by mail or make a 20-mile drive to find another pharmacy.

“If any of us, our children and families are ill, suffering from fevers, vomiting, diarrhea or worse, we may be forced to drive an hour or more to San Rafael, Novato or Petaluma just to get a prescription filled,” worried pharmacy customer Christine Cordaro of Inverness Park.

PBMs were created in the 1960s as a way to process prescription drug claims. They are responsible for paying pharmacies on behalf of insurance companies, employers and the government. The three largest companies are run by CVS Health, Cigna and UnitedHealth Group, which oversee prescriptions for more than 200 million Americans.

In 2012, the year San Jose pharmacist Patel bought his modest shop, PBMs processed fewer than 50% of prescriptions.

A series of mergers in 2018 created the current system, where health care conglomerates are vertically integrated — owning the insurer, the PBM and pharmacy. The giant health insurer Aetna combined with drug retailer CVS. Another large insurer, Cigna, bought Express Scripts. UnitedHealth built its own PBM.  All three companies operate mail-order pharmacies.

“It’s like they’re taking the money from one pocket, and putting it into the other,” said Zsuzsanna Biran, pharmacist owner of West Marin Pharmacy.

Despite consumer opposition, the FTC approved the mergers.  But now there are concerns about PBMs’ economic leverage. The smaller, locally owned pharmacies feel muscled out of the market.

CVS calls the plight of independent pharmacies “overblown.”

“Contrary to much of the independent pharmacy lobby’s rhetoric, there is no crisis facing independent pharmacies,” CVS said in a statement.

“What the independent pharmacy lobby has long coveted is a world without managed pricing or the competitive pressure from PBM negotiations on behalf of payer clients and consumers,” CVS said.

According to Express Scripts, “If we didn’t provide significant value for our thousands of partners, we wouldn’t exist.”

The PBMs work by negotiating rebates on the “sticker price” of medicines. Some of these savings are shared with insurers and employers.  But a slice is kept by the PBMs. This is enormously profitable.

There is evidence of anticompetitive behavior that illegally distorts the market, hurting consumers and threatening the survival of independent pharmacies, according to new reports by the U.S. Federal Trade Commission and a House Committee on Oversight and Accountability investigation.

PBMs steer patients toward pricier drugs, with “formularies” of preferred medicines that discourage use of lower-priced alternatives, according to the reports, released last month. Because these high-priced drugs command a greater rebate, there’s more profit.

They also sometimes restrict patients’ access to mail-order deliveries, which they own. This cuts out the role of the local pharmacy.

Independent pharmacies say they’re saddled with unnecessary extra fees. When he started his business in 2012, Patel paid $15,000 to $20,000 in PBM fees; this year, his fees could surpass $110,000.

High fees and low reimbursement may discourage pharmacists from filling a prescription. If he loses money on a prescription, “I have two options,” said Patel. “Take the loss, or tell the patient that I cannot fill it.”

“With lower prescription reimbursements in one corner and higher back-end fees in the other, many community pharmacists are thinking about throwing in the towel,”  according to the National Community Pharmacists Association, which represents more than 19,400 independent U.S. pharmacies.

Nearly one-third of independent pharmacy owners may close their stores this year, it predicted.

But in Sacramento and other state capitals, lawmakers are taking a tougher look.

State Sen. Scott Wiener has authored legislation, Senate Bill 966, that would impose new rules on PBMs, better regulating the companies. It would require PBMs to be licensed with the California State Board of Pharmacy and to pass down drug rebates to consumers.

Meanwhile, Patel takes joy in things that don’t cost money — recognizing customers’ names and faces, making birthday phone calls and reminding them to be immunized. Once he provided a cane, for free, to a customer with a gimpy leg.

And there are rewards that are priceless, such as the gifts of fruit, chocolate and home-baked cookies from grateful customers.

“He’s the best,” said customer Rob Souza, picking up a prescription for an ailing wife. “He’s like a small-town pharmacist, always working things out.”

But how much does going solar shave off those electricity bills? A major new study by scientists at Lawrence Berkeley National Laboratory that analyzed 500,000 households across the U.S. in 2021 offers the best snapshot to date on estimated savings of rooftop solar for American consumers.

The study found the median American household saved an estimated $691 a year when all the costs and benefits were included.

“This is one of the most comprehensive, household-specific, national estimates of rooftop solar impacts on household energy burden,” said lead investigator Sydney Forrester, a policy researcher in the Energy Markets and Policy Department at the Laboratory, a federally funded research and development center in the hills of Berkeley.

Much previous research has focused only on direct utility bill savings of solar power, which can be misleading. For instance, if the cost of installation is excluded, the median household would erroneously calculate $1,987, not $691, in savings.

The new study provides a more complete accounting because it includes upfront installation fees and ongoing loan or lease payments, as well as any solar incentives. And it compares the benefits reaped by households with different incomes.

Nationwide, installation of solar panels in low-income households reduced the proportion of the family budget spent on energy from 7.7% to 6.2%, an estimated savings of $660 a year, the study said. In moderate-income households, it reduced the the proportion they spent on energy from 4.1% to 3.3%, saving $674 a year. And in higher-income households, the amount spent on energy dropped from 2.4% to 1.9%, saving $711 a year.

The study did not look at actual savings, because that data is not available. Rather, it modeled the household savings based on estimates of income, household utility bills, local electricity prices and consumption. Almost everyone in the study was a single family homeowner, with a few multifamily or rental homes.

Not every home reaps a benefit from solar power, the researchers found. On average, solar adoption reduced the cost of energy for about three-quarters of  U.S. households.

The benefits of solar power varied by region. In the West, especially California, high electricity prices and a competitive solar marketplace led to the greatest cost reduction. Homes in the Midwest experienced lower costs, although they were less pronounced. Homes in the Northeast also saw a benefit, although their overall energy costs remain high due to dependence on non-electric sources, such as propane and fuel oil.

In the South, solar power actually increased the overall cost of energy, because electricity prices from conventional sources are so low. For low-income Southern families, the cost of solar exceeded the benefit by $435 a year.

Low-income residents in the U.S. West who have installed solar power experience the greatest benefit with the proportion of estimated household income spent on energy falling from 7.3% to as much as 5.7%, saving an estimated $821 a year.

But low-income residents continue to need assistance to help reduce energy costs, the researchers added.

“Solar is a great strategy for reducing energy costs,” Forrester said. But he added that it “should be considered as a complementary strategy” along with bill assistance and “weatherization” that helps insulate homes.

And Forrester cautioned that “while low-income households benefit more than other groups, there is a risk if they fall behind on payments to finance the projects.”

Power bills have been rising across the nation. The average price of electricity per kilowatt hour has jumped from 13 cents to over 17 cents over the past decade, according to data from the Bureau of Labor Statistics. California’s residential rates are far higher — close to 30 cents, second highest in U.S. behind Hawaii.

Energy costs are typically a bigger burden for low-income households, which tend to spend a far larger percentage of their income on utility bills than higher-earning households, according to the Energy Department.  Many live in old and drafty homes and cannot afford modern and more efficient appliances.

“I applaud the paper’s overall goal, which is to raise awareness about the potential for rooftop solar to help alleviate energy burden for low-income disadvantaged community households,” said Eric Daniel Fournier, research director of the California Center for Sustainable Communities at UCLA’s Institute of the Environment and Sustainability. “We strongly believe in the potential of rooftop solar… to address this important equity issue.”

The benefits of rooftop solar for low income households are most prominent in areas with higher electricity rates, such as California, he added.

Stanford University’s Ram Rajagopal, director of the Stanford Sustainable Systems Lab, called the findings “extremely valuable.”

“It shows that the cost of energy that you get from rooftop solar is very competitive for low and middle income consumers,” he said. “It reduces their energy burden, given access to the right incentives.”

The study is also important because it stresses the need for additional strategies, such as weatherization and bill assistance, said Rajagopal.  His research, published in the March issue of the journal Nature Energy, has also shown that commercial and industrial rooftops, such as those atop retail buildings and factories, have large unused capacity to produce solar power  — and could bring affordable clean energy to low-income communities around them, reducing “the solar equity gap.”

The study falls short by not describing the practical barriers to the implementation of rooftop solar within low-income disadvantaged communities, Fournier noted. It also didn’t include any savings created by energy storage components — backup battery systems, he added. California policy now encourages the parallel adoption of solar panels and power storage units.

In future work, the Laboratory team will study the potential of solar savings for a broader variety of homes, including renters and multifamily dwellers, Forrester said. She hopes to expand the study to include “community solar” and other strategies that don’t require rooftop ownership.

What’s missing, she added, are low-income residents who would like to save money on energy bills but couldn’t afford the upfront costs.

“Any additional cost to solar adoption will increase the barrier,” she said, “and this is more likely in the case of older homes or those with deferred maintenance.”

But here’s why the new shot, recommended by FDA advisers last week, makes sense: It targets a new version of the virus, the FDA panel said. It bolsters your body’s ever-growing defense system.  And it’s a lot better than getting very sick or hospitalized.

Last year’s shot isn’t holding up. Protection against both infection and severe illness is waning.

“Effectiveness has decreased, as the time since vaccination has increased — and as new SARS-CoV-2 variants emerge,” said biostatistician Danyu Lin of the University of North Carolina School of Global Public Health, who presented worrisome new data to the FDA advisory panel.

The old vaccine’s effectiveness peaked one month after the shot, Lin’s team found. After four weeks, the vaccines were 52.2% effective at preventing infection and 66.8% effective at preventing hospitalization. After ten weeks, effectiveness at preventing infection decreased to 32.6% while effectiveness at preventing hospitalization decreased to 57.1%.

By comparison, the Centers for Disease Control and Prevention says that with the annual influenza shot, “during seasons when flu vaccine viruses are similar to circulating flu viruses, flu vaccine has been shown to reduce the risk of having to go to the doctor with flu by 40% to 60%.”

Last Wednesday, FDA’s advisers, a panel of physicians from hospitals and universities around the nation, unanimously voted to recommend a new vaccine. Vaccine manufacturers Pfizer and Moderna say they were prepared to make updated vaccines available in August, pending final FDA approval. As in previous years, the U.S. Centers for Disease Control will make specific recommendations for the elderly, immunocompromised, youth and other groups.

The new vaccine will target a variant of the ever-evolving coronavirus called JN.1. Last year’s vaccine was based on the XBB lineage of the virus.

Fortunately, the COVID virus isn’t changing in a way that would make it a serious threat to most people — turning it into something far deadlier, such as Ebola. Each new version is a subvariant of the omicron variant that first appeared in 2021 and, though highly transmissible, hasn’t proven to be particularly virulent.

But it is drifting in smaller ways, complicating our vaccine strategy. The original virus first detected in Wuhan, China, was replaced by the alpha variant, which was replaced by the delta variant, which was replaced by the omicron variant. A subvariant called BA.1, then BA.2, became the most common circulating versions of omicron.

Since then, the virus family has continued to multiply and diversify. There’s an evolutionary arms race — as the immune system makes new antibodies, the virus develops new mutations. Each iteration seeks to offer some sort of advantage, such as an ability to sidestep the immune system or extreme contagiousness.

Late in 2023, variant JN.1 overtook the XBB lineage.

There’s a wrinkle in the new vaccine strategy: By next fall, JN.1 may not be the dominant virus. Already, a subvariant called KP.2 is on the rise. But the new vaccine formula likely will be effective against both strains — and, because manufacturing takes time, a decision must be made now.

When compared against results from the original shot, the benefit of the new shot may seem modest. That’s because the original vaccines were given to a completely unprotected population, with high risk of hospitalization and death, said Lin. Now, with four years of inoculations and infections, the general population has a wide range of vulnerabilities.

While the vaccine is free to both insured and uninsured individuals, this cost is still real. The federal government paid, on average, $20.69 per dose, and the cost of the new vaccine is likely to be higher. But vaccines save money by preventing hospitalization, lost productivity due to illness and potential Long COVID.

Research is now underway to create a universal vaccine that works against all strains of the virus.

Powerful combination vaccines are on the horizon, easing the chore of multiple shots. On Monday, Moderna announced that, in a Phase 3 clinical trial, its combination COVID and influenza vaccine generated stronger immune responses in older adults than individual vaccines targeting those viruses individually. A combo shot could be on the market as early as autumn 2025.

The FDA news comes as Americans are vaccine-weary and increasingly indifferent. The Centers for Disease Control and Prevention estimates that, as of March, a mere 28% of American adults have been vaccinated with the latest vaccine. Why bother with another shot? Medical experts say there are still many reasons to get the jab:

• Protection from previous shots, especially the primary series, has waned — so some people are getting very sick. Research shows that a large percentage of those hospitalized for COVID-19 had been vaccinated with the primary series but hadn’t gotten an updated shot.

• Each additional shot helps. There is evidence that each vaccine or infection, especially in the first few months after receipt, provides added protection against critical illness and hospitalization. “Through multiple immunizations, your repertoire of immune cells expands,” said Jeremy Kamil, a virologist at Louisiana State University Health Sciences Center Shreveport, who studies variant mutations. “Your body learns to make these very potent antibodies that are active against multiple strains of the virus, so it becomes harder for the virus to wiggle away from them. … You’re much better defended.”

• If you get infected, it will likely be less severe. Think of seatbelts and airbags — they don’t prevent car crashes, but they boost your chance of survival. Similarly, COVID vaccines are not 100% protective, but an immune response will be more vigorous, so your illness will likely be briefer. Furthermore, research shows that vaccines help protect against Long COVID.

• Vaccines are easier on your body than infection. A sore arm and perhaps body chills are better than days of illness and perhaps hospitalization. “You’re setting yourself up for success the next time you see the virus,” said Kamil. “Your immune system will say, oh, I gotcha. I know who you are.”

One of the rarest whales in the world, only an estimated 30 animals are thought to survive.

“It was astonishing,” said research ecologist Jan Roletto, who sighted the whale about three miles west of Point Reyes National Seashore while aboard a research vessel for the Applied California Current Ecosystem Studies.

Visibility was tough on Friday, with waves and fierce winds that pushed 12 to 14-foot swells. The mission of the research team’s weeklong trip, a partnership between Greater Farallones and Cordell Bank National Marine Sanctuaries and Point Blue Conservation Science, was to survey marine wildlife.

But the whale was unmistakable.

“It came up right in front of us,” then lingered for nearly 20 minutes, said Roletto, research coordinator for the Greater Farallones and Cordell Bank National Marine Sanctuaries.

Standing together on the ship’s viewing platform, Roletto and marine ecologist Kirsten Lindquist instantly turned to look at each other.

“We both knew immediately what it was,” Roletto said. The identification has since been officially confirmed by the NOAA Marine Mammal Lab in Seattle, based on photos and video.

The whale had a distinctive V-shaped blow. Wide and pitch black, it had no dorsal fin. And there was at least one cluster of telltale “callosities” on the head, rough and white skin patches.

“It seemed to be resting,” Roletto said. “It wasn’t feeding. It wasn’t traveling. It would move a little bit, then sink down.”

They once numbered in the tens of thousands throughout the North Pacific.

Like other whales, the species was driven nearly to extinction by commercial whaling in the 1800s. Hunters named them the “right” whale to kill because they’re easy targets. They swim slowly and near shore, have thick blubber and float when killed, according to Jessica Crance, a research biologist with the Cetacean Assessment and Ecology Program at the Alaska Fisheries Science Center. It is estimated that between 21,000 – 30,000 right whales were slaughtered in the North Pacific in a single decade.

By 1900 they were already considered commercially extinct – meaning their numbers were so low they weren’t worth the effort of trying to catch.

The International Convention for the Regulation of Whaling banned the commercial hunting of right whales in the North Pacific in 1937, and their numbers began to climb.

But illegal Soviet whaling in the 1960s in the northern Gulf of Alaska and Bering Sea again pushed the species toward extinction.

They have been protected under the Endangered Species Act since 1970. But unlike other species of whales — such as humpbacks, gray whales and blue whales — populations of the North Pacific right whale have been much slower to recover. Its cousin in the Southern Hemisphere is faring somewhat better.

While whaling is no longer a threat, human activity such as entanglement in fishing gear and marine debris, vessel strikes, impacts from climate change, oil and gas development and ocean noise continue to threaten the species.

According to Crance, there are only an estimated 30 individuals left in U.S. waters, and that number was based on data that is more than 15 years old.

“When their historical distribution is in a remote region with notoriously bad weather, finding even a single animal becomes a search for the proverbial ‘needle in a haystack,’ ” Crance wrote in the Journal of the American Cetacean Society.

North Pacific right whales are baleen whales, which feed by straining huge volumes of ocean water through their comb-like baleen plates that trap copepods and other zooplankton.

Because they are so rare, very little is known about the movements, migration, breeding or calving of the North Pacific species, said Jim Scarff, an independent whale researcher in Berkeley. Satellite tagging offered detailed movement data when the whales were in the Bering Sea, but all tags fell off before the animals left the region, so their travel routes remain a mystery.

“There is remarkably little understanding about their distribution,” said Scarff..

Acoustic surveys offer a new approach to track the whales. Using specialized software, U.S. and Canadian biologists are now collaborating in an acoustic study to detect right whale calls along the British Columbia coast.

But vessel-based surveys are still the best means for obtaining information on an individual animal, according to Crance.

In the past decade, there have been a handful of detections off the coasts of British Columbia, Washington State and California. In March 2023, whale watchers saw one close to shore near Point Pinos in Monterey Bay. In April 2022, a fisherman reported a sighting near San Mateo County’s Point Ano Nuevo.

“It’s always one individual animal, often in the spring,” said Scarff. “And then it’s never seen again.”

_______

©2024 MediaNews Group, Inc. Visit at mercurynews.com. Distributed by Tribune Content Agency, LLC.

Now comes the bill.

Last month, Stanford became the first hospital in the nation to use a new $515,000 cell therapy to treat a patient with advanced melanoma. A related approach, costing $420,000 to $475,000, is offering hope to patients with lethal blood cancers.

Meanwhile, cells fixed by gene therapy can slow, even stop, the progression of intractable diseases like sickle cell or beta thalassemia — for the extraordinary price of $2.1 million to $4.25 million each.

This is the future of medicine, experts agree. But the cost of this new class of medical treatment is raising alarm about availability and affordability, even as its potential grows. It’s time to re-imagine our payment models, they said.

“Cell and gene therapies have the possibility to transform thousands of lives but only if we ensure sustainable access to them for all patients,” said Sarah Emond, president of the influential Institute for Clinical and Economic Review, a Boston-based nonprofit that assesses the value of medicines.

The prices aren’t yet unmanageable, because so few people are currently treated. Patients must travel to designated treatment centers, and too few are referred by community physicians. But demand should increase as more treatments are introduced that serve a wider population.

Most health insurers in the United States aren’t set up to support one-time personal therapies that deliver long-term benefits, at unprecedented prices.

“These are precision medicines,” said Dr. David Miklos, chief of the Stanford Bone Marrow and Cell Therapy Program, where hundreds of cancer patients have been treated with the CAR-T cell therapies. “It’s different than buying a pill at the CVS pharmacy that can work for anybody.”

It is a triumph decades in the making. The promise of cell and gene therapies has ​long intrigued scientists​, but progress was slow, with many setbacks. Now FDA-approved products are entering the clinic.

“The technology to bring it to life has finally caught up with the ideas behind it,” said Stanford assistant professor of medicine Dr. Allison Betof Warner, who is conducting Stanford’s melanoma trial.

Cell-based strategies are delivering the most celebrated cancer treatments to emerge in decades.

In one approach, called chimeric antigen receptor (CAR) T-cell therapy, patients’ immune cells are collected and genetically modified to better fight lymphoma, leukemia, and, most recently, multiple myeloma.

Another uses a different approach, enlisting tumor-infiltrating lymphocytes, or TILs. These immune cells are harvested from the tumor, fortified in the lab and then returned to the patient. In clinical trials, about 30% of patients had their incurable melanoma tumors shrink or disappear.

“I’m very happy that it’s here now. … I’ve been walking the tightrope and I didn’t fall off,” said a Stanford patient, who asked not to be identified.

Gene therapy also uses engineered cells, with genes replaced, deleted or inserted. On Wednesday, Kendric Cromer, a 12-year-old boy from a suburb of Washington, D.C., became the first person in the world with sickle cell disease to begin an FDA-approved gene therapy. Stanford and UCSF will both offer this treatment.

Scientists are now working to expand the therapies’ repertoire to attack solid tumors, autoimmune diseases, aging, HIV and more.

“It’s just the beginning of a new era,” said biochemist Wendell Lim, director of the UC San Francisco Cell Design Institute.

“It shows that we can take a living cell and change what it does, so it makes new sorts of decisions and carries out complex actions. It processes information, like a little computer,” he said. “This is very different from a static thing, like a chemical.”

It’s still early, and few patients are taking advantage of these new groundbreaking therapies, said physicians.

Why? Word hasn’t yet gotten out, so sick people aren’t getting referred from their community physicians, said Miklos. Treatment is risky. Or patients may live far away from the nation’s estimated 30 “centers of excellence,” like Stanford and UCSF, and are daunted by the cost of travel and housing.

Payment isn’t guaranteed; it’s decided on a case-by-case basis. Medicare and MediCal cover the cost of care when it is determined to be medically necessary.  So does Kaiser.

The great majority of private insurers cover treatments, although sometimes back-and-forth negotiations are needed, said Gary Goldstein, who oversees the business operations of Stanford’s Blood & Marrow Transplant Program.

The sticker price just covers parts — no labor, no warranty. Drug prices aren’t regulated, like utilities, and there is no cap on what a company can charge.

The total cost for gene therapies over the next decade has been estimated to reach an eye-popping $35 billion to $40 billion. The bill for future cell therapies, which could help a bigger pool of patients, will likely be higher.

Drug makers argue that the prices reflect the powerful clinical benefit and the risks and uncertainties of development. A one-time therapy for a chronic condition may actually save money, they add, by sparing a lifetime of care.

“We’ve never cured patients with a single treatment before,” said UCSF’s Dr. Greg Allen, who is designing immune cell therapies for notoriously difficult-to-treat tumors, like those of the pancreas and lung. “So it’s very exciting.”

For some patients, it may be their last best chance.

“I don’t think there’s a price on a life,” said Stanford’s Betof Warner. “These are patients who don’t have another option.”

If millions of people are helped, as hoped, it will create budget pressures on the federal government and larger payers, while smaller employers, state Medicaid plans, and regional health plans may find providing access financially impossible, warn economists. Health care costs are already outpacing inflation, climbing 7% this year.

“It’s going to put a lot of stress on the system,” said Edwin Park at the Georgetown University McCourt School of Public Policy.  “But the issue is critical because you don’t want the high price of these therapies to result in low-income people not being able to access them.”

Already, governments and commercial insurers are scrutinizing treatments’ effectiveness. Some are imposing strict restrictions on who is eligible. They’re asking manufacturers for discounts and rebates.

Scientific advances could cut costs, said Lim. One idea is to design cells that are immunologically universal, so that a single source could treat many patients. Another is to build a large “cell bank” of precursor stem cells. A third is to ask the body to do its own manufacturing, by introducing an engineered virus that can fix cells.

If manufacturing is localized — making the cells at Stanford or UCSF, for instance, rather than at distant drug companies — that would bring costs down, said Miklos.

As competition grows, prices will fall, he predicted.

Meanwhile, the health care system must focus on finding innovative payment solutions, said Emond.

One proposal is to amortize how much insurers pay over time, like a home mortgage. Another is for drug companies to provide a prorated refund if a patient doesn’t improve — a “pay for performance” model. Yet another option would be a subscription-based approach, like Netflix, where insurers shell out a monthly fee to access however much therapy is needed.

Each condition, therapy and payer is unique, so a single solution won’t satisfy all situations.

“As we look to the future,” said Emond, “this is a moment where we can discuss how to do things differently.”

Now we’re in a modern-day growth spurt.

A new study by researchers at UC Davis Health found that the brains of people born in the 1970s had 6.6% larger volumes and almost 15% greater brain surface area than those of people born in the 1930s.

“We found that brains got larger with each 10 years,” said neurologist Dr. Charles DeCarli, principal investigator of the study, published in a recent issue of the journal JAMA Neurology. It was based on an analysis of thousands of volunteers in the famed Framingham Heart Study.

This doesn’t prove that we’re getting smarter, although other studies suggest that trend. In the human brain, size isn’t everything; wiring matters, too.

But bigger brains could increase so-called “mental reserve,” potentially reducing the overall risk of age-related dementia, according to DeCarli. Perhaps it explains a recent decrease in the percentage of people affected by Alzheimers disease, as reported in the 2016 New England Journal of Medicine.

“It may accommodate more of the connections that help organize the brain and make it more resilient, leading to a better ability to withstand aging,” he said.

The Framingham Heart Study, over seven decades old, keeps data on thousands of people living in Framingham, Massachusetts. It is the longest-running and most comprehensive project of its kind in medical history.

To study brain changes, the Davis scientists didn’t measure the squishy three-pound blob inside each human skull. Rather, they measured brain scans of 3,226 individuals obtained by MRI, which painlessly reveals the brain’s structure. The MRIs were conducted between 1999 and 2019 on more than 3,000 healthy Framingham residents born between the 1930s and 1970s, with an average age of about 57.

They then compared the images of people from three different eras: the Silent Generation of the 1930s, baby boomers of the 1950s, and Generation X, born in the 1970s.

Their analysis found that the brain’s volume and surface area were not the only regions to grow over time. Two other key areas — white matter, which contains connective fibers and delivers nerve signals, and the hippocampus, which processes memory – have also grown between 5.7% to 7.7%.

The increase in white matter suggests that brain cells are more interconnected, DeCarli said.

The increase isn’t explained by growth of the rest of the body. People born in the 1930s had a mean height of 66 inches, compared with 67.6 inches for those born in the 1970s. But even after adjusting for height, brains were bigger.

While there’s been an incremental upward drift in IQ test scores — approximately 3 points per decade — across generations, that may reflect improvement in education, life experiences and test-taking, not intelligence. It’s difficult to compare the intelligence of different generations, DeCarli said.

Scientists have long studied the evolutionary history of our brain to understand how and when it grew, allowing sophisticated skills to emerge. The human brain is gigantic relative to our body size. It’s three times as large as that of chimpanzees, our closest living relatives. It also has distinctive anatomical features.

At a pivotal time in human evolution, about 3 million to 4 million years ago, human brains dramatically increased in size. A set of three nearly identical genes seem to play a critical role in this development, according to a study led by David Haussler, professor of biomolecular engineering and scientific director of the UC Santa Cruz Genomics Institute. Other mutations may also turn out to be important.

Early hominins like Sahelanthropus and Australopithecus have relatively small brains. Fossils of the first Homo species show larger brains. The brains of Homo sapiens — us — are bigger still.

But the growth detected by the Davis team isn’t attributable to evolution, said DeCarli. It’s too recent.

Rather, improving lifestyles — especially during the crucial first 10 years of life, when the brain is developing — deserve credit. The 20th century delivered dramatic improvements in the standard of living, education, nutrition and health care for many Americans.

“This cannot be a genetic effect. It more likely to be environmental,” said DeCarli. “We don’t know what those things are, but I suspect they have to do with better prenatal care, better nutrition, better education, maybe a more ‘enhanced’ environment.”

Experts not involved in the project said the findings were provocative.

“Although these findings are new to our field, the substantial gains over four decades are intriguing,” wrote Prashanthi Vemuri, a neuroimaging scientist at the Mayo Clinic who wrote an editorial accompanying the study. If verified, it is important to study what’s driving this trend, she said.

“Replication of these results in other cohorts is essential,” she said. “If these results are confirmed by others, and the observed differences by decade are as large as those reported, it has important implications for aging and dementia studies.”

The study has limitations. Its participants are healthy, well-educated and middle class. They’re almost all non-Latino whites, not reflecting the diverse U.S. population.

Finally, it didn’t include people who had deprived childhoods. If a bigger brain is protective, such inequalities could put them at greater risk of dementia.

“We haven’t looked at populations that suffer from adversity,” said DeCarli. “And I suspect that they’re not experiencing, over time, the same kind of changes.”

Four years after the U.S. went into lockdown, the worst of the pandemic has passed. But for people with long COVID, the illness remains a daily misery.

The new research suggests why: The virus is not always fully cleared after the initial infection, so remains deeply embedded, even though people are no longer contagious.

It is not yet known if these small viral proteins, called antigens, are causing long COVID. But, based on the new discovery, the UCSF team is conducting clinical trials of potential therapies that could attack the hidden pathogen.

“This can be a persistent infection for some people,” said Dr. Timothy Henrich, professor of medicine at UCSF who co-authored the research, presented at last week’s Conference on Retroviruses and Opportunistic Infections in Denver. “We’re concerned that this could be leading to, at least in part, some of the long COVID symptoms that people have been experiencing.”

While COVID remains much more serious than the usual seasonal flu, safe and highly effective vaccines have caused a dramatic decline in infections and deaths.

There is a desperate need for a diagnostic test and treatment for long COVID, which affects an estimated 7% of American adults. Currently, doctors are only treating the symptoms, rather than offering a cure. Experts predict that the disorder will place continuing demands on our healthcare system.

“Long COVID patients deserve swift, accurate diagnosis and timely, effective treatment,” said Jaime Seltzer, scientific director at the nonprofit MEAction, which advocates for patients with long COVID and myalgic encephalomyelitis/chronic fatigue syndrome, or ME/CFS.

Is the clandestine virus constantly provoking the immune system, causing symptoms? That’s one leading theory. Another possibility is that COVID triggers an autoimmune response when the body mistakenly attacks itself. Or perhaps, long after it fends off infection, the immune system fails to turn off.

Using an ultra-sensitive test of blood from 171 people who had been infected with COVID, the UCSF scientists found pieces of the viral “spike” protein that persisted up to 14 months after infection.

Viral proteins were identified in 7% to 14% of the patients.

The likelihood of detecting the protein was about twice as high in people who had been severely ill, requiring hospitalization, than those who were not, according to the team. Detection was also higher in the blood of people who reported being very sick, but were not hospitalized.

In a second study involving tissue samples, traces of the virus were found up to two years after infection. It hid in connective tissue where immune cells are located. The work was conducted at UCSF’s Long COVID Tissue Bank, the world’s first tissue bank with samples donated by patients with long COVID.

Patients are not infectious because the virus is not living in the respiratory tract, where it could be spread by coughing or sneezing, said UCSF’s Henrich. Instead, “there seems to ‘seeding’ of deeper tissue after the initial infection, that may persist over a long period of time.”

The team is now designing studies to target the persistent virus. Hopes are pinned on a monoclonal antibody – a lab-made protein that effectively attacks viruses – and an antiviral therapy that blocks viral replication.

“There is a lot more work to be done, but I feel like we are making progress in really understanding the long-term consequences of this infection,” according to infectious disease expert Dr. Michael Peluso, who led the UCSF study.

This is worrisome because these persistent active infections may act as viral “reservoirs” that lead to new and highly genetically divergent lineages, seeding a future outbreak.

That study found that the risk of long Covid was 55% higher in people with persistent infection.

“We’re making considerable headway on understanding what drives long Covid,”  wrote Dr. Eric Topol, director of the Scripps Research Translational Institute in La Jolla.

“Clearly finding effective and safe treatments is an urgent matter and not enough is being done to pursue that yet, despite a long list of potential alluring interventions based on mechanistic insights,” he said. “Hopefully that will get going now — it cannot happen soon enough.”

The study, published on Thursday in the journal Science, adds to our understanding of long COVID, the lingering and often debilitating symptoms experienced by some people. One significant finding revealed shifts in proteins the body produces in response to inflammation that may persist months after infection. Another detected blood clots and tissue injury.

“We identified common patterns in long COVID patients not recovered at six months after acute infection,” compared to healthy patients, wrote the team, a collaboration of scientists from New York City’s Icahn School of Medicine at Mount Sinai, Switzerland, Sweden and London.

There is tremendous need to diagnose and find effective ways to treat long COVID, a constellation of symptoms that include exhaustion, migraines, brain fog and nausea that are not explainable using conventional lab tests.

At a hearing in Washington D.C. this week, senators at the Senate Committee on Health, Education, Labor and Pension agreed that the government must become more involved in long COVID research and support. Sen. Tim Kaine, D-Va., said he has been struggling with symptoms of long COVID for four years.

On March 15, a demonstration is planned at Lincoln Memorial to raise awareness and urge greater funding, preventative measures, research, and treatment strategies.

Although long COVID’s prevalence is difficult to estimate, surveys suggest it may afflict 5.3% to 7.5% of people infected by the virus.  It’s not known why some people develop long COVID and others don’t. But vaccines offer protection. One dose of vaccine reduces risk by 21%, two doses reduce risk by 59%, and three or more doses reduce risk by 73%, according to a recent study.

What causes long COVID? One possibility is that, long after it fends off infection, the immune system is still fighting. It turns on — but doesn’t turn off.

Experts don’t know why. UC San Francisco research suggests that viral genetic material remains embedded in tissues, long after infection. Or perhaps COVID triggers an autoimmune response when the body mistakenly attacks itself. There is mixed evidence for the effectiveness of the antiviral drug Paxlovid in preventing long COVID.

There is a desperate need for a diagnostic test and treatment for long COVID. Currently, doctors are treating the symptoms, rather than the underlying cause.

The new findings are important because “they demonstrate dysfunction, which is important to patients,” said Jaime Seltzer, scientific director at the nonprofit MEAction, which advocates for patients with long COVID and myalgic encephalomyelitis/chronic fatigue syndrome, or ME/CFS.

“Secondly, they point the way to potential treatments, and even possibly mechanisms” of disease, she said.

This paper builds on our understanding of long COVID by connecting the changes that occur during an acute infection to longer-term abnormalities in markers of blood cell function, said Dr. Michael Peluso, an infectious disease physician at Zuckerberg San Francisco General Hospital, who is studying the biological mechanisms that drive long COVID and the infection’s long-term impact on health.

“It suggests that there is a relationship between the virus, its immune effects, and changes in certain blood coagulation pathways,” he said.

Although the study represents another step forward in understanding the science of long COVID, it will not immediately change the approach to diagnosing or treating the condition, said Peluso.

“We need more investment in larger studies to build upon these findings, as well as clinical trials to test whether altering some of the abnormalities that have been found here could result in symptomatic benefit,” he said.

In the new study, scientists analyzed changes in the blood of 113 patients who either fully recovered from COVID-19 or developed long COVID, as well as healthy people.

Specifically, they measured levels of 6,596 different proteins in study participants over a year, then sampled the blood again six months and a year later.  Proteins act like keys that fit in multiple locks on the surface of cells. Changes in proteins mean that cellular processes are altered.

Immune dysfunction is also suspected to be driving the symptoms in those with other persistent infection-linked illnesses, such as ME/CFS and Lyme Disease, said Seltzer. It’s the body’s way of adapting, she said.

There are caveats. With only 113 patients, the study was relatively small. Many participants were so sick that they needed hospitalization, which could have influenced results. Finally, it only studied changes within a year of infection; three to five years later, there may be different markers in the blood, said Seltzer. Patients’ immune systems may not be able to stay overactive indefinitely.

These features suggest potential interventions, wrote Wolfram Ruf of the Center for Thrombosis and Hemostasis in Germany, in a commentary that accompanied the report. Perhaps anti-inflammatory drugs would help. Anti-coagulants might reduce the risk of dangerous blood clots.

“Eventually, the hope is that some of these findings can translate into the clinic, but we are still a ways away from that,” said Peluso. “We need to keep up the momentum to get answers for the tens of millions of people with this disabling condition.”

Summer visitors driving to Yosemite National Park will soon find out, when the park moves to a reservation-only entry system, like movie theaters and theme parks.

Overwhelmed by last year’s crush of visitors, the popular park will also require advance booking of vehicles on spring and autumn weekends, according to a plan announced by the Park on Wednesday. Reservations will open at 8 a.m. on Jan. 5.

The plan is based on the past four years of experience, as well as public feedback and lessons learned from other national parks, said Superintendent Cicely Muldoon.

Reservations were required during the COVID pandemic, then again in 2022, from March 23 to Sept. 30, due to a number of construction projects that restricted access to some popular areas of the park that year.

The limits on visitors enhanced the wilderness experience, rather than detracting from it, she said.

“The people who were able to get reservations absolutely loved it,” experiencing giant sequoia groves, wilderness and waterfalls free of stress and congestion, said Muldoon. “It was a game-changing experience — how one would want to visit a national park.”

When the system was suspended last summer, chaos ensued, Muldoon said. Huge crowds caused such long waits to get into the park that some visitors were forced to turn back. Cars were parked illegally in traffic lanes, on grass and between rocks, with lines stretching on for hours. The havoc was compounded by deep Sierra snow and a shortened season, concentrating visitors into peak summer months.

“It was back to the bad old days,” said Muldoon. “It was really terrible. Parking was off-the-charts crazy.”

Walk-in visitors do not require a reservation, but for travelers who drive, reservations are required for entry on weekends from April 13 to June 30; every day from July 1 to Aug. 15; and on weekends from Aug. 16 to Oct. 27. They must be booked through the website Recreation.gov/timed-entry/10086745.

Visitors will pick from two types of reservations: Reservations valid for a full day, or reservations valid for entry any time after noon. Both reservation types — full day and afternoon — are valid for up to three consecutive days, including the arrival date.

There will still be opportunities for casual drop-ins. Reservations aren’t needed to enter the park after 4 p.m. – or before 5 a.m., if you’re an early bird.

Visitors with in-park lodging or campground reservations, wilderness or Half Dome permits, or who enter the park on buses or on commercial tours do not need a reservation.

Afternoon arrivals and additional full day reservations may be added one week in advance — for example, reservations for a Sept. 30 arrival date will be added on Sept. 23.

Reservations are also required to enter Yosemite on the weekends of Feb. 10-12, Feb. 17-19, and Feb. 24-26, during peak time for the “firefall,” a waterfall streaming down the face of El Capitan and illuminated by a February sunset. The firefall, which has become a massive draw for photographers, occurs in February when the setting sun hits Horsetail Fall at just the right angle. Campsites usually available on a first-come, first-served basis will also require reservations.

Several other national parks are taking a similar approach, such as Marin County’s Muir Woods, Arches National Park in Utah, Rocky Mountain National Park in Colorado, Acadia National Park in Maine and Glacier National Park in Montana.

The online reservation system has raised concerns that it will discourage visitors such as the low-income and historically marginalized communities that the Park Service is working hard to attract.

Many people don’t have a job or lifestyle that allows them to plan six months in advance for a vacation, say critics.

But Mark Rose, manager of the National Parks Conservation Association Sierra Nevada Program, commended Yosemite’s strategy, saying that all visitors to the park, “especially those from underrepresented communities, deserve a positive experience, not gridlock traffic.”

“We strongly support the return of Yosemite’s reservation system in 2024, particularly following a summer where no limitations at park gates led to frequent hours’ long traffic jams, Valley closures, and untold damage to natural and cultural resources,” he said. “Beyond 2024, we urge the Park Service to move once and for all towards a permanent reservation system.”

Yosemite is working with its nonprofit partners to publicize the reservation system in Spanish and do outreach in the Central Valley, said Muldoon.

“We need to find a system that is equitable,” she said. “We really want to expand that effort.”

The reservation requirement may enhance the experience for visitors, but it could mean less business for the shops and lodges that surround the park, according to the Yosemite Mariposa County Tourism Bureau.

Tony McDaniel of the Tourism Bureau said it plans to promote other activities in the region, such as visiting Gold Rush history.

“When tourism is slowed by the reservation system…people aren’t filling our hotels, and they’re also not supporting other small businesses,” he said. “Our businesses located outside of the park in Mariposa County are trying to basically make up an entire year’s worth of profit with generally just the summer periods. So when the park puts a reservation system in place, those businesses are left trying to adapt.”

“We’ll help people understand there’s more to see in Mariposa County than just in Yosemite,” he said.

Now — full of promise and peril — psychedelics are undergoing a makeover. Chemical neuroscientists, many based in Northern California, are redesigning the structures of psilocybin, ketamine, MDMA and other powerful drugs to concoct compounds that they hope will offer mental health benefits with fewer risks.

With advanced tech tools and a deepened understanding of brain chemistry, scientists say the new drugs might succeed where conventional therapies have failed, treating post-traumatic stress disorder, anxiety, depression, addiction and other devastating mental health problems.

“Our goal is to make medicines that are derived from psychedelics that are safer and gentler, more effective and more accessible,” said Matthew Baggott, former director of data science and engineering at Genentech, whose Palo Alto-based startup Tactogen has patented several novel MDMA, or “Ecstasy,” molecules that offer spiritual and personal insights with less heart-racing anxiety and euphoria.

At the new UC Davis Institute for Psychedelics and Neurotherapeutics, director David Olson is tweaking psychoactive drugs to spur neural growth and rewire the troubled brain without triggering hallucinations or adverse effects. His biotech startup, Delix Therapeutics, has built a portfolio of more than 2,000 non-hallucinogenic compounds.

Stanford University School of Medicine investigators Dr. Boris Heifets and Dr. Rob Malenka have pried apart MDMA’s therapeutic and addictive traits, distinguishing the different molecular pathways behind the drug’s sociability and abuse potential.

RELATED: Psychedelic drugs: Follow the money

“Can we deconstruct these drugs — basically, take them apart and put them back together — so that they have one of these effects and not the other?” said Heifets, assistant professor of anesthesiology, perioperative and pain medicine.

Separating the agony from ecstasy “would be more helpful and less harmful,” he said.

So far, researchers have managed to demonstrate such decoupling only in rodents. The research in people is embryonic, so we don’t yet know whether drugs can be purely therapeutic.

Compared to modern medicines, the classic psychedelics are elderly. MDMA, or “ecstasy,” was synthesized in 1912 when Woodrow Wilson was president. Swiss chemist Albert Hofmann isolated LSD from grain fungus in 1938 and psilocybin, found in “magic mushrooms,” in 1958. DMT was isolated from the root bark of a tree in 1946. Ketamine, an anesthetic, was made in 1962.

But therapeutic research slowed in the mid-1960s amid President Nixon’s “War on Drugs,” tightened regulations and disappointing clinical trials.

Psychedelic drugs have long been known to be among the most powerful substances to act on the human brain. Emerging science shows why: They stimulate a receptor in the brain known as 5-hydroxytryptamine 2A (5-HT2A), as well as other lesser known brain receptors. There is evidence that they can produce changes in brain architecture by spurring regrowth of damaged neural circuitry and new connections between synapses.

But there are major downsides. Some cause life-threatening heart problems or body overheating. Perception-distorting effects may make them distressing, even dangerous, for people with a predisposition to mental illness. Patients on anti-depressants such as Prozac also risk adverse reactions. Some of the drugs are hard to administer and persist longer than needed.

An off-duty Alaska Airlines pilot charged with trying to shut off the engines of a flight in October told investigators that he had been sleepless and dehydrated since he consumed psychedelic mushrooms about 48 hours before boarding. He had struggled with depression for months, he said.

“They have tremendous potential, but they’re very crude tools,” said Heifets.

Psychedelics are classified as Schedule I substances, illegal except under tightly regulated circumstances, so researchers have faced legal restrictions and professional stigma.

But now, with growing frustration over shortcomings of conventional therapies, there are incentives to innovate.

Private investment into psychedelic research and development has surged, supported by an FDA “breakthrough therapy” designation for clinical trials of psilocybin for depression in 2018. Next summer, the FDA is expected to approve MDMA as a treatment for PTSD, based on clinical trial results at UC San Francisco in a study by the San Jose-based Multidisciplinary Association for Psychedelic Studies.

Philanthropic, institutional and government funding of research has led to the creation of academic centers for psychedelic science across the country. In 2020, the Defense Advanced Research Projects Agency (DARPA) directed $27 million to a 30-person lab at the University of North Carolina at Chapel Hill, where professor Dr. Bryan Roth uses robots, computational chemistry and electron microscopy to identify thousands of new chemical structures.

More than 100 companies are focused on psychoactive drugs, according to patent attorney Graham Pechenik of the San Francisco-based Calyx Law.  Five years ago, only a few dozen patent applications had been submitted for psychoactive-related products, he said. Now his Psychedelic Alpha patent tracker counts more than 1,000.

“I really thought that psychedelics were going to just stay underground forever or maybe stay this weird area of academic research,” said Brom Rector of Empath Ventures, which invests in early stage psychedelic-focused companies. “Over the last few years, all that’s changed.”

Meanwhile, the cultural conversation around psychedelics has begun to shift. Oakland, San Francisco, Santa Cruz and Berkeley have decriminalized “natural” psychedelics. Gov. Gavin Newsom vetoed a bill that would have allowed personal possession of psychedelic mushrooms in California, asking lawmakers to send a version next year with therapeutic guidelines — suggesting that he might be more supportive of medicinal use than decriminalization.

Scientists say research needs to keep up. “The psychedelic landscape is moving very, very quickly. … People are starting to use them without the appropriate guardrails in place,” said Olson. “We still need to understand how they work.”

To make them safer, scientists enlist one of two strategies.

Some are modifying the chemical structures of existing drugs, such as swapping an oxygen atom for a carbon atom. Others are building new drugs from scratch, assembling them like Tinker Toys. They might select the components that are needed to promote neural growth, for instance, but delete those linked to hallucinations.

Updates are long overdue, said Rector.

Existing psychedelics “are the best drugs from almost 100 years ago — the Ford Model T of psychedelics,” he said. “I want to see what the Tesla Model S in psychedelics is going to be like.”