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.

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.”

But biotech startups, academic scientists and investors say that research into psychedelic drugs starts with a major advantage: These substances are already known to work.

The goal is simply to improve upon them – so they’re safer, more effective and faster-acting. Someday, perhaps, psychedelic-like drugs could treat mental illness for a fraction of what it costs to do therapy with conventional tools.

RELATED: New psychedelic-like drugs: All treatment, no trip?

Three drugs — MDMA, psilocybin, and ketamine — are the furthest along in clinical development for mental health disorders, according to Dr. Boris Heifets of the Stanford University School of Medicine.

Investors are already betting tens of millions of dollars, sensing the opportunity to replace drugs like Prozac, Zoloft and other selective serotonin reuptake inhibitors. Prescription sales for these depression treatments are estimated to be $50 billion a year globally, while the mental health market is worth about $100 billion in annual sales.

Venture-capital funds that are focused on early stage psychedelic companies include Empath Ventures in Los Angeles, Tabula Rasa Ventures in New York City; PsyMed Ventures in San Francisco.

“It’s now socially acceptable for a respected scientist to study psychedelics and run a clinical trial,” said Brom Rector of Empath Ventures. “And it’s acceptable for a serious venture capitalist to put money into a psychedelic company.”

Over 1,000 patent applications have been supported in this new field, according to patent attorney Graham Pechenik of San Francisco’s Calyx Law. According to his patent tracking website, more than 400 involve the drug psilocybin; 250, ketamine; 200, ibogaine; 200, LSD; 200, DMT, 150, MDMA, and 100 for a drug called 5-MeO-DMT. Because patent applications are only made public 18 months after submission, the real number is likely far higher, he added.

A recent report from Data Bridge Market Research projects that the global market for pharmaceutical psychedelics will reach $6.4 billion by 2030.

Some companies merely tinker with existing agents, aiming to fine-tune them. But others are developing entirely new chemical entities. Using computers, scientists model their structure. Then they send instructions overseas, usually to India, where the molecules are produced. Once returned to the U.S., they are tested with so-called screening assays to identify any promise.

Companies working with psychedelic drugs include:

• Arcadia Medicine, San Francisco
• Atai Life Sciences, Berlin, Germany
• Beckley Psytech, Oxford, England
• Bright Minds. New York City
• Compass Pathways, London, England
• Cybin, Toronto, Canada
• Delix Therapeutics, Boston
• Freedom Biosciences, San Francisco
• GH Research, Dublin, Ireland
• Gilgamesh Pharmaceuticals, New York City
• Mind Medicine, New York City
• Multidisciplinary Association for Psychedelic Studies, San Jose
• Reunion Neuroscience, Toronto, Ontario, Canada
• Tactogen, Palo Alto
• Usona Institute, Madison, WI
• Viridia Life Science, New York City

Born with a deadly blood disease, the Finlayson’s daughters — Ada, 9, and Lily, 12 — are the first patients on the West Coast to receive a new gene therapy offered by UCSF Benioff Children’s Hospital Oakland.

Already, Ada is already feeling better 10 weeks after receiving her stem cell transplant. Lily started treatment last week. Both have 90% chance of a permanent cure.

“It’s science, and it’s a miracle,” said their mother Alissa, sitting in the small yard of their guest home in downtown Oakland, far from their small mountain town of Kalispell, Montana.

The children were born with beta thalassemia, a common hereditary red blood cell diseases in China. Unable to create normal blood cells, they’ve needed six-hour-long blood transfusions every 21 days, an intense treatment that carries risk and requires constant monitoring.

Because Chinese orphanages can’t provide treatment, both girls were destined to live short lives.

Then the family found that UCSF’s Oakland hospital is one of three sites in the U.S. to offer the initial test of the therapy, Zynteglo. Now that Zynteglo is FDA approved, the hospital is among 15 in the nation authorized to provide care. Stanford’s Lucile Packard Children’s Hospital, Loma Linda University Children Hospital and Seattle Children’s Hospital will also offer the treatment.

The therapy is a one-time treatment that works by using an engineered virus to deliver a healthy gene into patient cells. It’s not the same as CRISPR, which uses gene editing to fix existing genes. That process is still under review and has not received FDA approval.

“The point of the treatment is to stop those transfusions,” said Dr. Mark Walters, a hematologist and director of the hospital’s Pediatric Blood and Marrow Transplant Program. Walters will follow the girls and other patients for 15 years to see if there are long-term complications, or if they remain free of disease and can be considered truly cured. Other patients are in the hospital’s pipeline.

Beta thalassemia is caused by a single mutation on the gene for hemoglobin, the protein in red blood cells that carries oxygen to tissues. Children develop life-threatening anemia. They can’t gain weight or grow properly.  They suffer organ damage.

By fixing the underlying genetic problem, the new treatment buoys hopes for an estimated 1,300 to 1,500 patients — and opens up the possibility of treating other simple inherited disorders.

Scientists say this approach will be a crucial part of 21st century medicine. An estimated 400 million people worldwide are affected by one of the 7,000 diseases caused by mutations in a single gene. ‌

“It’s incredibly exciting time, as we harness what we’ve learn about genes and then how to fix them,” said Walters.

“This is just one disease we’re treating with the gene therapy,” he said. “There are lots and lots of others to work on. All the lessons we’ve learned about genetics are coming to fruition.”

These customized treatments remain challenging to build and are profoundly expensive. Zynteglo, made by Massachusetts-based biotech company bluebird bio, costs $2.8 million for a single-use vial, making it one of the most expensive drugs in the world.

But money is saved by a lifetime without ongoing care, which can cost many millions of dollars.

Devout Christians, the Finlaysons married in their early 20s and soon bore two biological children in the picturesque 1800s-era town near Glacier National Park, with mountains, alpine trails and lakes filled with trout. Clint, 41, is an engineer; Alissa, 38, is a music teacher who homeschools their children.

Seeking to grow their family, they shared a dream of adoption. They agreed to welcome a child with any medical condition.

“It’s just something that you figure out,” said Alissa. “We have very strong faith that God is going to put the child in our path that he wants us to adopt.”

Charmed by Lily’s cherubic photo, they brought her home.  About a year later, they received a call asking if they would consider adopting a second girl, Ada, with the same medical condition. Their answer was a definitive “Yes.”

They’re now inseparable. Lily is quiet, thoughtful and strong. Ada is an impish ball of energy.

To keep them healthy, “it’s like a weight you put on,” said Clint. “But after awhile, you forget it’s there.”

When the couple learned of the promise of gene therapy, they rushed to put their names on the hospital’s wait list. Friends’ daughters, also adopted from China, had completed the clinical trial and were thriving.

The call came as Alissa was sitting on the family couch, teaching her brood. “I recognized the 510 area code,” she said. “I didn’t hesitate. I said: ‘Yes. When can we come?’ “

“We believe that God has paved a way for us to be here,” she said, pausing for the roar of a passing BART train. “We miss home, but we love how knowledgeable the people here are, and how they treat us as a family.”

Ada went first. From start to finish, the process took four months.

First, her stem cells were collected from her blood. Using a virus, healthy copies of the hemaglobin gene were inserted into these collected cells, then grown for three months.

Chemotherapy killed off the bad stem cells in her bone marrow to make room for the new healthy cells. Her hair fell out. The cells were infused into her body, and found their home in her marrow. They are now beginning to pump out normal hemoglobin.

The beauty of this approach is that patients don’t reject their own bone marrow. And there’s no risk of a dangerous complication caused when foreign cells attack the body’s own tissues.

“You just do the next thing, and the next thing leads you to something else,” said Clint. “Then eventually, holy cow, you’re on the other side of it.”

For the first time in her life, Ada needs no transfusions. While her hemoglobin levels won’t fully stabilize for a year, her spunk is emerging as the disease departs.

Lily’s treatment, delayed by a cell manufacturing error, has now started. It was a major disappointment, because the girls could not be treated together. And instead of staying in Oakland for four months, the family must be here for eight.

The Finlaysons also struggled to gain insurance coverage, and feared medical debt. After two months of daily phone calls with Aetna, coverage is now guaranteed.

“You feel these painful moments and you just want to give up sometimes,” said Alissa. “But we’re blessed to be here. We have an army of family, friends and our church praying for our entire family.”

Impatient with her family’s tale, Ada bounced over, announcing “This is boring to listen to!”

“I don’t really think the magnitude of this has hit them,” Alissa said, offering a hug. “They think getting cured is totally normal.”

During the early stages of her illness, she created complex visual interpretations of classical music, such as George Gershwin’s Rhapsody in Blue and Maurice Ravel’s Boléro. Then she shifted to painting even more abstract concepts, such as numbers.

A recent UC San Francisco-led study of brain scans of Adams and other patients with the deadly “frontotemporal” variety of dementia has revealed the underlying mechanism behind this mysterious shift in creative expression.

As the brain region responsible for language is dying, it activates the visual processing area that drives creativity, according to Dr. Bruce Miller, the senior author of the recent study, a collaboration of 27 scientists published in the journal JAMA Neurology.

“This is a way that the brain copes with an insult,” said Miller, director of the UCSF Memory and Aging Center. “It mobilizes whatever circuits are still available and untouched.”

Similar yet different changes may help explain the mood and behavioral shifts sometimes seen in patients who have had other brain injuries or illnesses, such as stroke or Alzheimer’s disease, he said.

The UCSF research also offers insights into the workings of the healthy brain, engaged in a constant dance — some circuits turning on and others turning off.

On Friday night, Adams’ story — which, uncannily, parallels a similar burst of creativity and mental decline in the composer Ravel a century earlier — will be told on stage at the San Francisco Conservatory of Music in a one-night performance of the play UnRavelled. The performance, produced by the Association for Frontotemporal Degeneration, will be followed by a 30-minute panel discussion on creativity and brain science by UCSF’s Miller and other experts.

“It is a very beautiful, sad story that captures the birth of something extraordinary,” said Miller.

Frontotemporal dementia (FTD), which affects about 60,000 Americans, is different from Alzheimer’s disease. It typically affects people younger — in their 50s and 60s — such as actor Bruce Willis. It doesn’t affect memory; rather, it changes behavior and language. It is incurable, and there are no approved therapies to slow or alter its course.

Scientists previously thought that neurodegenerative diseases hit the brain everywhere, at once. Now they know that they start in a very small and specific region of the brain, targeting certain cells. But over time, the damage spreads and is lethal.

Misfolded proteins build up in the frontal and temporal lobes, disrupting and eventually killing cells called von Economo neurons. This part of the brain does a lot of things — but its most important job is language and social behavior.

A small subset of patients with a specific variant of FTD show a burst of visual creativity as they decline — painting or making montages, pottery, sculpture, jewelry, quilts, even welding colorful insect-like creatures. It is not known why some patients develop creativity and others don’t.

Patients who were artists become more visually obsessed. But even people with no previous interest in art become engaged in their new hobby for many hours a day.

When healthy, UCSF patient Victor Wightman had no interest in art; he enjoyed running, swimming and basketball. But at age 48, a year before his FTD diagnosis, he began painting images of animals and cartoon characters in vivid, almost electric, colors.

Another patient, Jancy Chang, was a talented Santa Cruz artist and teacher. After retirement at age 52 due to declining language skills, her paintings became much bolder, wilder and more original.

A third, Dick Smith, became a constant walker as he declined. He wasn’t experienced in art, and was too restless to focus. But as he circled, caregivers handed him a paint brush. With each restless loop, his colors changed.

Such research can accelerate the search for therapeutics and improve caregiving, said Susan Dickinson, CEO of the Association for Frontotemporal Degeneration.

“Everything we learn about the fundamental aspects of what this disease is, and how it affects the brain, will help us design strategies to intervene, or even prevent, the disease process,” she said. “And it offer clues for ways to help families stay connected with the people they love, helping maintain the quality of life as long as possible.”

“Even if patients don’t become beautifully creative, like Anne Adams did,” Dickinson said, “are there ways to help them stay active and feel purposeful?”

The link between FTD and new artistic talent was first described by Miller in 2007 in the journal Brain. The new UCSF study, led by behavioral neurologist Dr. Adit Friedberg, sought to understand why.

The team analyzed the records of 689 FTD patients and identified 17, or 2.5%, who had experienced a burst in visual creativity at the start of their dementia. It compared the brain scans of these patients to matched patients who did not show increased creativity, as well as the brains of mentally healthy people.

The scans revealed that the region of the frontal cortex, responsible for language, had shrunk in visually creative patients, while areas in the back of the brain on the right side, devoted to visual and spatial processing, were more active.

In healthy people, these visual regions may be inhibited by the dominant frontal cortex, said Miller. But when damaged, creativity is released.

This shift seems to reflect “neuroplasticity” — the ability of the brain to form new connections or reorganize itself, the study concluded. It also found an enlargement in the area of the brain that involves movement of the right hand.

“When one part of the brain doesn’t work as well, other areas may be able to work better than they did before,” said Miller.”

Periodic brain scans at UCSF offered a remarkable glimpse of changes in Anne Adams, from her diagnosis in 1997 until her death in 2007.

Trained in physics and chemistry, she earned a PhD in cell biology while raising four children. She taught and did research at the University of British Columbia, then left her career to take care of an injured son. To pass the time, she turned to art. Her initial works were simple drawings and architectural watercolors.

“She was very bright, and she was also artistic,” said her widower Robert Adams, 83, a professor emeritus of math at the University of British Columbia.

Increasingly drawn to repetition and abstraction, her work turned more vibrant. In a rendering of the mathematical ratio pi, she mapped a vivid matrix of its first 1,471 digits.

Her most ambitious piece, which took three months, deconstructed Ravel’s famous song Boléro. The insistent, rhythmic plod of the music — all 340 bars — was transformed into symbols and colors. The A note was painted silver; A-flat, copper; B, leaf green; B-flat, metallic green, and so on.

Just like Boléro‘s melody, her symbols repeated and repeated. With each crescendo, the rectangles grew taller.

Scientists now suspect that in the late 1920s, when Ravel composed Boléro, he also suffered from FTD. A man of order and perfection, his behavior turned erratic. Within several years, he lost the ability to translate music from his mind into notes.

Soon Anne began to struggle to find words and add numbers. Her paintings grew increasingly symmetrical. Her final works, achieved when she was nearly mute, moved towards photographic realism.

“Painting was something she could do easily,” Adams said. “Every morning, she would come down and go into her office and paint,” eight hours a day.”

Tragically, the illness slowly claimed both Anne’s words and skills. But her drive to paint persisted.

“She got to the stage where she’d come down, sit down at her desk, with the paints in front of her,” said Robert Adams. “And she’d just look at them.”

“We were inspired by the natural system and wanted to mimic it,” said Weichen Wang, whose team published its success in the journal Science. “Maybe we can someday help patients to not only restore motor function, but also restore their sensations.”

Much faster, larger and more sophisticated circuitry is needed before so-called “e-skin” holds promise for people.

But, in a milestone, the device showed remarkable success in a lab rat. When researchers pressed the rat’s e-skin and sent electronic pulses to its brain, the animal responded by twitching its leg.

Scientists have long dreamed of building prosthetic limbs that not only restore movement but also provide perception – sensing pressure, temperature and vibration, for instance — to help restore a more normal quality of life. Skin damage and amputation cause a massive disruption in the loop of perception and movement, so even simple tasks like feeling or grasping an object are challenging.

“If you pick up a glass of beer and you can’t sense that it’s not cold, then you won’t get the right taste,” said Ravinder Dahiya, professor of electrical and computer engineering at Northeastern University in Boston, who is also studying the use of flexible electronics to develop artificial skin.

Electronic skin also could be used to clad robots so they feel sensations in the same way that humans do. This is critical to the safety of industries where robots and humans have physical interactions, such as passing tools on a manufacturing floor.

But the sensation of touch is complicated. Human skin has millions of receptors that sense when they are poked or pressed, squeezed or scalded. They react by sending electrical pulses to the brain, through nerves. The brain responds by sending information back, telling muscles to move.

And biological skin is soft and can stretch, repeatedly, for many decades.

The Stanford team, led by chemical engineering professor Zhenan Bao, has been working on e-skin designs for several years. But an earlier effort used rigid electronics and 30 volts of power, which requires 10 batteries and isn’t safe. And it wasn’t able to endure continuous stretching without losing its electrical properties.

“The hurdle was not so much finding mechanisms to mimic the remarkable sensory abilities of human touch, but bringing them together using only skin-like materials,” said Bao, in a statement.

The new e-skin is innovative because it uses networked layers of stretchable organic transistors that perceive and transmit electrical signals. When sandwiched, the layers are only about 25 to 50 microns thick – as thin as a sheet of paper, similar to skin.

Its networks act as sensors, engineered to sense pressure, temperature, strain, and chemicals. They turn this sensory information into an electrical pulse.

And the e-skin runs on only 5 volts of electricity.

To test the system, the Stanford team implanted it into a live rat. When the rat’s e-skin was touched, a pulse was transmitted by a wire to the rat’s brain – specifically, an area called the somatosensory cortex, which is responsible for processing physical sensations.

The rat’s brain responded by sending an electrical signal down to its leg. This was done using a device that amplifies and transmits signals from the brain to muscles, mimicking connections in the nervous system called synapses.

The rat’s leg twitched. Significantly, its movement corresponded to varying levels of pressure, said Wang, an engineering PhD and first author on the new paper. For example, the team could increase the leg’s movement by pushing the e-skin harder, which boosted the signal’s frequency and the transistor’s output.

If tested in humans, the device would not require implantation of a wire to send sensory information to the brain. Rather, the team envisions using wireless communication between e-skin and an electrical stimulator located next to a nerve.

Joe McTernan of the American Orthotic and Prosthetic Association said such research encourages technological advancements that could someday provide real-time biofeedback for people who have lost limbs.

“Although this skin technology is fairly new, there has been significant research and development in recent years that have focused on creating a positive tactile experience for the patient,” he said.

The Stanford team’s closed-loop system — from sensation to muscle movement — is “very exciting…very much a proof of concept,” bioelectronics expert Alejandro Carnicer-Lombarte of University of Cambridge told the journal Nature.

In the field of artificial prosthetics, most researchers tend to work on individual components, he said. “Combining those things, in sequence, is not trivial.”

Dahiya applauded the team’s success in building flexible electronics and then making them work. “That’s where they’ve done a nice job,” he said.

But he said there’s still a missing piece of the puzzle: creating memory. Unlike Stanford’s e-skin, human skin learns how an object feels, then can anticipate it.

There’s another challenge: The transmission of signals is currently too slow to be useful. The flow of information through the team’s flexible carbon-based transistors is sluggish compared to more traditional silicon-based transistors, he said.

Such a delay “will not allow us to get a real feeling,” Dahiya said. “And without real feeling, then you have a practical bottleneck.”

At Stanford, the next step is to pack more and different sensors into the e-skin, to more closely replicate the many sensations felt by the human hand, said Wang.

“We’re scaling up,” he said. “It will be more advanced.

“The whole field is under development,” he said. “It will take many more generations of developments to realize our target.”

Her plug-in hybrid Chevy Volt, linked to the house by long extension cords, powered her family’s favorite lamp, as well as the refrigerator, internet and furnace. It charged the batteries that run her phone, laptop, electric blanket, camp light, flashlights, power tools and a comfy heating pad that wraps around her shoulders.

“It’s turned outages into slight inconveniences, rather than the hardships they used to be,” said Snyder, a 62-year-old who radiates practicality. Her family’s scenic Santa Cruz Mountains home is more than a dozen miles away from the comfort of the nearest town — and lost PG&E power 13 times this winter, once for eight days and another for six days.

Her homespun setup is a preview of what may soon be easily available to many Californians: EVs that are equipped not just to receive power, but also to deliver it.

A new bill, proposed last month by State Sen. Nancy Skinner, D-Berkeley, would require that all new electric vehicles in California are equipped with so-called “bidirectional” charging by 2027. Passage of SB 233, which will be heard tomorrow before the Senate Energy Committee and on April 25 before the Senate Transportation Committee, could make two-way charging the norm, not a special feature.

“EVs are energy storage on wheels. Why waste that battery, given how few miles most people use the vehicle in any given day?” said Skinner, whose initiative was a major focus at this week’s California Climate Policy Summit in Sacramento. “But we need to make it as easy as possible.”

Electric car batteries can hold approximately 60 kilowatt hours of energy, enough to provide backup power to an average U.S. household for two to three days — or far longer, if the home’s electrical use is conserved.

Skinner’s effort comes as the Biden administration sets the stage for a major national expansion of EV use. On Wednesday, the EPA proposed strict new limits on emissions that would require as many as two-thirds of new vehicles sold in the U.S. to be electric by 2032. That’s a nearly tenfold increase over current electric vehicle sales.

California is already far ahead. Last year, 16.3% of new vehicle sales in the state were electric vehicles, far outpacing the nationwide rate of 5.8%. California is projected to have at least 8 million EVs on the road by 2030.

Meanwhile, state residents face a growing threat of rolling blackouts as the power grid is overtaxed during periods of peak demand, such as during the heat wave on Sept. 6, 2022, that brought outages to Alameda and Palo Alto. This winter’s parade of atmospheric rivers also caused widespread power losses.

By harnessing the untapped battery storage capacity of electric vehicles, California can address three challenges at once: cleaning up the air while keeping the lights on and reducing energy bills, according to Ellie Cohen, CEO of The Climate Center, based in Santa Rosa.

As the state moves into an all-electric future, “bidirectional vehicles can play a huge role to get to where we need to go, faster,” she said.

California’s cars will have 60,000 megawatts of stored energy in batteries by 2030, according to Siva Gunda of the California Energy Commission. If only 10% of that could be returned to the grid, “we can get through what we went through last year without turning on the backup generators,” said Gunda.

Now most EVs have one-direction charging. Power is taken from the grid and charges the car’s battery.

Only the Nissan Leaf, Kia EV-6, Hyundai Ioniq 5 and Ford F-150 Lightning offer built-in “bidirectionality” to homes or the grid. Tesla recently announced that its vehicles will be “bidirectional” by 2025.

PG&E strongly supports the move toward bidirectional vehicles, saying it is preparing the grid. “It represents a new path. We want to lead the country in reliability, resiliency and reduced emissions,” said Aaron August, vice president of PG&E’s Utility Partnerships and Innovation

But the state is not yet ready for immediate widespread adoption, said PG&E and other experts.

Procedural and regulatory changes are required before EV backup power becomes an everyday thing, said Jackie Piero of the Belmont-based company The Mobility House, which provides the technology that lets electric AC Transit buses power the Oakland Public Library during emergencies. “Smart meters” or other tools would be needed during outages to ensure that utility workers aren’t injured by a car’s energy, she said.

Standards, now in development, would help the grid protect itself, said PG&E’s August. Standards are also being designed to align how chargers talk to the car. For instance, Nissan and Ford currently use different strategies, requiring consumers to purchase different equipment.

Until then, resourceful “hackers” like Snyder have built their own bidirectional systems. A stay-at-home mom with a background in math and computer science, she loves nature, dancing, 5,000-piece jigsaw puzzles — and self-sufficiency. A neatly organized cart in her home holds eight 40-volt batteries, six 18-volt batteries, two 40-volt inverters and two 18-volt inverters.

The centerpiece of her EV setup is a 1500-watt inverter, which converts the car battery’s DC power to the AC power needed by her home. Bright blue, the inverter cost $220 and lives in the trunk of her car, a 2017 model.

The inverter hooks up, via cables, to the car’s 12-volt battery, which is propelled by the car’s big battery. It also connects to two long extension cords, 15 amps each, which are routed down the driveway to her home. One cord runs through a kitchen window to a power strip, supporting appliances and recharging batteries. The other cord runs into a closet, supporting the furnace and internet router.

“They’re just consumer electronics,” she said. “It only takes about five minutes. It’s easy.”

She doesn’t want the car to think it’s not really going anyplace. So she fools it. To keep it from automatically turning off, she enlists what she calls “the rubber band trick,” using three blue rubber bands around the gearshift button to hold it in place.

Snyder’s effort reveals the commitment of Californians to create greater reliability in an all-electric world, said Kurt Johnson of the Climate Center.

But simplicity is essential, he said, for many more residents to reap the potential of this approach.

“I want to live in a world where, if the grid needs power when I get home, I just plug in my car,” he said.

The success, announced by Japanese researchers last month, has not yet been tried on people.

But scientists at two Bay Area startups, as well as a company in New York City and another in Japan, are striving to move the mouse research into humans, and rewrite the rules of reproduction by making sex cells in a lab. If successful in people, the technique would allow the creation of an egg cell from blood or a tiny sliver of a man or woman’s skin.

So far, the research has focused on making egg cells, which would enable male-male reproduction. Creating sperm for female-female reproduction is a tougher scientific challenge.

“Even the remote possibility of same-sex couples creating a baby without a donor is extraordinary and exciting,” said Drew Lloyd, board president of the Bay Area Municipal Elections Committee, which advocates for the civil rights of LGBTQ people. “I’ve learned not to put limits on what’s possible.”

Both Bay Area companies are secretive about the progress of their research and would not consent to interviews. The Berkeley-based startup Conception, with 34 employees and at least $20 million in private funding, seeks to create human eggs using stem cells from human blood samples. The other company, San Francisco’s Ivy Natal, aims to build eggs with a skin biopsy.

The new research, described by Katsuhiko Hayashi of Osaka University in the March 15 issue of the journal Nature, marks a milestone in reproductive biology.

The Japanese team guided stem cells from a male mouse to form eggs, which were fertilized by another male mouse. The two mice conceived seven pups who were healthy and fertile, eventually conceiving babies of their own.

But the project’s success rate was extremely low. About 30% of the male mouse’s stem cells matured into eggs, and 40% of those eggs were successfully fertilized to create embryos. The embryos were transferred to a surrogate female mouse to gestate, but only 1% — 7 out of 630 — were born alive.

Experts said it is not yet known whether the strategy would work in humans.

“Mice aren’t people,” said Hank Greely, director of the Center for Law and the Biosciences at Stanford University. “And it’s a complicated method.”

UC San Francisco developmental biologists Jonathan Bayer and Diana Laird agreed, writing “we have much to learn before we use cultured stem cells to make human eggs in a dish,” in an article that accompanied the Nature paper.

The technique, called in vitro gametogenesis or IVG, builds on the Nobel Prize-winning work of Dr. Shinya Yamanaka, a biologist at Japan’s Kyoto University who is also affiliated with San Francisco’s Gladstone Institute. In 2007, Yamanaka described how to create stem cells by reprogramming skin cells, turning them into “induced pluripotent stem cells,” or iPSCs. These iPSCs can be coaxed into becoming nearly any cell type in the human body, from brain to liver — and perhaps, someday, human egg or sperm.

The latest work was technically complex and required many steps. First, the team took skin cells from the tail of an adult male mouse. Then it reprogrammed these skin cells to become stem cells.

The biggest challenge was converting these stem cells from male to female. Because the production of mature eggs requires two copies of the X chromosome, the authors devised a way to find rare male stem cells that jettison their Y chromosome and then duplicate their X chromosome.

Once chromosomally female, these cells were biochemically nudged to turn into immature eggs.

The team tried, but failed, to make sperm from female cells. So two female mice could not conceive together. That’s because there’s not yet a successful technique for converting a cell with two X chromosomes into a Y chromosome — and without a Y chromosome, no sperm can be made.

In 2017, researchers in China created healthy mice with two mothers, but it involved a tremendous amount of gene editing with CRISPR, making it impractical to use for anything other than research. They also made mice with two dads, but the offspring quickly died.

But the breakthrough opens up exciting new avenues in reproductive biology and fertility research.

For instance, it could be used to rapidly produce inbred strains of identical mice, useful for laboratory experiments. It also offers a strategy to propagate endangered mammals from a single male.

It could also make replacement eggs for older women to have children, as well as couples who are infertile due to congenital problems, an accident, disease or treatment such as chemotherapy. 

And it would offer same-sex or transgender couples the chance to have their own biological children. Currently such couples must use the eggs or sperm from one person, and the eggs or sperm from a donor.

Adoptive parent Johnny Symons, professor in the School of Cinema at San Francisco State University whose documentary film Daddy & Papa focuses on the experience of gay men raising children through adoption and surrogacy, called family-building “an incredibly personal decision.”

“Having biological families has been least accessible to us,” he said. “This technology stands to be a real breakthrough in terms of providing options for people who want that.”

“If the technology advances, it could really change societal perceptions of gay men as parents, and potentially legitimize us in a new way,” said Symons. “There’s something very powerful and undeniable about physical resemblance. … It makes it harder for people who oppose us to deny us political rights or equal social standards.”

But there’s a darker side to making sex cells in the lab, said Greely, author of the 2016 book, “The End of Sex and the Future of Human Reproduction.”

“If this worked,” he said, “you could make eggs from sperm from 8-year-olds. You could make eggs from sperm from fetal remains. You could make eggs from sperm from somebody who has been dead for years, but whose cells were frozen. That gets a little weird.”

Someday, perhaps, it may be possible to create both eggs and sperm from the same person, creating what Greely calls a “unibaby.”  “You’re pregnant — by yourself,” he said. “I can’t imagine a good reason to do this.”

Even if the technique works in humans, it must first be proven safe, experts agree. Created through genetic manipulation, embryos may have hidden defects. There must be wider societal debate and regulatory oversight.

The next step is to test the technique in monkeys or chimpanzees.

Fertility experts, such as the American Society for Reproductive Medicine’s Research Institute, think it’s on the horizon.

New @Conception lab building coming together nicely!

It will meaningfully expand our research capabilities – ready in September. pic.twitter.com/7hetZeSika

— Matt Krisiloff (@mattkrisiloff) May 17, 2022

“If we can do this properly and safely and we can bring the cost down to being something accessible for everyone,” said Conception CEO Matt Krisiloff in a company video, “I really think there’s a possibility that this could become the default way people choose to have children.”

All three of the Bay Area’s airports are deploying new facial recognition technology, called Simplified Arrival, to screen incoming international passengers and testing it in San Jose to track some departing passengers too. It’s catching imposters and processing travelers more efficiently — but also raising privacy concerns.

“You get instant verification,” said James Hutton of U.S. Customs and Border Protection on a recent morning as hordes of bleary-eyed travelers streamed through San Francisco International Airport’s immigration control booths and paused for a snapshot.

“The camera does immediate identification,” he said, “telling the customs officer that, ‘This is the person that’s in front of me.’ “

The old approach we’ve long relied on — passport scanning and stamping — has vanished.

Instead, in a major overhaul of its strategy of processing travelers, government officials have installed cameras next to customs officers at all 238 international airports, 13 seaports and every pedestrian and bus processing facility along the nation’s northern and southern land borders. The new technology was introduced at Bay Area airports in 2020 and completed at all ports of entry nationwide last June.

TSA agents are testing similar devices for departing flights at some security check-in lines at San Jose International Airport and others — a “curb to gate” approach that uses the passenger’s face as a boarding pass.

“Your face is matched to the document that’s tied to your reservation,” easing the process of boarding passengers, said Hutton. “If we can verify that the person who went through TSA screening is the same person at the gate, you would never have to take your passport out of your pocket.”

It’s a far cry from the instantaneous-everywhere facial recognition portrayed in many popular TV crime shows, but biometric technology, which uses an individual’s unique physical traits to verify their identity, is increasingly used by private businesses and law enforcement.

Facial recognition is already a familiar part of smartphones, supplanting passwords. Most banks use “FaceID” to let customers securely log onto mobile banking apps. Target, Walmart and Lowe’s are experimenting with facial recognition to combat shoplifting and fraud, identifying known thieves.

At the nation’s borders, cameras started replacing self-serve passport kiosks in 2019 after a Congressional mandate, funded in 2016, directed the Department of Homeland Security to record the entry and exit of all foreign nationals. The effort, first tested at pedestrian crossing lanes in San Ysidro, is intended to prevent terrorism and find people who overstay their visas.

The pandemic accelerated the technology’s adoption, offering a “touchless” way to process passengers. Officials don’t have to scan a passport or clean a kiosk.

“This approach makes sense from a national security perspective,” said Stephen Flynn, founding director of the Boston-based Global Resilience Institute at Northeastern University.

“Border control efforts at ports of entry have always been a needle-in-the-haystack challenge, given the volume, velocity and variety of people, conveyances and goods moving through the world’s airports, seaports and border crossings.”

But civil liberties and digital privacy groups said the technology represents a fundamental threat to privacy.

“We see this continual expansion of facial recognition into more and more areas of our lives. And we are giving in to it with the promise that it somehow will make our experience more convenient,” said Albert Fox Cahn, executive director of the New York-based Surveillance Technology Oversight Project.

“Once you have someone’s biometric information, you have it for life,” he said. “You can change your credit card number. You can change your Social Security number. But you can never change your face. And so even if a program is only tracking our faces for one purpose today, it’s creating the biometric infrastructure to track it — however agencies may want to — in future years.”

Compared to fingerprinting, face-recognition technology poses a greater potential for growth into spy tools, critics say. That’s because it can be used for surveillance through public video cameras — mapping a person’s movement without their knowledge or consent.

Studies also suggest the technology is racially biased, with error rates rising significantly when applied to people of color, according to Jay Stanley, senior policy analyst with the ACLU Speech, Privacy, and Technology Project.

How does the new system work?

When entering the U.S. by plane and arriving at a Customs booth, a camera photographs your face. Then a computer checks that photo against all the images in a photo “gallery” of everyone else on your incoming flight. That’s possible because airlines are required to submit a list of passengers — and your fellow travelers already have submitted their photo to the U.S. government, either on a passport or a visa.

If your new photo matches your database photo, you don’t have to hand over your passport. The National Institute of Standards and Technology recently found that facial biometrics are nearly 99% accurate.

“That allows your officer to focus on questions: ‘Why are you coming into the United States? What’s the purpose of your trip? How long are you staying?’ ” said Hutton. “That interview doesn’t get supplanted, but it makes the officer more efficient.”

If you want your passport stamped, you can still request it. But most passengers are directed to an online site to get a copy of their arrival record.

The line-skipping system Global Entry also uses facial comparison technology.

If your photos don’t match, the system reverts to the traditional process: Officials look at your face, ask you to swipe your passport and may require that you submit fingerprints. They may ask tougher questions: “Where did you go to school? What was your school mascot?”

Passport photos are almost impossible to manipulate because images are stored in a chip. Already the system has stopped around 1,800 “impostors” — someone using a stolen, borrowed or counterfeit passport — from entering the country, according to Hutton.

After scanning at entry, photos of U.S. citizens are deleted within 12 hours. Photos of foreign nationals are permanently stored in a secure U.S. Department of Homeland Security system.

Americans can opt out, asking an agent to verify their identity the original way. There are exemptions for minors under age 14 and elders over age 80.

But every foreign national is required to participate. They may also be asked for fingerprints if they’ve never entered the U.S. before.

In the future, there may be no need to pose for a photo. Instead, your image may be taken soon after passengers get off the plane or boat, further streamlining the process, said Hutton.

“The ultimate vision is that there are cameras in the hallway,” said Hutton. “As you walk up, cameras would take a photo that says, ‘Oh, yes, that’s Ryan, coming back from Narita, Japan.’ “