Citizen Cartwright

Good news: World’s first personalized gene editing

On this good-news Friday, I’d like to give you this link to our edition of Fix the News and focus my summary here on the world’s first personalized gene editing treatment.

There are 350 million people worldwide with rare diseases, most of which are genetic, says The Associated Press.

And while researchers have developed gene-editing therapies for illnesses that affect millions of people with common genetic mutations, like sickle cell disease, millions of others have genetic diseases with unique mutations that need personalized therapy, says The Wall Street Journal.

KJ Muldoon was a week old when he was diagnosed with a rare genetic disorder, CPS1 deficiency, that affects just one in 1.3 million babies.

Now nine and a half months old, he's the first patient of any age to have a custom gene-editing treatment, The New York Times reports. He's received an infusion made just for him and designed to fix his precise mutation.

The investigators who led the effort to save KJ presented their work Thursday at the annual meeting of the American Society of Gene & Cell Therapy and are publishing it in the New England Journal of Medicine.

The implications of the treatment go far beyond treating KJ, says Dr. Peter Marks, who was the Food and Drug Administration official overseeing gene-therapy regulation until he recently resigned over disagreements with Robert F. Kennedy Jr., secretary of health and human services. 

More than 30 million people in the United States have one of more than 7,000 rare genetic diseases, and most are so rare that no company is willing to spend years developing a gene therapy that so few people would need.

But KJ’s treatment — which built on decades of federally funded research — offers a new way for companies to develop personalized treatments without going through years of expensive development and testing.

Illnesses like KJ’s are the result of a single mutation: an incorrect DNA letter among the three billion in the human genome. 

Correcting it requires pinpoint targeting called base editing. The treatment is wrapped in fatty lipid molecules to protect it from degradation in the blood on its way to the liver, where the edit will be made. Inside the lipids are instructions that tell the cells to produce an enzyme that edits the gene. They also carry a molecular GPS — CRISPR — altered to crawl along a person’s DNA until it finds the exact DNA letter that needs to be changed.

While KJ’s treatment was customized so CRISPR found just his mutation, the same kind of method could be adapted and used over and over to fix mutations in other places on a person’s DNA. Only the CRISPR instructions leading the editor to the spot on the DNA with the mutation would need to be changed. 

Treatments would be cheaper, “by an order of magnitude,” says Dr. Marks. He wrote an editorial accompanying the research paper and says the method “is, to me, one of the most potentially transformational technologies out there.” 

It eventually also could be used for more common genetic disorders such as sickle cell disease, cystic fibrosis, Huntington’s disease and muscular dystrophy.

Dozens of researchers put everything aside for months to work on KJ’s treatment, says the Times. 

David Liu of Harvard, whose lab invented the gene-editing method used to fix KJ’s mutation, says the speed was “astounding. These steps traditionally take the better part of a decade, if not longer.”

The success in treating KJ “is a triumph for the American peoples’ investment in biomedical research,” says Dr. Fyodor Urnov of the University of California at Berkeley.

The work began decades ago with federal funding for basic research on bacterial immune systems. That led eventually, with more federal funding, to the discovery of CRISPR. Federal funding for sequencing the human genome made it possible to identify KJ’s mutation. Federal funding supported Dr. Liu’s lab and its editing discovery. A federal program to study gene editing supported other research. Federally funded work led to an understanding of KJ’s disease.

“I don’t think this could have happened in any country other than the U.S.,” Dr. Urnov says. And “we all said to each other, ‘This is the most significant thing we have ever done.’”

Results of lawmakers’ all-nighters on ‘big, beautiful bill’

I’d love to be able to give you details of the legislation approved Wednesday as three House committees advanced their parts of the bill.

 

But with a gigantic bill like this — intended to make spending cuts to offset the costs of making President Trump’s 2017 tax cuts permanent — it’s routine that important details only emerge after Congress has passed the bill and the president has signed it.

 

There’s also this dynamic: 

 

"The House Energy and Commerce Committee was 16 hours into a nearly 27-hour markup [session to change and approve the bill] when it became clear that top Republicans on the panel weren’t clear on what key Medicaid provisions in the legislation they were actively debating would actually do,” Politico says.

 

The best summary of what’s in the bill that I can find continues to be this one from The Associated Press, published before the three committees finished their work.

 

The legislative package combining all the House committees' work is to be put together by the House Budget Committee on Friday.

 

Here are some details on Energy and Commerce’s health care piece of the bill, from Politico.

 

Here is a rundown on the House Agriculture Committee’s approval of $300 billion in nutrition spending cuts, also from Politico.

Good news on malaria prevention, brain microrobots, violets for a landfill

As usual, I hope you’ll have time to scan the many items of good news that are free in our Fix the News edition for this week.

Among the items behind the paywall:

— Insecticide-treated malaria nets have helped prevent more than 2 billion cases and nearly 13 million deaths since 2000, says the World Health Organization. 

— The French startup Robeauté is developing microrobots the size of a grain of rice that can navigate inside the brain, delivering targeted treatments and collecting samples without invasive surgery, reports the online publication EU-Startups.com. 

— Staten Island's Freshkills Park, once the world's largest landfill, is planting 50,000 native violets to attract monarch butterflies and bees, says SILive.com. 

Responding to difficult times

Over the years, I’ve mentioned various Buddhist resources for living this human experience, but I don’t think I’ve mentioned Tara Brach. I’ve been listening to Brach's podcasts for about ten years. She tells corny jokes, but I’ve found her very helpful.

Brach is a PhD clinical psychologist, and I’ve seen her on webinars training psychotherapists. She founded the Insight Meditation Community of Washington, D.C. And she’s the author of four books: "Radical Acceptance," "True Refuge," "Radical Compassion" and "Trusting the Gold." Her website says her podcast is downloaded more than 2.5 million times each month.  

In what I think is one of her best podcasts, she explores:

— The roots of tyranny and fear: ways unprocessed fear fuels aggression, domination and the rise of authoritarianism

— The power of belonging: how remembering our interconnectedness can empower resistance against oppression

— Inner freedom as a path to outer change: ways mindfulness and heart-centered practices dismantle fear and awaken courage

— The role of the "spiritual warrior": cultivating presence, compassion, and truth to stand against inner and outer oppression

— Taking action from love, not fear: ways small, heartfelt acts contribute to collective healing and justice

Trump’s speech to Congress

“President Trump, in his address to Congress Tuesday, celebrated the whirlwind of changes he has brought to the federal government. His success from this point on will depend largely on whether Americans believe the unease caused by his speedy actions — an unsettled stock market, a trade war with allies and uncertainty over the extent of federal job and spending cuts — will lead to the American renewal he promised,” says The Wall Street Journal.

 

Much of the 100-minute speech — the longest presidential address to Congress in modern history — “was filled with grievances about his treatment by Democrats and exaggerations about his accomplishments,” says The New York Times.

 

AP says the speech “added up to a defiant sales pitch for the policies that Trump promised during his campaign and leaned into during his first weeks back in office. Trump pledged to keep delivering sweeping change to rescue the nation from what he described as destruction and mistakes left by his predecessor. He seldom addressed his comments directly to the American people, who are trying to keep up with the recent upheaval, while repeatedly needling the Democratic lawmakers seated before him.”

 

Republicans chanted “USA! USA!” as Trump stepped to the lectern.

 

Rep. Al Green, D-Texas, who pushed to impeach Trump dating to his previous term in office, stood and shook his cane toward the president in the opening minutes of his speech and subsequently was removed from the chamber.

 

Some Democrats held black signs that read “save Medicaid,” “protect veterans,” “Musk steals” and “false."

 

Michigan Sen. Elissa Slotkin, who delivered the Democratic response after Trump’s speech, said “America wants change, but there’s a responsible way to make change and a reckless way, and we can make that change without forgetting who we are as a country and as a democracy.”

 

Here is reaction to the speech from experts at the Atlantic Council.

 

My thanks to my husband for compiling fact checks of Trump's speech:

 

AP

 

NYTimes

 

Washington Post

 

PolitiFact

 

ABC News

 

CBS News

 

NBC News

 

NPR

 

CNN

 

BBC News

How Musk’s businesses benefit from government shrinkage

President Trump and Elon Musk took questions from reporters in the Oval Office on Tuesday, and Trump signed an order directing federal agencies to work closely with Musk's effort to shrink the federal workforce.

The order sets forth rules requiring government agencies to hire no more than one employee for every four workers who leave, and it compels agencies to work with Musk's team to identify large-scale reductions in force and determine which agency components can be eliminated outright, Reuters reports.

 

“Trump resisted the suggestion by Democrats and other critics that Musk's role presents a conflict of interest,” Reuters says.

“If we thought that, we would not let him do that segment or look in that area, if we thought there was a lack of transparency or a conflict of interest,” said Trump.

 

Meanwhile, a New York Times article by two reporters who’ve spent the past year investigating Musk’s business with the federal government says many of the federal employees who’ve been pushed out were leading investigations, enforcement matters or lawsuits pending against Musk’s companies.

 

At least 11 federal agencies that have been affected by those moves have more than 32 continuing investigations, pending complaints or enforcement actions into Musk’s six companies, according to the Times.

 

Among them:

 

— Federal Aviation Administration fines of Musk’s SpaceX rocket company, for safety violations

 

— Securities and Exchange Commission lawsuit pressing Musk to pay the federal government perhaps as much as $150 million, accusing him of having violated federal securities law

 

— The National Labor Relations Board, an independent watchdog agency for workers’ rights, has 24 investigations into Musk’s companies

 

— At the Consumer Financial Protection Bureau, a public database shows hundreds of complaints about Musk's electric car company Tesla, mostly about debt collection or loan problems. The agency also would have regulated Musk’s new efforts to bring a payments service to X.

 

None of the investigations or lawsuits involving Musk and his companies, at least so far, have formally been dropped since the start of the new administration, according to more than a dozen current and former federal officials interviewed by the Times.

 

And the Times found no evidence that Musk directly ordered that an investigation into one of his companies be shut down or stalled.

“The shifts at the agencies in many cases reflect changes in national priorities that come with a president who has long complained that government regulation has been too aggressive, a view widely held in the business community,” says the Times.

“But the upheaval at federal agencies represents one of the first tests of a wide range of conflicts of interest Mr. Musk has brought to the White House, including 100 contracts with 17 federal agencies,” the Times says.

 

Musk controls Tesla, which is publicly traded. He's the founder of SpaceX; the artificial intelligence start-up xAI; the Boring Company, a tunneling venture; and Neuralink, which is developing brain computer implants. All of those are private companies. Musk also owns the social media platform X, formerly Twitter.

 

Musk’s companies secured $13 billion in contracts over the past five years, making SpaceX, which collects most of that money, one of the largest government contractors, the Times says. And there's already talk in the Trump administration of expanding these deals, especially at the Air Force.

 

On Monday, Trump fired the head of the Office of Government Ethics, an independent agency. The office had pending requests to investigate Musk based on allegations raised by Democrats in Congress last week that Musk’s role as a federal government official creates an unavoidable conflict of interest.

The letter from 12 House Democrats said, “The American people deserve assurances that no individual, regardless of stature, is permitted to influence policy for personal gain.”

Thank you, Jimmy Carter

Today is the national day of mourning for the former president.

 

It’s been very touching for me to work on this blog in the middle of the night while watching BBC News’ live coverage of people filing past Carter’s casket as he lies in state at the U.S. Capitol.

 

In the BBC audio that’s looping are comments by Carter’s grandson, Jason, who talks about Carter’s “foundational respect for human beings” and his value of democracy and common humanity in pursuit of shared goals. 

 

The lying in state ends at 7 a.m., and the national funeral service at the Washington National Cathedral is scheduled to begin at 10 a.m. 

 

President Biden is to delivery the eulogy. All of the living presidents are expected to attend.

 

“President Jimmy Carter had no idea what he was going to do next when he delivered his farewell address to the nation in January 1981,” says The New York Times. "Defeated after a single term by Ronald Reagan, he simply told Americans that he would leave the White House and 'take up once more the only title in our democracy superior to that of president — the title of citizen.’”

 

“There is little question among historians that Citizen Carter carved a new mold for life after the Oval Office and that his post-presidency was the most consequential in modern history,” the Times says.

 

A Times editorial published when Carter died on Dec. 29 is headlined, “America needs more Jimmy Carters.”

 

“Up to now, Jimmy Carter, who died on Sunday at age 100 in Plains, Ga., has been judged to be a middle-of-the-pack president, his one term in office remembered for circumstances and events that simply overwhelmed him: the seizure in Iran of 52 American hostages, the bungled attempt to rescue them, the gasoline lines, inflation, the Soviet invasion of Afghanistan.

 

“Yet he is also considered one of America’s greatest ex-presidents, for using the residual star power of his office to help his successors and his country as a peacemaker, backstage diplomat, human rights champion, monitor of free elections and advocate for the homeless while finding time to write poetry and, by his own example, providing the best possible case for traditional religious values.

 

“In 2002, having been nominated many times for the Nobel Peace Prize, Mr. Carter finally won it for his 'vital contribution' to the Camp David agreement, which set the stage for peace between Israel and Egypt, as well as for his commitment to human rights, his work fighting tropical diseases and for furthering democracy everywhere.

“His life offers countless lessons for leaders everywhere.”

 

“Compared with Mr. Carter, most former presidents struggled to use their stature for the common weal. Most wrote memoirs. Some disappeared into private life; some set up foundations; some went around collecting large sums for speaking. Mr. Carter took risks and played crucial roles as an honest broker in nuclear talks with North Korea and in civil conflicts on the continent of Africa and in the Middle East.

“He described his second career as 'waging peace.' That work remains far from finished, and it remains for those who admired Mr. Carter to continue.”

 

Here is how to watch and stream the funeral, from USA Today. 

Fractured fairytales

When one wave of the wand can delay or deny our dreams, I guess it’s no surprise that many of us cheer as a Prince Charming appears to take our side.

 

“Even before police arrested Luigi Mangione in connection with the killing of UnitedHealthcare CEO Brian Thompson, some on the internet were hailing him as a 21st-century Robin Hood,” Axios reported last week. And he apparently fits the part. Mangione is “by consensus, handsome, and jacked,” according to a New Yorker article. 

 

More than forty years ago, Richard Meyer, a scholar of American folklore, wrote that “the American outlaw-hero is a ‘man of the people’; he is closely identified with the common people, and, as such, is generally seen to stand in opposition to certain established oppressive economic, civil and legal systems peculiar to the American historical experience,” the New Yorker article says.

 

UnitedHealthcare is the insurance arm of the world’s biggest health-care company. You and I have talked for years about the ways health insurance denials can upend people’s finances.

 

A Reuters article explains that the 2010 Affordable Care Act (Obamacare), set new baselines for who and what insurance plans must cover. As costs have gone up, insurers increasingly have turned to the prior authorization process, vetting requests for medical services before they agree to pay.

 

Prior authorizations were used 46 million times in 2022, up from 37 million in 2019, Reuters says, citing a KFF analysis of privately managed Medicare Advantage plans for people aged 65 and older or who are disabled. CVS denied 13 percent of such requests, UnitedHealthcare denied 8.7 percent, and Blue Cross Blue Shield denied 4.2 percent.

 

Only about 10 percent of patients appeal these denials, and of those challenges, about a third fail, KFF says. Among the reasons people don’t appeal are difficulties understanding the complexity of health coverage and being too sick, says KFF.

 

United Health’s coverage limits apply to a wide range of treatments. Just four days ago, a ProPublica headline read, “UnitedHealth is strategically limiting access to critical treatment for kids with autism.” And on Nov. 19, ProPublica headlined: “How UnitedHealth’s playbook for limiting mental health coverage puts countless Americans’ treatment at risk.”

 

Yesterday’s Morning Briefing from KFF Health News was headlined “CEO was aware of UnitedHealthcare’s PR problem before shooting.” 

 

The Commonwealth Fund, an independent research organization, reported in August on ways Americans increasingly struggle to get their health insurance to work for them. 

 

Also in August, the Commonwealth Fund published “Mirror, mirror 2024: A portrait of the failing U.S. health system,” comparing performance in 10 nations. The other countries are Australia, Canada, France, Germany, the Netherlands, New Zealand, Sweden, Switzerland, and the United Kingdom.

 

“The U.S. continues to be in a class by itself in the underperformance of its health care sector,” the report says. 

 

The United States is the only developed country without universal health care coverage (government-funded insurance). 

Good news on tuberculosis, solar energy, clean water

We have a couple of issues waiting for us from our friends at Fix the News. They’re putting together their year-end wrap-up for next week, before taking a break until mid-January.

 

From the Nov. 28 edition: 

 

— Africa has made the greatest progress among all regions in tackling tuberculosis — the world’s deadliest infectious disease — with a 42 percent reduction in deaths since 2015, according to a World Health Organization report.

 

—  It took the solar PV industry 68 years to reach 1 terawatt (a trillion watts) of installed capacity — and just two more to add the second terawatt. Two terawatts of solar "is equivalent to the total installed electricity capacity of India, the USA and UK combined,” says the Global Solar Council.

 

— Between 2000 and 2020, access to safe water in China increased from 46 percent to 91 percent, according to the journal BMC Public Health.

Big Food vs. Ozempic

A friend who recently moved to France for work has been telling me what a treat it is to eat food that isn’t as ultraprocessed as it is in the United States.

 

“Ultraprocessed foods are industrial creations made with little — if any — whole foods that often contain large amounts of added sugar and salt,” says preventive cardiologist Dr. Stephen Devries, adding in an American Medical Association primer that ultraprocessed foods “are typically infused with artificial colors and additives.”

 

“Research has shown that diets high in ultraprocessed foods are linked to more than 30 health conditions,” the primer says.

 

Now The New York Times is reporting that people taking the weight-loss drugs Ozempic, Wegovy, Zepboun and others have reported losing interest in ultraprocessed foods. Some people on the drugs say that many packaged snacks they once loved now taste bad, the Times says.

 

So Big Food is scrambling to research the impact of the drugs on their brands — and figure out how to adjust. “The whole field is still a little stunned,” says Ashley Gearhardt, a food-addiction researcher and psychology professor at the University of Michigan.

There is little the industry hasn’t tried over the years to keep eaters eating, the Times says. 

 

Big Food researched the way the brain’s reward system reacts to sugar and salt, using it to keep products tickling the “bliss point,” the height of delight.

And “fortunately for the industry, people tend to want as much fat as they can get,” says the Times. Scientists can engineer fats to melt at just the right temperature in the mouth, sparking the release of dopamine while creating an impression of “vanishing caloric density.” 

"So a Cheeto, disintegrating innocently on the tongue, tells us it contains fewer calories than it does,” says the Times. 

When they discovered that noisier chips induced people to eat more of them, snack engineers increased the crunch. And they amplified the intensity of artificial sweeteners to hundreds of times beyond sugar’s natural flavor.

“In the chemosensory world,” says Dan Wesson, the director of the Florida Chemical Senses Institute, referring to the science of how chemicals provoke sensations, “almost anything is possible.”

“Given Big Food’s track record, it’s likely that the companies will succeed at finding products Ozempic users now crave,” says the Times.

How to avoid ultraprocessed foods?

 

“Looking at a nutrition label will give you an idea if a food is ultraprocessed,” says family physician Neha Sachdev, director of clinical engagement and equitable care at the AMA. “If you don’t recognize many of the ingredients listed, that can be a sign that there was a lot of processing involved.”