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Sickle cell disease is the scourge of a person’s red blood cells. The inherited blood disorder, which disproportionately affects people in sub-Saharan Africa and India, can cause unbearable pain, “crises,” and extreme exhaustion. And until recently, there was no curative treatment. Now approved gene therapies for sickle cell disease (including sickle cell anemia, the most extreme form) and its milder cousin, beta-thalassemia, show enormous promise.

The therapies work by deactivating or replacing a hemoglobin gene so that a person’s body makes a healthy form instead of the telltale sickle-shaped red blood cells that define sickle cell disease or averting the red blood cell deficiency that causes beta-thalassemia.

At some point, all humans produce two forms of hemoglobin, the red blood cell protein that binds oxygen so it can be transported throughout the body: a fetal form, which is more efficient at extracting oxygen in the womb, and an adult form. After we’re born, our body switches from producing the fetal form to making the adult form.

After years of research, scientists figured out that by turning off BCL11A—a gene known to suppress fetal hemoglobin production—they could coax the body of a person with sickle cell disease to continue making healthy hemoglobin. Companies have now developed gene therapies that target this gene. In clinical trials, people who received the treatment were functionally cured of their condition—those with sickle cell disease saw a complete resolution of their pain during the study period, and those with beta-thalassemia didn’t need blood transfusions or bone marrow transplants.

On April 18 a Breakthrough Prize in Life Sciences—one of the $3-million Breakthrough Prizes, sometimes referred to as the “Oscars of science”—was awarded to Swee Lay Thein and Stuart Orkin, who led efforts to identify the BCL11A gene and to show that shutting it off could restore healthy hemoglobin production, setting the stage for treating these devastating blood diseases.

Scientific American spoke separately with Orkin, a professor of pediatrics at Harvard Medical School and an investigator at the Dana-Farber Cancer Institute and Boston Children’s Hospital, and Thein, a senior investigator at the National Institutes of Health, about what happened in the work that led to their prize and how these treatments can be made more accessible to the people who stand to benefit the most.

How did you come to study sickle cell disease? And did you realize early on that fetal hemoglobin would be a good therapy target?

ORKIN: I started out in the 1980s working on the genetics of [beta-thalassemia]—that is, what mutations lead to the deficiency of hemoglobin in that disorder. The hope was that we would learn how a red [blood] cell is made and how genes are regulated. We didn’t really learn that, but we learned a lot about mutations and disease. Even prior to that, we knew the deficiency of beta-globin [a component of the adult hemoglobin protein] in [beta-thalassemia], and the [effects of a] mutation in sickle cell disease can be alleviated by expressing more fetal hemoglobin.

We knew that, from family studies in some very rare individuals who had a lot of fetal hemoglobin, if you raise the level of fetal hemoglobin high enough, you can basically ameliorate those disorders—plus, fetal hemoglobin is perfectly fine to substitute for adult hemoglobin [for carrying oxygen]. As early as genes were cloned back in the early 1980s, one of the goals was to see if we could reverse the switch and make fetal hemoglobin expressed at a high level in adult cells as a treatment [for beta-thalassemia]. The problem was, we didn’t understand the process at all—that’s what’s consumed the past 15 to 20 years or research—or how to reverse it.

Why do our cells switch from making fetal to adult hemoglobin in the first place?

ORKIN: We do that because, in utero, having a fetal hemoglobin is better at extracting oxygen from the mother’s circulation, and it has a higher affinity, so it takes oxygen from the circulation to the developing [fetus]. But it turns out the difference between fetal hemoglobin and adult hemoglobin in that affinity is relatively small, so having fetal hemoglobin as an adult doesn’t matter. If you ran a marathon on the top of Mount Everest, it might make a difference. You might have trouble releasing the oxygen, but under normal circumstances, it’s not a problem.

How did your work lead to the discovery of the BCL11A gene involved in sickle cell disease and beta-thalassemia?

THEIN: The discovery of BCL11A was the result of more than two decades of work driven by a deceptively simple clinical observation: Why do some people with beta-thalassemia have remarkably mild disease, while the majority require lifelong blood transfusions?

I began collecting blood samples from people with unusually mild beta-thalassemia (thalassemia intermedia) and their families. And sure enough, it turned out that most of these milder cases possessed an innate ability to produce high levels of [fetal hemoglobin]. Crucially, our family studies showed that the responsible gene or genes were inherited independently of the beta-globin gene itself and that the inheritance pattern was complex. I was convinced that that there was a substantial genetic component underlying this common [fetal hemoglobin] variation, which I confirmed with twin studies.

Then, genome-wide association studies revealed the involvement of BCL11A, a gene with no previously known role in hemoglobin biology. Our findings were independently confirmed by another group the following year, firmly establishing BCL11A as a key regulator of fetal hemoglobin and, ultimately, a therapeutic target in both sickle cell disease and beta-thalassemia.

ORKIN: Back in 2011, we did an experiment in which we took mice that had been engineered to have sickle cell anemia and disabled the BCL11A gene in those mice—but only in the developing red blood cells—through fancy genetics. The result was that we could completely correct those mice—they were completely well after we knocked out [deactivated] the BCL11A gene. That told us that one gene was sufficient to correct the disease and that it would be a therapeutic target if we could manipulate it. That was 15 years ago. It took several years to figure out where we’d want to do the editing, and just about the time we wanted to ask that question, [the gene-editing technique] CRISPR came on the scene, so, you know, all the stars aligned in just the right way.

Dr. Thein, can you describe some of your research with populations in Malawi?

THEIN:At the time, identifying the genes responsible for elevated fetal hemoglobin relied on a technique that requires large, multigenerational family cohorts with well-documented relationships. Finding such families is no small feat, so when I came across a person with exceptionally mild beta-thalassemia who happened to come from a remarkably large extended family, many of [whose members] were living in Malawi, I recognized it as a rare and significant opportunity.

I organized a field trip to Malawi and, through careful tracing and recruitment, was able to expand the study family to 210 individuals spanning seven generations—an extraordinary resource for this technique.

There was some hesitation among family members initially, which is entirely understandable when people are asked to participate in something unfamiliar. We addressed this through clear, patient explanations of the study’s purpose and what participation involved.

What had begun as a scientific endeavor became, in many ways, a communal one—a reminder that behind every dataset are real people whose generosity and trust make the research possible.

These discoveries paved the way for the first approved gene-editing treatments for sickle cell disease in 2023: Casgevy, made by Vertex Pharmaceuticals and CRISPR Therapeutics, and Lyfgenia, made by bluebird bio (now known as Genetix Biotherapeutics). How many people with sickle cell disease have received these therapies?

ORKIN:The original [Vertex] trial had [about] 75 participants [with either sickle cell disease or beta-thalassemia, and since then, they’ve treated more people. They report that more than 90 percent of the participants who were treated are basically functionally well. In other words, in the case of [beta-thalassemia], they don’t need transfusions anymore, and in terms of sickle cell disease, they don’t get sickle crises, the painful crises.

It really is transformative for these individuals, particularly for the people with sickle cell. Beforehand, it was a miserable disease. They had intermittent pain crises and other complications. And it’s hard to maintain a job if you’re an adult. And what the patients describe is, after they’re treated, they have a new lease on life.

Are the populations most at risk for these diseases likely to receive gene therapy treatment for their conditions? And how can these treatments be made more affordable and accessible?

THEIN:Honestly, in the near term, the answer is probably not.

The gene therapies currently approved by the U.S. Food and Drug Administration are ex vivo. This means harvesting a patient’s own hematopoietic [red blood] stem cells, editing them in a specialized laboratory, and then reinfusing them—but only after the patient has undergone intensive chemotherapy to destroy the existing bone marrow and create space for the edited cells to engraft [settle and begin producing new cells]. The process is physically grueling for the patient, logistically demanding and extraordinarily expensive, costing about $2 million to $3 million per patient. Even in the wealthiest health care systems, access is far from universal.

The scientific community is acutely aware of this, and research priorities are now pivoting toward next-generation in vivo gene-editing approaches where the editing machinery is delivered directly into the body to target the hematopoietic stem cells in situ.

But the challenge that weighs on me most is access to treatment, whether [it is] gene therapy, [a] bone marrow transplant or drugs. The burden of sickle cell disease is heaviest in sub-Saharan Africa and India, precisely where these therapies are currently least accessible. Even if we develop a cheaper, simpler gene therapy tomorrow, getting it to the patients who need it most will still require political will, sustained global health investment, international partnerships and a serious rethinking of how we price and distribute transformative medicines.

What are you working on next?

ORKIN: My group is focused on trying to understand in very exquisite detail the whole mechanism and the process that is involved in the switch [from fetal to adult hemoglobin]. And we’re focused on trying to see if we can develop a way to find small molecules that will do the reversion, if you will, by taking a pill. That would be something that could be distributed much more easily than the current editing therapy.

THEIN: My current research is centered on small molecules, particularly those that can prevent or abort the severe pain crises that remain one of the most debilitating and undertreated aspects of sickle cell disease. These crises represent a profound unmet clinical need, and finding effective, accessible interventions for them would make an enormous difference to patients’ daily lives.

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President Donald Trump has invited executives from some of the biggest U.S. companies — including Tesla CEO Elon Musk, Apple CEO Tim Cook, BlackRock’s CEO Larry Fink, and Boeing CEO Kelly Ortberg — to join his trip to China this week, according to a White House official.

Also expected to join Trump’s delegation for meetings with Chinese President Xi Jinping are Blackstone’s Stephen Schwarzman, Cargill’s Brian Sikes, Citigroup’s Jane Fraser, Coherent’s Jim Anderson, GE Aerospace’s H. Lawrence Culp Jr., Goldman Sachs’s David Solomon, Illumina’s Jacob Thaysen, Mastercard’s Michael Miebach, Meta Platforms executive Dina Powell McCormick, Micron Technology’s Sanjay Mehrotra, Qualcomm’s Cristiano Amon and Visa’s Ryan McInerney, the official said, speaking on condition of anonymity because the list has not been announced.

A spokesperson for Cisco said CEO Chuck Robbins had been invited by the White House to join the trip but is unable to attend due to the company’s earnings schedule.

The executives will join Trump on the trip during which he has said he hopes to secure a series of business deals and purchase agreements with Beijing.

The summit agenda is expected to cover trade, artificial intelligence, export controls, Taiwan, and the Iran war, with both sides entering the talks after weeks of escalating tensions. 

Notably absent from the attendees is Nvidia CEO Jensen Huang, who said last week in an interview with CNBC’s Jim Cramer that “We should let the president announce whatever he decides to announce … If invited, it would be a privilege, ​it would be a great honor to represent the United States.”

General Motors, Disney, and Alphabet are also companies with interests in China that the White House did not list as having executives expected to attend.

On Friday, Citigroup’s Fraser told CNBC’s Leslie Picker that “I think it’s very important to see engagement” between the two economic superpowers.” Adding, “we all need that engagement to be occurring.”

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What We’re Covering Today

• FEMA Administrator: President Trump nominated Cameron Hamilton, a former acting administrator of the Federal Emergency Management Agency, to be FEMA’s permanent leader on Monday. He was pushed out of the acting role a year ago after he did not endorse eliminating the agency, which Mr. Trump had suggested. Mr. Hamilton, a former Navy SEAL, is likely to face opposition from Democrats because he lacks experience in disaster response.

• Reflecting Pool: Federal records show that the no-bid contract to repair the Lincoln Memorial Reflecting Pool and paint it blue now costs $13.1 million — more than seven times the amount President Trump initially said it would.

• China Trip: Mr. Trump will be joined by 16 top executives in China this week, including Elon Musk and Tim Cook.

 

Trump nominates an ousted FEMA leader to run the agency again.

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President Trump on Monday nominated Cameron Hamilton, a former member of the Navy SEALs, as administrator of the Federal Emergency Management Agency, seeking to install the organization’s first permanent leader of the president’s second term.

If confirmed by the Senate, Mr. Hamilton would rejoin the agency a year after serving a brief stint as its acting administrator. He was ousted from that role days after he testified to Congress that FEMA should not be eliminated, an idea that Mr. Trump and Kristi Noem, then the homeland security secretary, had floated early last year. 

The cost of repairing the National Mall reflecting pool is far more than Trump initially said.

President Trump said that his handpicked contractor would charge only $1.8 million to repair the Lincoln Memorial Reflecting Pool and paint it blue.

The actual cost is now more than seven times that, after the Interior Department nearly doubled the size of the contract late last week, federal records show.

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The U.S. Senate has confirmed Steve Pearce to steward about 245 million acres of federal land and 700 million acres of underground minerals as director of the Bureau of Land Management. Pearce, a Republican former U.S. representative from New Mexico, faced opposition from conservation and hunting groups for his past support of privatizing public lands. During his confirmation hearing, though, Peace pledged he would not pursue sales of “large swaths” of federal holdings. The 46-45 vote along party lines confirmed a large bloc of nominees to energy and environment positions, including Pearce.A third federal appeals court has rejected the Trump administration’s policy of detaining U.S. residents who entered the country illegally years ago and holding them without bond. The majority opinion in the split ruling from the U.S. Court of Appeals for the Sixth Circuit is the first by a federal appeals court to affirmatively find that not only does the policy rest upon a misinterpretation of immigration law, it also violates the Fifth Amendment’s guarantee to due process. Both questions are likely to reach the Supreme Court.

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Senate Republicans on Monday defended their plan to include $1 billion for security funding for President Trump’s ballroom project as they prepared to take up a politically charged budget bill that faces stiff opposition from Democrats.

Returning to the Capitol for the first time since the components of the spending plan were made public, top Republicans said the security money was necessary given the threats to the president, and claimed that none of it would be used for the ballroom itself. The president has said private donations will pay for the ballroom, which he has estimated to cost $400 million, though some Republicans want tax dollars to go to it as well.

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James Comey, the former F.B.I. director, took aim at President Trump during his first interview since being indicted over his social media post of seashells on a beach, told MSNOW it was a “little bit humorous” to have “this obsession by this 80-year-old man with me.” He also took a swipe a Joseph Joseph diGenova, who was recently tapped to oversee investigations of Trump enemies, quipping that the 81-year-old ex-prosecutor had not served in government “since Duran Duran was on the charts.” Comey, targeted for his investigation into the 2016 Trump campaign’s connections to Russia, lamented that his successor, Christopher Wray, had not spoken up about Trump and his appointees at the F.B.I. Comey said he hoped Wray and others have not been “chilled” by Trump — whom he called “an empty narcissist.”

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Cameron Hamilton attending a hearing at the Capitol last year as the acting administrator of the Federal Emergency Management Agency. Credit…Oliver Contreras/Agence France-Presse — Getty Images

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Microplastic particles flowing through Earth’s atmosphere may be quietly driving up global temperatures, a new study suggests.

Microplastics and nanoplastics—tiny bits of broken-down plastic pollution—litter the planet’s rivers, oceans, land, and air. But until now, researchers weren’t sure what effect all those plastic particles were having on an already warming climate.

A new study led by researchers at Fudan University in China suggests that the particles may significantly affect warming—for comparison, microplastics’ warming effect equates to about 16 percent of that of black carbon, or soot.

“This article shows a very worrying truth about the dangers of micro- and nanoplastics,” says Steve Allen, a microplastics researcher at the environmental advocacy organization Healthy Earth, who was not involved with the study.

If you’ve ever walked barefoot on asphalt, you know black material absorbs heat. White paint on asphalt, however, reflects it. The same thing happens with airborne microplastics—darker colors warm the atmosphere, while lighter colors help cool it. By analyzing the optical properties of various microplastics in the lab and simulating their effect on a global scale, the new study’s authors estimated that microplastics’ warming abilities outweigh their potential cooling effects—something current climate models don’t account for.

The results were published on Monday in Nature Climate Change.

The findings reveal “a long-overlooked link” between plastics and climate change, said study co-author Hongbo Fu, a researcher at Fudan University in China, at a press conference. Plastics are not just an environmental pollutant. “They can also act as a heating agent in the atmosphere,” he said.

“We still have a lot to learn about exactly how many of these [microplastics] are in the atmosphere and how they’re distributed, both horizontally and vertically,” said Drew Shindell, the study’s senior author and a professor of Earth science at Duke University, at the same press conference. “This is not the final word.”

It’s unclear how many microplastics are actually in the atmosphere. But the study team argues global climate assessments, such as those published by the Intergovernmental Panel on Climate Change (IPCC), need to factor in these particles. “Our work suggest that climate models need to be updated,” Fu said. “IPCC should take notice.”

More broadly, Allen says the results underscore the need to reduce our reliance on plastics—which are often made from the by-products of fossil fuel production.

“What needs to be looked at is the carbon emissions throughout the life cycle of plastic production, adding to the total climate change effect,” he says. The “takeaway message” is “that we can reduce climate change by removing plastic from our lives.”

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Babies are on the way!

And some are already here. Every year, one of our favorite roundups to do is the list of well-known women who are expecting. The lists always start small and blossom to more than 30, 40 ladies by the end of the year.

To kickstart the list, we’ve gathered up big screen stars, football wives, the partners of hip-hop stars, and more.

The latest mama-to-be is attorney and TV personality, Judge Faith Jenkins. She shared the news, alongside her husband, singer Kenny Lattimore, that the couple is expecting their second child in May. In their announcement, they previewed a rendition of “Somewhere Over the Rainbow,” sung by Lattimore, which Jenkins noted is “one of the baby’s favorite songs.”

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NEW ORLEANS, LOUISIANA – JULY 06: Judge Faith Jenkins (L) and Kenny Lattimore attend The National Urban League’s 2024 Women in Harmony Award at The Ritz-Carlton New Orleans on July 06, 2024, in New Orleans, Louisiana. (Photo by Aaron J. Thornton/Getty Images)

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Democrats are struggling to respond to a major redistricting setback in Virginia, with some party leaders discussing an audacious and possibly far-fetched idea for trying to restore a congressional map voided by the court but showing little indication they have a clear plan.

During a private discussion on Saturday that included Democratic House members from Virginia and Representative Hakeem Jeffries of New York, the minority leader, the lawmakers vented anger at their defeat at the Virginia Supreme Court, spoke about a collective determination to flip two or three Republican-held seats under the existing map and discussed a bank-shot proposal to redraw the congressional lines anyway, according to three people who participated in the call and two others who were briefed on it.

They did not land on a specific course forward, and Mr. Jeffries and the other members of Congress agreed to consult with their lawyers about the most prudent way to proceed, said the people, who spoke on the condition of anonymity to describe a private talk.

The conversation reflected the desperation and fury that have gripped the party after the state Supreme Court struck down a favorable map that had been ratified by voters. The most dramatic idea they discussed — which would involve an unusual gambit to replace the entire state Supreme Court, with a goal of reinstating their gerrymandered map — drew mixed reactions on the call, said the people, and it was not clear that it would even be viable, or palatable to Gov. Abigail Spanberger and Democrats in the Virginia General Assembly.

After Democrats had fought Republicans to a rough draw last month in a nationwide gerrymandering war, a pair of recent court rulings quickly gave the G.O.P. the clear upper hand in the race to redraw maps ahead of the midterm elections. Facing stiff headwinds, including President Trump’s low approval ratings and high gas prices, Republicans are looking for every advantage they can find to defy the odds and hold on to their narrow majority.

Any plans to enact a new congressional map for this year’s midterm elections would require action in the next few days. In a court filing last month, Steven Koski, the commissioner of the Virginia Department of Elections, said any changes to the maps after Tuesday, May 12, “will significantly increase the risk” of his agency being unable to properly prepare for the state’s scheduled Aug. 4 primary election.

A spokesman for Mr. Jeffries declined to comment.

Scott Surovell, the majority leader of the Virginia Senate, declined to comment on Saturday evening. Don Scott, the speaker of the state House of Delegates, said in an interview that he had not spoken to Mr. Jeffries or members of the congressional delegation about the multistep proposal that came up in the discussion.

One key to the plan would be having Democrats in Richmond lower the mandatory retirement age for state Supreme Court justices, an idea that began circulating among state lawmakers and members of Congress after a column proposing a version of the idea was published on Friday night in The Downballot, a progressive newsletter.

Ms. Spanberger would have to sign off on any legislation that lowered the judicial retirement age. She has not been briefed on the proposal, the people involved in the discussion or briefed on it said. Her spokeswoman, Libby Wiet, declined to comment.

The first step in the process, as discussed on the delegation’s call, would be to invoke a January ruling by a circuit court judge in Tazewell County, Va., that said the 2026 constitutional amendment effort to redraw the maps was invalid because county officials did not post notice of it at courthouses and other public locations three months before a general election.

Democrats would aim to use that ruling to seek to invalidate the earlier constitutional amendment that created the state’s independent redistricting commission by arguing that courthouses across the state did not post notice of it at the time. That would give the legislature the authority to enact a map of its choosing.

Ensuring the plan proceeds would involve the General Assembly, which is controlled by Democrats, lowering the mandatory retirement age for Virginia’s Supreme Court from 75 to 54, the age of the youngest current justice, or less. Virginia judges are appointed by the General Assembly, where Democrats hold majorities in both chambers and could then fill vacancies on the court with sympathetic Democratic lawyers.

Mandatory retirement ages are in place for judges in 32 states and Washington, D.C., according to a 2015 law review article from the Duke University Law School. The article said the most common retirement age set by states is 70.

In states such as Arizona, Georgia, and Utah, Republican lawmakers have expanded state Supreme Courts in order to make them more conservative. But the Virginia proposal, which would get rid of all the sitting judges, would go considerably further.

Former Representative James P. Moran, Democrat of Virginia, said a move to stack the Virginia Supreme Court would be “just a bridge too far” and could backfire on his party.

He said he understood that many Democrats felt that their party “needs to fight back and not just be victims of unparalleled aggression.” But, he added, “We do have to keep our credibility. We have to do things that pass the legitimacy test.”

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Representative Hakeem Jeffries of New York, the minority leader, speaking at the Capitol in Washington last month. Credit…Kenny Holston/The New York Times

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