The genetic treatment targeted a particular kind of congenital deafness and will soon be tried in children who are younger.Aissam Dam, an 11-year-old boy, grew up in a world of profound silence. He was born deaf and had never heard anything. While living in a poor community in Morocco, he expressed himself with a sign language he invented and had no schooling.Last year, after moving to Spain, his family took him to a hearing specialist, who made a surprising suggestion: Aissam might be eligible for a clinical trial using gene therapy.On Oct. 4, Aissam was treated at the Children’s Hospital of Philadelphia, becoming the first person to get gene therapy in the United States for congenital deafness. The goal was to provide him with hearing, but the researchers had no idea if the treatment would work or, if it did, how much he would hear.The treatment was a success, introducing a child who had known nothing of sound to a new world.“There’s no sound I don’t like,” Aissam said, with the help of interpreters during an interview last week. “They’re all good.”While hundreds of millions of people in the world live with hearing loss that is defined as disabling, Aissam is among those whose deafness is congenital. His is an extremely rare form, caused by a mutation in a single gene, otoferlin. Otoferlin deafness affects about 200,000 people worldwide.The goal of the gene therapy is to replace the mutated otoferlin gene in patients’ ears with a functional gene.Although it will take years for doctors to sign up many more patients — and younger ones — to further test the therapy, researchers said that success for patients like Aissam could lead to gene therapies that target other forms of congenital deafness.It is a “groundbreaking” study, said Dr. Dylan K. Chan, a pediatric otolaryngologist at the University of California, San Francisco, and director of its Children’s Communication Center; he was not involved in the trial.The one in which Aissam participated is supported by Eli Lilly and a small biotechnology firm it owns, Akouos. Investigators hope to eventually expand the study to six centers across the United States.Special earphones being used for Aissam’s hearing test. His form of deafness is rare, caused by a mutation in a single gene, otoferlin. Hannah Beier for The New York TimesAissam’s trial is one of five that are either underway (the others are in China and Europe) or about to start.Investigators from all five of the studies will be presenting their data on Feb. 3 at a meeting of the Association for Research in Otolaryngology.The studies, researchers said, mark a new frontier for gene therapy which, until now, had steered clear of hearing loss.“There has never been a biological or medical or surgical way to correct the underlying biological changes that cause the inner ear to not function,” Dr. Chan said.Although otoferlin mutations are not the most common cause of congenital deafness, there is a reason so many researchers started with it. That form of congenital deafness, said Dr. John A. Germiller, an otolaryngologist who is leading the CHOP study, is “low hanging fruit.”The mutated otoferlin gene destroys a protein in the inner ear’s hair cells necessary to transmit sound to the brain. With many of the other mutations that cause deafness, hair cells die during infancy or even at the fetal stage. But with otoferlin deafness, hair cells can survive for years, allowing time for the defective gene to be replaced with gene therapy.Aissam’s trial at the Children’s Hospital of Philadelphia is among five that are either underway (the others are in China and Europe) or about to start.Hannah Beier for The New York TimesThere’s an advantage in using gene therapy to allow children to hear. Most of the mutations that affect hearing — there are approximately 150 — do not affect any other part of the body. Some genes are actually unique to the ear.The inner ear is a small closed compartment, so gene therapy delivered there would not affect cells in other parts of the body, said Manny Simons, chief executive and co-founder of Akouos and senior vice president of gene therapy at Lilly.But getting the genes to the cochlea, a spiral-shaped cavity close to the center of the skull, is challenging. The cochlea is filled with fluid, is lined with 3,500 hair cells and is encased in a dense dome of bone with a tiny, round membrane. Sound sets off a wave of fluid in the cochlea and stimulates the hair cells to transmit signals to the brain. Each hair responds to a different frequency, enabling a person to hear the richness of sound.The gene therapy consists of a harmless virus carrying new otoferlin genes in two drops of liquid that are delicately injected down the length of the cochlea, delivering the genes to each hair cell.Yet despite the promise of otoferlin gene therapy, finding the right patients for the trial was difficult.One issue is the very idea of treating deafness.“There is an internal Deaf community that doesn’t see itself as needing to be cured,” said Dr. Robert C. Nutt, a developmental and behavioral pediatrician in Wilmington, N.C., who is deaf.Some Deaf parents, he added, celebrate when their newborn baby’s hearing test indicates that the baby is deaf too and so can be part of their community.Making the issue of gene therapy even more complicated is the standard intervention for otoferlin hearing loss: a cochlear implant. The device, which uses electrodes to stimulate auditory nerves in the inner ear, allows patients to hear sounds, especially those needed to understand speech. But the implant does not provide the full richness of sound — and is said to assist in hearing but without restoring it completely.Dr. John Germiller, an otolaryngologist who is leading the CHOP study.Hannah Beier for The New York TimesMost babies born with otoferlin deafness get cochlear implants in infancy and are therefore ineligible for the trial. The implants somewhat alter the cochlea, which could hamper the interpretation of gene therapy results.The Food and Drug Administration, which allowed the CHOP study to go forward, asked that, for safety reasons, the researchers start with older children, not infants, and treat only one ear.The challenge for the U.S. study was to find older children whose parents would agree to the study, who had otoferlin deafness and who did not have cochlear implants.Aissam never had cochlear implants. He never had schooling in Morocco to help him develop communication skills. But three years ago, when he was 8, his father, Youssef Dam, a construction worker, got a job in Barcelona, Spain. For the first time, Aissam went to school, enrolling in a school for the deaf, where he learned Spanish Sign Language. Soon after, his family learned of the gene therapy trial.When Aissam was deemed eligible to be patient No. 1, Lilly and Akouos paid for him and his father to live in Philadelphia for four months, while Aissam received gene therapy and follow-up hearing tests.No one knew whether the nerve cells that communicate with the hair cells of the cochlea would still be intact and functional in someone who had been deaf for 11 years, Dr. Simons of Lilly said.It was not even clear what dose of the new genes to give. All that the researchers had to go on were studies with mice. “We were flying blind,” Dr. Germiller said.Aissam’s results, his doctors said, were remarkable. In an interview at CHOP, his father said through an interpreter — he speaks a North African language from the Amazigh family, commonly known as Berber — that Aissam was hearing traffic noises just days after the treatment. When Aissam had a hearing test two months later, his hearing in the treated ear was close to normal.But no matter how well the gene therapy works, the researchers recognize that Aissam may never be able to understand or speak a language, Dr. Germiller said. The brain has a narrow window for learning to speak beginning around ages 2 to 3, he explained. After age 5, the window for learning spoken language is permanently shut.Hearing can still help patients even if they never learn to speak, he noted. They can hear traffic or know when someone is trying to communicate. The ability to hear also can help with lip reading.Aissam signing to an interpreter during an interview at the children’s hospital.Hannah Beier for The New York TimesNow that gene therapy has proved safe for Aissam and for another child in Taiwan treated two months after him, researchers at the hospital in Philadelphia are able to move on to younger children. They have two lined up, a 3-year-old boy from Miami and a 3-year-old girl from San Francisco, both of whom got cochlear implants in only one ear, so that the other could be treated with gene therapy.If the Lilly trial of otoferlin gene therapy is proved to be effective and safe, “there will be a lot of interest in other genes” that cause deafness, said Dr. Margaret A. Kenna, an otolaryngologist at Boston Children’s Hospital and professor of otolaryngology at Harvard Medical School.Dr. Kenna, an investigator in the Lilly trial, added, “It’s been a long time coming.”“For decades people have been saying, ‘When is this going to work?’” Dr. Kenna said. “I didn’t think gene therapy would begin in my practice lifetime. But here it is.”Of the other studies, two are in China where investigators are treating younger children and in both ears. Results from one, supported by the National Natural Science Foundation of China and Shanghai Refreshgene Therapeutics, will be reported Wednesday in the journal The Lancet. The other is supported by Otovia Therapeutics and various programs in China.A third study is sponsored by Regeneron and Decibel Therapeutics. Researchers in Europe so far have treated one child, who is younger than 2, and in one ear. Another study by Sensorion is expected to start this month.On a recent frigid morning, Aissam sat in a conference room at CHOP and, with the help of three translators, patiently answered questions about his remarkable experience. He’s a solemn child with a round face and big brown eyes. There was an interpreter for his father, and the sign language team had a Certified Deaf Interpreter — a person who is deaf translated his signs into American Sign Language — and an interpreter who knew American Sign Language and spoke his words.Their system worked to a certain extent but robbed the conversation of spontaneity and forced Aissam to answer in short sentences or phrases, minimizing the expression of his personality.But Aissam managed to convey the wonder of hearing.Noises and voices frightened him initially, he said. But then, as the world of sound opened up, he began to enjoy every sound he heard — elevators, voices, the sound of scissors snipping his hair at a barbershop.And there was music, which he heard for the first time one day while getting his hair cut.Asked if there was a sound he particularly liked, Aissam did not hesitate.“People,” he signed.

When medicine does not ease an enlarged prostate, known also as BPH, a common surgery with few risks is often used.King Charles III will have a procedure to address an enlarged prostate at a hospital next week. The 75-year-old British monarch’s diagnosis is common among men his age, and experts say that typical treatments are not dangerous.An enlarged prostate, known also as benign prostatic hyperplasia, or BPH, is a noncancerous condition that occurs frequently among older men. By age 60, more than half of men have at least mild BPH symptoms, which include difficulty urinating and a sense of urgency to urinate. But often the symptoms are not severe enough to require treatment.The condition is analogous to menopause in women, said Dr. Peter Albertsen, a urologist and prostate specialist at the University of Connecticut. Menopause usually begins around age 50 when levels of testosterone and estrogen start changing. The same thing happens in men, Dr. Albertsen said, and at the same age.“We think it’s the changing ratio of testosterone to estrogen,” he said. “The way the male responds is that the prostate enlarges. It’s a normal process of aging.”The prostate is shaped like a doughnut surrounding the urethra, the tube that carries urine from the bladder to the penis. When the prostate grows, the tube gets squeezed, said Dr. Judd W. Moul, a urologist and prostate specialist at Duke University.Most men notice symptoms, he added. They urinate more often, they get up at night to urinate. Their urine stream is more feeble.If symptoms get more severe, men usually are treated with medications to relax the prostate. Dr. Albertsen said that doctors typically start by prescribing an alpha blocker, like terazosin (Hytrin), doxazosin (Cardura), tamsulosin (Flomax), alfuzosin (Uroxatral) or silodosin (Rapaflo).Another choice is finasteride (Proscar or Propecia), which blocks the conversion of testosterone to dihydrotestosterone, the hormone that causes the prostate to enlarge.If the prostate continues to grow despite medical treatment — which can happen when men reach Charles’s age — some may need surgery.Buckingham Palace did not describe on Wednesday the procedure Charles would undergo. But experts say that the most common and appropriate treatment is a transurethral resection of the prostate, or TURP. A surgeon scrapes out the inside of the prostate gland, giving the urethra more space. The operation has been used for 100 years, Dr. Moul said.Men who have a TURP usually go home that day or the next, and have a catheter to drain urine for the next day or two.More recently, new surgical treatments have been introduced, including an electrical cutting loop to destroy prostate tissue, steam to vaporize prostate tissue and a system that uses implants to hold the prostate away from the urethra.Although the techniques vary, all the operations have the same goal — making the prostate smaller.“The best operation,” Dr. Moul said, “is the one the most experienced surgeon does expertly.”None of the operations is debilitating, Dr. Albertsen added.Surgery for benign prostatic hypertrophy “is no big deal,” he said.

The newsCancer deaths in the United States are falling, with four million deaths prevented since 1991, according to the American Cancer Society’s annual report.At the same time, the society reported that the number of new cancer cases had ticked up to more than two million in 2023, from 1.9 million in 2022. Cancer remains the second leading cause of death in the United States, after heart disease. Doctors believe that it is urgent to understand changes in the death rate, as well as changes in cancer diagnoses.Breast cancer mortality is one area where treatment has had a significant impact. Miguel Roberts/The Brownsville Herald, via Associated PressBackground: Treatment improvements help reduce cancer deaths.The cancer society highlighted three chief factors in reduced cancer deaths: declines in smoking, early detection and greatly improved treatments.Breast cancer mortality is one area where treatment had a significant impact.In the 1980s and 1990s, metastatic breast cancer “was regarded as a death sentence,” said Donald Berry, a statistician at the University of Texas MD Anderson Cancer Center and an author of a new paper on breast cancer with Sylvia K. Plevritis of Stanford University and other researchers (several authors of the paper reported receiving payments from companies involved in cancer therapies).The paper, published Tuesday in JAMA, found that the death rate from breast cancer had fallen to 27 per 100,000 women in 2019 from 48 per 100,000 in 1975. That includes metastatic cancer, which counted for nearly 30 percent of the reduction in the breast cancer death rate.Breast cancer treatment has improved so much that it has become a bigger factor than screening in saving lives, said Ruth Etzioni, a biostatistician at the Fred Hutchinson Cancer Center.Death rates have even declined among women in their 40s, who generally did not have regular mammograms, said Dr. Mette Kalager, a professor of medicine at the University of Oslo and Oslo University Hospital, “indicating a substantial effect of treatment,” she said.“The biggest untold story in breast cancer is how much treatment has improved,” said Dr. H. Gilbert Welch, a cancer epidemiologist at Brigham and Women’s Hospital. “This is unambiguous good news.”What We Don’t Know: The cause of new cancer cases.We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? 

The effects of drugs that treat Alzheimer’s, cancer and other illnesses are often limited by the blood-brain barrier. A small study suggests a way forward.There is a problem with the recently approved Alzheimer’s drug, Aduhelm. It can remove some of the amyloid that forms brain plaques that are hallmarks of the disease. But most of the drug is wasted because it hits an obstacle, the blood-brain barrier, that protects the brain from toxins and infections but also prevents many drugs from entering.Researchers wondered if they could improve that grim result by trying something different: they would open the blood-brain barrier for a short time while they delivered the drug. Their experimental method was to use highly focused pulses of ultrasound along with tiny gas bubbles to pry the barrier open without destroying it.The investigators, at the Rockefeller Neuroscience Institute at West Virginia University, reported their results last week in The New England Journal of Medicine. When the barrier was opened, 32 percent more plaque was dissolved, said Dr. Ali Rezai, a neurosurgeon at the institute, who led the study. The group did not measure the amount of antibody getting in — that would require radioactively labeling the drug — but in animal studies opening the barrier allowed 5 to 8 times more antibody to enter the brain, Dr. Rezai said.The early-stage experiment, which was only tried in three patients with mild Alzheimer’s, was funded by the university and the Harry T. Mangurian, Jr. Foundation.We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? 

The research, supported by the National Institutes of Health, may reassure some patients after a European drug safety agency raised concerns last year.People taking the wildly popular drugs Ozempic, to treat diabetes, and Wegovy, to combat obesity, are slightly less likely to have suicidal thoughts who are not taking them, researchers reported on Friday.Millions of people take Ozempic and Wegovy, which are considered to be among the biggest blockbusters in medical history. But last year a European drug safety agency said it was investigating whether the drugs cause suicidal thoughts. The new study, published in the journal Nature Medicine, was funded by the National Institutes of Health and used a huge population. The findings provide data that may potentially reassure people who take the drugs.Novo Nordisk, maker of the drugs, had no role in the study, and the study’s investigators had no conflicts of interest.The investigators used anonymized electronic health records from a database of 100.8 million people. That allowed them to look at two groups: 240,618 who were prescribed Wegovy or other weight loss drugs, and 1,589,855 who were prescribed Ozempic or other medicines to lower their blood sugar. Suicidal thoughts were included in patients’ records as part of routine monitoring of their health.The investigators compared the incidence of suicidal thoughts in people who were taking the drugs with the incidence among similar people who were not taking them but were taking other weight loss and anti-diabetes medications. They also asked if there was an increase in the recurrence of suicidal thoughts among those taking the drugs who had previously reported thoughts of suicide.The database’s size allowed the researchers to look at subgroups such as sex, race and age groups.“No matter how hard we tried we did not see any increased risk,” said Rong Xu, director of the Center for Artificial Intelligence in Drug Discovery at Case Western Reserve University in Cleveland.We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? 

Pediatricians are hesitating to prescribe medicines like Wegovy, citing their newness and uncertainties around them.Dr. Edward Lewis, a pediatrician in Rochester, N.Y., has seen hundreds of children with obesity over the years in his medical practice. He finally may have a treatment for their medical condition — the powerful weight loss drug Wegovy.But that does not mean Dr. Lewis is prescribing it. Nor are most other pediatricians.“I am reluctant to prescribe medications we don’t use on a day-to-day basis,” Dr. Lewis said. And, he added, he is disinclined to use “a medicine that is a relative newcomer to the scene in kids.”Regulators and medical groups have all said that these drugs are appropriate for children as young as 12. But like Dr. Lewis, many pediatricians hesitate to prescribe Wegovy to young people, fearful that too little is known about long term effects, and mindful of past cases when problems emerged years after a drug was approved.Twenty-two percent of adolescents age 12 to 19 have obesity. Research shows that most are unlikely to ever overcome the condition — advice to diet and exercise usually has not helped. The reason, obesity researchers say, is that obesity is not caused by a lack of will power. Instead, it is a chronic disease characterized by an overwhelming desire to eat.We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? 

People with the genetic disease have new opportunities to eliminate their symptoms, but the treatments come with obstacles that limit their reach.On Friday, the Food and Drug Administration approved the first gene editing therapy ever to be used in humans, for sickle cell disease, a debilitating blood disorder caused by a single mutated gene.The agency also approved a second treatment using conventional gene therapy for sickle cell that does not use gene editing.For the 100,000 Americans with the disease, most of them Black, the approvals offer hope for finally living without an affliction that causes excruciating pain, organ damage and strokes.While patients, their families and their doctors welcome the F.D.A.’s approvals, getting either therapy will be difficult, and expensive.“It is practically a miracle that this is even possible,” said Dr. Stephan Grupp, chief of the cellular therapy and transplant section at Children’s Hospital of Philadelphia. Dr. Grupp, who consults for Vertex, said his medical center was hoping to begin treating sickle cell patients next year.But, he added, “I am very realistic about how hard this is.”The obstacles to treatment are myriad: an extremely limited number of medical centers authorized to provide it; the requirement that each patient’s cells be edited or have a gene added individually; procedures that are so onerous that not everyone can tolerate them; and a multimillion-dollar price tag and potential insurance obstacles.As a result, sickle cell experts said, only a small fraction of patients in the United States are expected to receive the new treatment (to say nothing of the millions of sickle cell patients overseas, particularly in Africa, for whom it may be completely out of reach for now). The F.DA. estimates that about 20,000 patients — who are 12 and older and have had episodes of debilitating pain — will be eligible for the therapies.The gene editing treatment, called Exa-cel and using the brand name Casgevy, was jointly developed by Vertex Pharmaceuticals of Boston and CRISPR Therapeutics of Switzerland. It uses CRISPR, the Nobel Prize-winning gene editing tool, to snip patients’ DNA. For a small number of subjects in clinical trials, it corrected the effects of the mutation, which results in red blood cells that are shaped like sickles or crescents that become caught in blood vessels, blocking them.Casgevy is the first treatment to be approved that uses CRISPR. Patients will also need expensive, intensive medical care and a long hospitalization.The other treatment, called Lyfgenia and made by Bluebird Bio of Somerville, Mass., uses a common gene therapy method to add a good hemoglobin gene to patients’ DNA.Vertex says its price to edit a patient’s genes will be $2.2 million; for, Bluebird it will be $3.1 million.But living with the disease is also extremely costly: On average, $1.7 million for those with commercial insurance over a patient’s lifetime. Patients themselves may pay about $44,000 out of pocket on average over the course of their lives.For patients and the doctors who treat them, it is tantalizing to think of being free from the complications of sickle cell. So despite the many unknowns, medical centers say they are compiling lists of interested patients who are ready to pursue treatment when it becomes available.“We are talking for the first time about survivorship,” said Dr. Sharl Azar, medical director of the comprehensive sickle cell disease treatment center at Massachusetts General Hospital. Patients, said Dr. Azar, who previously consulted for Vertex, are starting to hope they can live into their 70s and 80s rather than dying young.Opportunities and ObstaclesIn clinical trials, Exa-cel corrected the effects of a mutation in red blood cells that forms shapes like sickles or crescents that become caught in blood vessels, blocking them.BSIP SA/Alamy Treatment will start with hospital visits to collect patients’ bone marrow stem cells — the precursors of red blood cells that are treated to enable the production of healthy blood cells. Stem cells must be released from the marrow into the blood so they can be collected. To release them, doctors inject patients with a drug, plerixafor.It can take months to get enough stem cells to send to a central facility for treatment. And Vertex has only one gene editing facility in the United States, in Tennessee, and one in Europe, in Scotland. Bluebird’s facility is in New Jersey.After editing a patient’s cells with CRISPR, technicians do a sequence of quality checks. About 16 weeks after the process begins, the cells will be shipped back to the medical center to be infused into the patient, said Dr. Julie Kanter, director of the adult sickle cell center at the University of Alabama at Birmingham.At that point, doctors must clear the patient’s marrow with intensive chemotherapy to make way for the new cells. Patients remain in the hospital for a month or more while their edited stem cells repopulate their marrows, during which time they have no functioning immune system.That is if they can find a medical center that offers the new therapy. Most hospitals will not be able to offer Casgevy even if they want to. So far, Vertex has authorized only nine centers to provide its treatment. The company says it will eventually authorize about 50.Bluebird has 27 authorized centers and also plans to add more.The gene editing treatment is so challenging and requires so many resources that leading medical centers say that even if they are authorized to provide it they would probably only be able to treat a small number of patients a year.“We can’t do more than 10 a year,” said Dr. Kanter, who has in the past consulted for Vertex and Bluebird Bio.And, Dr. Kanter said, “we’re really good at it,” adding that her medical center had extensive experience treating sickle cell patients and participating in the Bluebird clinical trials.Others said the same. “Five to 10 a year,” said Dr. Jean-Antoine Ribeil, clinical director of the Center of Excellence in Sickle Cell Disease at Boston Medical Center, which says it is the largest sickle cell center in New England and is one approved by Vertex to offer its therapy.Vertex has not revealed how many patients’ cells it will be able to edit each year, saying only that it is confident it can meet the demand at the time the treatment is introduced.Nor has Bluebird. But, Dr. Grupp said, Bluebird’s gene therapy for thalassemia — a genetic disorder in which the body does not make enough hemoglobin — gives a hint. Bluebird, he said, has only been able to treat the cells of 50 patients a year since the drug was approved in August 2022. And that is “for the entire country,” Dr. Grupp said.Insurance payments pose another obstacle. Before treatment starts, a patient’s insurer has to agree to pay. That can take months, said Dr. David Jacobsohn, chief of the division of blood and marrow transplantation at Children’s National Hospital in Washington. His medical center is among those authorized to provide the Vertex and the Bluebird treatments.Most sickle cell patients are insured through Medicaid, noted Dr. John DiPersio, director of the Center for Gene and Cellular Immunotherapy at the Washington University School of Medicine in St. Louis. Dr. DiPersio consults for Vertex and Bluebird.“If every sickle cell patient in Missouri gets treated, the state couldn’t afford it,” he said.Another concern involves unknowns about the new therapy. While a panel of F.D.A. experts concluded that the benefits outweighed the risks, doctors remain mindful of unexpected outcomes.“We don’t know yet what the long-term effects will be,” Dr. DiPersio said. “We haven’t followed patients long enough — just a couple of years.” And stem cells, he added, “will live forever,” so if CRISPR or the Bluebird gene therapy does genetic damage, it will remain.Exa-cel was jointly developed by Vertex Pharmaceuticals of Boston and CRISPR Therapeutics of Switzerland.Joseph Prezioso/Agence France-Presse — Getty ImagesHow Patients and Doctors FeelHaja Sandi, a 19-year-old student at Rowan University in New Jersey, hopes to be at the top of the list at the Children’s Hospital of Philadelphia.She has frequent hospitalizations for pain so intense she has to take morphine. Her symptoms have forced her into remote schooling. “There is no way I could do it in person,” she said.Hearing about the Vertex therapy, she contacted the hospital in Philadelphia asking if she could get it.“God willing, I will go forward with it,” she said.The Children’s Hospital of Philadelphia, among others, is hoping to get on Vertex’s list of approved centers and is planning to take eligible patients on a first-come-first-served basis.Still others, like Children’s National Hospital in Washington, will give priority to the sickest patients.Dr. Azar intends to take a different approach if Massachusetts General is approved. He said he wanted to proceed with extreme caution, starting with just one patient and going through the entire process before accepting more.He worries that a misstep could sully the treatment for those who could be helped.Going forward, the therapies will be provided without the extensive support that the companies gave to clinical trial participants. And it will be a test case for using CRISPR gene editing to treat other diseases. CRISPR Therapeutics is now studying gene editing to treat cancer, diabetes, and A.L.S., among others.“It is a blessing and curse that we are going first,” Dr. Azar said. “Sickle cell disease has never been first for anything.”The people seeking the therapy — mostly Black patients — often mistrust the health care system, he added.“We want to do this right,” Dr. Azar said. “We don’t want patients to feel like they are guinea pigs.”

The NewsA lifesaving cancer treatment may itself cause cancers, the Food and Drug Administration reported on Tuesday.The treatment, called CAR-T, was first approved in November 2017 for life-threatening blood cancers. But, the F.D.A. said, it had received 19 reports of new blood cancers in patients who received the treatment.A composite colored scanning electron micrograph of T cells, blue, and a lymphoma cancer cell, red.Steve Gschmeissner/Science SourceA Number That Sums It Up: Thousands of lives have been saved with CAR-T.CAR-T involves removing a type of white blood cell — T cells — from a patient’s blood, then genetically engineering to make proteins — chimeric antigen receptors (CAR) — which allow the T cells to attach to cancer cells and kill them. The engineered cells are then infused back into the patient’s blood.The F.D.A. has approved six commercial CAR-T products. Cancer specialists said the treatments have saved the lives of thousands of patients with blood cancers. Even if there is a causal link between the treatments and a small risk of a new blood cancer, the regulators said on Tuesday, the benefits of the treatment outweigh the risks. That sentiment was echoed by doctors involved in cancer treatment.While the hypothetical risk was known, “we haven’t observed it” in patients, Dr. Marcela V. Maus, director of cellular immunotherapy at Massachusetts General Hospital, said.Dr. John DiPersio, director of the center for genetic and cellular immunotherapy at Washington University School of Medicine in St. Louis, said his center had treated 500 to 700 patients. And, he said, “I haven’t seen a single one” develop a new T cell cancer.CAR-T therapy has been reserved for patients who would die without it, he added.“They are all going to die and they are all going to die quickly without this treatment. It saves their life,” Dr. DiPersio said. “It works in a substantial portion of patients. The benefit is enormous.”Facts to Keep in Mind: What triggered the F.D.A.’s investigation.The F.D.A. said in its announcement that the reports of additional cancers included serious consequences — hospitalizations and deaths. And, the agency said, it is known that the way CAR-T cells are produced has a risk of causing cancers in recipients.When patients’ T cells are engineered to make proteins that attack cancer cells, a virus helps slip new genes into T cell DNA. That has the potential to disrupt other genes, leading to cancer.But there are other potential explanations. CAR-T therapy is used when patients have already had at least one round of conventional treatments with intense chemotherapy and, often, radiation. Those treatments can themselves elicit new blood cancers. Even without chemotherapy or radiation, Dr. Maus added, patients with blood cell cancers are especially susceptible to developing other blood cell cancers.What Happens Next: The search for a smoking gun.One unanswered question, Dr. Maus and Dr. DiPersio said, is whether the new cancers involved T cells carrying the added CAR proteins. That does not prove the gene insertion caused the cancers. But Dr. DiPersio said, “it is more of a smoking gun.”The F.D.A. did not describe any anticipated outcomes of its investigation but said that it was “evaluating the need for regulatory action.”

The first treatment that relies on CRISPR is expected to receive U.S. approval next month. But it may cost millions of dollars per patient.Regulators in Britain on Thursday approved the first treatment derived from CRISPR, the revolutionary gene-editing method. Called Casgevy, the treatment is intended to cure sickle-cell disease and a related condition, beta thalassemia.The manufacturers, Vertex Pharmaceuticals, based in Boston, and CRISPR Therapeutics, based in Switzerland, say about 2,000 patients in Britain with sickle-cell disease or beta thalassemia are expected to be eligible for the treatment.The companies anticipate that the Food and Drug Administration will approve Casgevy for sickle-cell patients in the United States in early December. The agency will decide on approval for beta thalassemia next year.In late December, the F.D.A. is expected to approve another sickle cell gene therapy by Bluebird Bio of Somerville, Mass. That treatment does not rely on gene editing, instead using a method that inserts new DNA into the genome.Sickle-cell disease is caused by a defective gene that leads to the creation of abnormal hemoglobin, the oxygen-carrying component in red blood cells. The cells themselves become malformed, causing episodes of extreme pain. About 100,000 Americans, who are mostly Black and Hispanic, are believed to have the illness.In beta thalassemia, the defective gene leads to deficient levels of hemoglobin in red blood cells. The condition is rare.Casgevy relies on CRISPR to nick the DNA, activating a gene that produces an alternative form of hemoglobin. To receive the sickle-cell treatment, patients in Britain must be at least 12 years old and have experienced repeated episodes of extreme pain.There is no upper age limit, nor are patients excluded because they have suffered too much organ damage from sickle-cell disease, said Dr. David Altshuler, Vertex’s chief scientific officer.But the patients must have no other options. Sickle-cell disease can be cured with a bone-marrow transplant, but few patients have compatible donors.For people struggling with the illness, the Vertex and Bluebird treatments have been a long time coming. Pain is not the only complication — people with sickle-cell disease also suffer bone and organ damage and strokes. The misshapen blood cells do not survive long, resulting in anemia.Still, the CRISPR and Bluebird treatments are onerous and will require expertise that most hospitals lack.Patients must receive intense chemotherapy to clear their bone marrow of abnormal stem cells and make room for the genetically altered cells. Then the patients must stay a month or more in a hospital while their marrow regrows.And gene editing is expensive. Vertex and CRISPR Therapeutics have not set a price yet in Britain — that will depend on conversations with those who will be paying for it, said Stuart Arbuckle, executive vice president and chief operating officer at Vertex.The price in the United States, though, is expected to be millions of dollars per patient. Sickle-cell disease itself is expensive, however, costing the U.S. health system an estimated $3 billion a year.In the United States, Bluebird already has a gene therapy approved for beta thalassemia. It costs $2.8 million per patient.Dr. Altshuler said Vertex was testing its sickle-cell treatment in children ages 5 to 11, hoping to prevent the irreversible organ damage that occurs over time.The company’s first sickle-cell patient, Victoria Gray, said on Thursday that the treatment changed her life.Ms. Gray, a Walmart associate in Forest, Miss., was diagnosed with sickle-cell disease when she was 3 months old and had a pain crisis. Those episodes became a part of her life, resulting in frequent hospitalizations.“A lot of my dreams, I couldn’t do,” she said. “The smallest things — cold, changing weather — I would end up in the hospital.”She had the gene editing treatment in 2019, when she was 33. Now, she said, all her symptoms have vanished.“It meant a new beginning,” Ms. Gray said. “It is more than I ever dreamed of, for everything to be gone.”

The NewsOn Saturday, after a 12-year effort, the Department of Veterans Affairs reached a long-term goal — it enrolled the millionth veteran in a genetic database, the Million Veteran Program.According to the V.A., the Million Veteran Program is the largest such database in the world. It includes not only genetic information but also is linked to the department’s electronic medical records and even contains records of diet and environmental exposure.The department says its data are available for now only to V.A. doctors and scientists, most of whom also have academic appointments. They have published hundreds of studies using what has already been collected.A U.S. Army veteran prepared to kayak during a Veterans Affairs health care network kayaking and sailing event on the Hudson River in August.Spencer Platt/Getty ImagesA Moment That Sums It Up: 3:46 p.m.The millionth vet joined the database on the afternoon of Nov. 11. Employees who had waited a dozen years for this moment wept.As the goal approached, the department had started an intensive email campaign, encouraging vets to sign up online or at V.A. medical centers. In the few weeks building up to the millionth vet, what had been a few hundred enrollees a day turned into thousands. The department created a ticker, which it posted online, showing the numbers.“This is a gift to the world,” said Denis McDonough, secretary of veterans affairs.The V.A. will continue to enroll more vets to the database, but this was a symbolic moment.Why It Matters: A diverse database yields disease insights.For years, researchers have been building large databases for genetic research. Using them they have found, for example, genes that appear to confer resistance to dementia and ones that most likely contribute to obesity. The discoveries provide paths to understanding these diseases and developing treatments.There are other large genetic databases, but they have mostly been built in Europe and include few minorities. The V.A. says its database offers a more diverse population: 175,000 people with African ancestry and 80,000 Hispanics joined the Million Veteran Program. The database also includes 100,000 women.“It’s a massive investment and scientific opportunity,” said Dr. Amit V. Khera, a genetic researcher at Massachusetts General Hospital. He is not a V.A. researcher, but he has used the data through collaborations with researchers who are affiliated with the department.As the database acquired participants, about 600 V.A. researchers registered to use it. The result so far has been more than 350 papers on diseases and disorders, including post-traumatic stress disorder, heart disease, high blood pressure and nonalcoholic liver disease.For example, said Dr. Sumitra Muralidhar, director of the Million Veteran Program, researchers found genes linked to having flashbacks of traumatic events, a feature of post-traumatic stress. Now, Dr. Muralidhar said, investigators can study those genes and the role they play, which may help in developing treatments for PTSD.The department also says it is being mindful of patient privacy. Although researchers can examine genetic and other data and links to medical records, fewer than 10 people at the V.A. have the links that tie records to individuals. Those records, Dr. Muralidhar said, are held at a facility in Boston that is “heavily secured.”What It Looks Like: Veterans hope the database will help.In 2019, a nurse at a V.A. hospital told Octavia Harris, 60, of San Antonio, about the Million Veteran Program. She signed up and said participating was a chance to help other vets and to help herself.Ms. Harris, who retired from the Navy in 2012 after 30 years of service, said three conditions run in her family — diabetes, high blood pressure and arthritis. She is hoping that with her genetic and health information added to that of so many others, researchers will make useful discoveries.In her family, Ms. Harris said, people died young.“We haven’t lived beyond the age of 70,” she said. “I want to go past 70.”