A promo for an upcoming Fox show describes a testosterone “calamity” among American men, along with an unlikely treatment.Are you a man worried about your testosterone levels? Hoping to give them a boost? Tucker Carlson, the Fox News host, has a solution.A promotional video for a new installment in a video series by Mr. Carlson describes a “total collapse of testosterone levels in American men,” positing an explanation for what he and many conservatives see as a creeping loss of masculinity in today’s society.Chock-full of oiled, shirtless men performing vaguely masculine tasks, like turning over giant tires and throwing a javelin, the video has already been widely remarked upon on social media for its bizarre erotic imagery.But one shot in particular stands out: a naked man atop a rock pile, limbs outflung, exposing his genitals to the red light issuing from what appears to be a waist-high air purifier. Something very like the theme from “2001: A Space Odyssey” plays in the background.This is the treatment proposed by Mr. Carlson’s “documentary”: Revive your underperforming testicles with red light, in particular a device made by a little known company called Joovv.A leading endocrinologist says — no surprise — the whole thing is ridiculous, and not just because of the man receiving light therapy atop a pile of stone slabs in the dead of night.First, there is precious little evidence that testosterone “levels are declining by roughly 10 percent per decade, completely changing the way people are at the most fundamental level,” as Mr. Carlson has said.Studies examining changes in testosterone over time are challenging for several reasons, including difficulties in recruiting large populations of normal subjects, daily circadian changes in testosterone, and differences in testing methods over time, noted Dr. John Amory, an expert on male reproductive health at the University of Washington.Mr. Carlson and Fox News did not respond to requests for comment.Tied to the anxiety over testosterone is another hotly disputed assertion: that sperm counts have been declining among men in the Western world for decades. Huge numbers of studies have been done, and there is no scientific consensus on the scope of the problem or whether it exists at all.So what’s all this about bathing one’s testicles in red light?Scott Nelson, co-founder of Joovv, said in an email, “The published data around light therapy and testosterone production is pretty light, but the limited evidence is fairly compelling.” He provided a link to a study on the Joovv website, apparently unpublished, reporting that red light worked best to boost testosterone in four men who were also on a ketogenic diet.Dr. Amory was not impressed. “Obviously, doing two interventions — red light and diet — at once in a non-randomized, non-blinded, underpowered study with unclear methods isn’t of much use to understanding cause and effect,” he said. “Biological plausibility here is also very weak.”The bottom line, for readers anxious about the decline of American virility: “In the absence of any evidence of benefit from clinical trials, I wouldn’t currently recommend this as a treatment for testosterone or symptoms of low testosterone,” Dr. Amory said.“It’s notable that there is a long history of pseudoscientific treatments for low testosterone that have not proven to be useful over time,” he added.

In a yearlong study, participants who confined meals to certain hours lost no more weight than those who ate at any time.The weight-loss idea is quite appealing: Limit your eating to a period of six to eight hours each day, during which you can have whatever you want.Studies in mice seemed to support so-called time-restricted eating, a form of the popular intermittent fasting diet. Small studies of people with obesity suggested it might help shed pounds.But now, a rigorous one-year study in which people followed a low-calorie diet between the hours of 8 a.m. and 4 p.m. or consumed the same number of calories anytime during the day has failed to find an effect.The bottom line, said Dr. Ethan Weiss, a diet researcher at the University of California, San Francisco: “There is no benefit to eating in a narrow window.”The study, published on Wednesday in the New England Journal of Medicine, was led by researchers at Southern Medical University in Guangzhou, China, and included 139 people with obesity. Women ate 1,200 to 1,500 calories a day, and men consumed 1,500 to 1,800 calories daily. To ensure compliance, participants were required to photograph every bit of food they ate and to keep food diaries.Both groups lost weight — an average of about 14 to 18 pounds — but there was no significant difference in the amounts of weight lost with either diet strategy. There also were no significant differences between the groups in measures of waist circumference, body fat and lean body mass.The scientists also found no differences in such risk factors as blood glucose levels, sensitivity to insulin, blood lipids or blood pressure.“These results indicate that caloric intake restriction explained most of the beneficial effects seen with the time-restricted eating regimen,” Dr. Weiss and his colleagues concluded.The new study is not the first to test time-restricted eating, but previous studies often were smaller, of shorter duration and without control groups. That research tended to conclude that people lost weight by eating only during a limited period of time during the day.Dr. Weiss himself used to be a true believer in time-restricted eating and said that for seven years he had eaten only between noon and 8 p.m.In previous research, he and his colleagues asked some of the 116 adult participants to eat three meals a day, with snacks if they got hungry, and others were instructed to eat whatever they wanted between noon and 8 p.m. Participants lost a small amount of weight — an average of two pounds in the time-restricted eating group, and 1.5 pounds in the control group, a difference that was not statistically significant.In an interview, Dr. Weiss recalled he could hardly believe the results. He asked the statisticians to analyze the data four times, until they told him further work wouldn’t change the results.“I was a devotee,” he said. “This was a hard thing to accept.”That experiment lasted just 12 weeks. Now, it looks like even a one-year study has failed to find a benefit in time-restricted eating.Dr. Christopher Gardner, director of nutrition studies at the Stanford Prevention Research Center, said he wouldn’t be surprised if time-restricted eating nonetheless worked on occasion.“Almost every type of diet out there works for some people,” he said. “But the take-home supported by this new research is that when subjected to a properly designed and conducted study — scientific investigation — it is not any more helpful than simply reducing daily calorie intake for weight loss and health factors.”Weight-loss experts said time-restricted diets are unlikely to go away. “We don’t have a clear answer yet” about whether the strategy helps people lose weight, said Courtney Peterson, a researcher at the University of Alabama at Birmingham who studies time-restricted eating.She suspects the diet might benefit people by limiting the number of calories they have an opportunity to consume each day. “We just need to do larger studies,” Dr. Peterson said.Dr. Louis J. Aronne, director of the Comprehensive Weight Control Center at Weill Cornell Medicine in New York, said that, in his experience, some people who have trouble with calorie-counting diets do better if they are told simply to eat only during a limited period of time each day.“While that approach hasn’t been shown to be better, it doesn’t appear to be worse” than calorie counting, he said. “It gives patients more options for success.”The hypothesis behind time-restricted eating is that circadian genes that are thought to increase metabolism are turned on during daylight hours, said Dr. Caroline Apovian, co-director of the Center for Weight Management and Wellness at Brigham and Women’s Hospital in Boston.The question for researchers, she added: “If you overeat a bit during daylight hours, are you more able to burn those calories rather than store them?” Dr. Apovian said she would like to see a study that compared a group of subjects who overate all day to a time-restricted eating group of subjects who also overate.She said she would still recommend time-restricted eating to patients, she said, even though “we don’t have proof.”For Dr. Weiss, he said he was persuaded by his own study and said the new data reinforced his conviction that time-restricted eating offers no benefit.“I started eating breakfast,” he said. “My family says I am a lot nicer.”

The coronavirus pandemic hasn’t prompted most Americans to take influenza more seriously. Instead, more people are likely to think of Covid the way they think of flu, experts say.When Dr. Arnold Monto, a public health researcher at the University of Michigan, lectures about influenza, he starts by saying: “Flu is bad.”“You don’t have to start a lecture about hypertension by saying, ‘Hypertension is bad,’” he noted. It’s self-evident.But he has to convince his audiences that flu is, in fact, bad.In good years, it kills Americans in the low tens of thousands and sickens many times more. Yet even in the time of Covid, flu, the other respiratory killer caused by a virus, is underestimated. Almost half of American adults don’t bother to get vaccinated against it. Despite the ongoing Covid experience, researchers and historians don’t expect Americans’ attitudes toward flu to change much.“Statistics on flu have been given to the public; the public has been beaten to death with them for decades,” said Dr. David Morens, a flu researcher and senior adviser to the director of the National Institute of Allergy and Infectious Diseases. “And they just don’t care.”Some researchers and historians are examining attitudes toward flu for clues about how Americans will deal with Covid in the years to come. Will Covid, like flu, be a serious infectious disease that the public shrugs off even as it continues to cause large numbers of deaths each year?Public attitudes toward flu, historians and public health experts say, are revelatory — and illustrate the paradoxical thinking about risks and diseases.“It’s a story of how we get used to living with the toll of a virus and don’t count it or see it or care or fear it too much,” said Dr. Robert Aronowitz, a historian of science at the University of Pennsylvania.Americans have taken flu’s toll for granted, Dr. Morens said, despite the fact that it’s “not so far behind heart disease and cancer.”“People get excited about acute things, shocking things that happen all at once,” he said, citing Covid or Ebola or, when the disease first emerged in the 1980s, AIDS.Just over half of Americans get vaccinated against influenza. And despite the fear of respiratory viruses that Covid might have instilled, the percentage of all Americans vaccinated during this latest flu season was about the same as it was in the 2019-2020 season. It was only because of lockdowns and the avoidance of crowds and other gatherings that flu nearly disappeared last year.Rapid tests for flu are widely available, but sick patients are not often tested. Antiviral drugs help if taken soon after symptoms begin, but they are taken infrequently.“I think, for the public, ‘flu’ means minor illness,” Dr. Monto said. But in bad flu years, hospitals are filled, and elective surgeries are postponed. “People forget that,” he said.In typical flu seasons, the virus kills mostly older people and babies. But when new strains emerged, flu killed an estimated 70,000 Americans in 1957 and an estimated 100,000 in 1968. More than half of those who died in those two pandemics were under 65.Flu patients at the Naval Armory of Georgia Tech during the 1957 flu pandemic.Atlanta Journal, via Associated PressYet flu almost never shows up on death certificates, even when it is the proximate cause of death. And with little testing, the federal government is forced to use statistical manipulations to make estimates of infections and deaths that have wide error bounds. Even with those uncertainties, the Centers for Disease Control and Prevention estimates that at least 24,000 to 36,000 Americans die of flu in an average year, and nearly 100,000 die in really bad years. Most recently, in 2018, the year before the coronavirus emerged, 380,000 Americans were hospitalized with flu and an estimated 28,000 died.And that is just the tip of an iceberg. As with Covid, many get a mild respiratory disease that they do not recognize as flu or they get a symptomless flu. Unaware that they are infected, they can then spread the virus.In years like this one, when the flu vaccine was at best minimally effective, many are skeptical about getting the shots, which are widely available. Dr. Monto said there are efforts underway to produce much better flu vaccines. But, he said, because Congress is not very interested in seasonal flu, the National Institutes of Health had to tie requests for funds for flu vaccine research to pandemic preparedness.Historians say a nonchalance about flu dates back to at least the 19th century.Nancy Bristow, chair of the history department at the University of Puget Sound, looked at newspaper articles and other sources from the end of the 19th century and into the 20th century and found “a perennial refusal to pay attention to flu as a serious illness.”Flu was not frightening, Dr. Bristow said, “because it was so familiar.” It was not even a reportable disease until the 1918 pandemic.People made light of the flu in advertisements. One published in the Atlanta Constitution in 1890 said: “Kerchew! Achew!-Hew!!! Most every one has the Grippe in some form, and we would like to get Our Grip on your purchase of Furniture, Carpets, Mantels, Etc.” (Flu was once referred to as Grip or Grippe — the French word for influenza.)An ad from the Golden Eagle Clothing Company suggested a “doctor’s prescription” for a “poorly-clad boy” who “was suffering from la grippe,” writing, “The doctor has influenz-ed his mother to purchase one of those $2.50 all wool boys’ suits.”Occasionally, public health officials issued warnings. One that Dr. Bristow found was published in 1916 in the Journal of the American Medical Association. It said: “Don’t laugh at the grip. It is a deadly and dangerous thing.”The laughter stopped in 1918, when a new influenza strain caused a pandemic with a frightening mortality rate. But when that pandemic ended, Dr. Bristow said, complacency resumed. People wanted to put that awful period behind them.Margaret O’Mara, a professor of history at the University of Washington, said that even though masks were common and mandatory during the pandemic, when she looked at photographs from 1920, nobody was wearing one.Attitudes toward serious diseases are so unpredictable and inconsistent, said Tom Ewing, a flu historian at Virginia Tech.“From the perspective of a historian, this question of when diseases become noticeably significant really varies,” he said.“Why do we become fascinated and obsessed by certain diseases that are seemingly out of proportion to their effects?” Dr. Ewing asked.He does not think today’s fears of Covid will spill over into similar concern about flu. Instead, he said, attitudes toward Covid will become more like attitudes toward flu.“Historians hate to prognosticate about the future,” Dr. Bristow said. But, she said, she sees a shift in views about Covid taking place already.President Biden told the nation in his State of the Union address this month, “COVID-19 no longer need control our lives.”“It’s fascinating,” Dr. Bristow said. “We are in the process of being told how to live with something we were told to be afraid of.”He added, “We are watching the culture trying to teach us not to be terrified.”

He was able to combine pathology and biochemistry to help figure out how and why people get diseases as disparate as Alzheimer’s, Parkinson’s and A.L.S.Dr. John Q. Trojanowski, a neuropathologist whose work was at the forefront of research on Alzheimer’s and other neurodegenerative diseases, died on Feb. 8 in a hospital in Philadelphia. He was 75.His wife and longtime collaborator, Virginia M.-Y. Lee, said the cause was complications of chronic spinal cord injuries.Dr. Trojanowski “was a giant in the field,” said Leslie Shaw, a professor with Dr. Trojanowski in the department of pathology and laboratory medicine at the University of Pennsylvania — adding that he meant that in two ways.At 6 feet 4 inches, Dr. Trojanowski towered over his colleagues. And, Dr. Shaw said, he was also a towering figure in his field, whose scientific contributions were “phenomenal” because they combined pathology and biochemistry to figure out what goes wrong, and why, when people get diseases as disparate as Alzheimer’s, Parkinson’s and A.L.S. The results can lead to improved diagnosis and potential treatments.Key to the work Dr. Trojanowski did with Dr. Lee was their establishment of a brain bank: stored brains from patients with diseases like Alzheimer’s and Parkinson’s, as well as from people without degenerative brain diseases. It allowed them to compare the brains of people with and without the conditions and ask what proteins were involved in the diseases and what brain regions were affected.Among their first quests was an attempt to solve the mystery of strange areas in the brains of people with Alzheimer’s. Known as tangles and first described by Alois Alzheimer himself at the turn of the 20th century, they look like twisted strands of spaghetti in dying nerve cells. In 1991, Dr. Trojanowski and Dr. Lee determined that the regions are made up of a malformed protein called tau, which causes the structure of nerve cells to collapse.Dr. Trojanowski with his wife and longtime collaborator, Virginia M.-Y. Lee, in 2016. “It was really exciting working with John,” Dr. Lee said. “We literally spent 24/7 together.”Scott SpitzerAt a time when most Alzheimer’s researchers and drug companies were focused on a different protein, amyloid, Dr. Trojanowski and Dr. Lee insisted that tau was equally important. They then discovered that it also played a central role in a rare group of degenerative dementias known as frontotemporal lobar degeneration.The team went on to discover that another abnormal protein, alpha-synuclein, accumulates in areas known as Lewy bodies in the brains of people with Parkinson’s disease.Among their most striking discoveries was that the abnormal folding of a protein known as TDP-43 can cause what is now recognized as a common type of dementia, which is associated with profound amnesia and is often present along with Alzheimer’s disease.Dr. Trojanowski and Dr. Lee published dozens of influential papers and were among the top 10 most highly cited neuroscientists from 1997 to 2007.In an online posting of tributes by former students and colleagues, Dr. Jeffrey Kordower of Rush University Medical Center in Chicago said that Dr. Trojanowski was “the scientific light that the rest of us followed.”John Quinn Trojanowski was born in Bridgeport, Conn., on Dec. 17, 1946, the second of Margaret (Quinn) Trojanowski and Maurice Trojanowski’s seven children. Because his father was an officer in the Air Force, he spent his childhood and adolescence moving every few years among Air Force bases in the United States and Germany.After attending a long list of schools, he graduated from Notre Dame High School in Fairfield, Conn., in 1965. He majored in German studies at King’s College in Wilkes-Barre, Pa., and graduated in 1970. In 1976, he received a combined M.D.-Ph.D. degree from Tufts University.Dr. Trojanowski met Dr. Lee when she was doing postdoctoral training at Boston Children’s Hospital and he was studying at Harvard Medical School, with which the hospital is affiliated. They married in 1979 and both became faculty members at the University of Pennsylvania, where they worked as a research team.“It was really exciting working with John,” Dr. Lee said. “We literally spent 24/7 together.”Science was always on their minds, she said, a constant source of conversation, and Dr. Trojanowski had few activities outside of his work.And, she added, he never really had close friends, other than her. In part, she said, that was because he moved so often when he was growing up. But it was also because the two of them were so close.“We were very happy together,” she said. “He was pretty content just to spend his time with me.”The end of Dr. Trojanowski’s life was difficult, Dr. Lee said. He began tripping when climbing stairs, and waking in the middle of the night and wandering. After a fall the day before his birthday in December, he asked to go to the hospital, where a scan showed deep bruises pressing on his spinal cord.He had surgery twice to remove the clots but was left paralyzed and required a ventilator. He began getting infections, and every time an infection cleared he would get infected again.After three weeks of stasis, Dr. Trojanowski and Dr. Lee discussed his future.“I said, ‘You are not going into hospice care and you can’t stay here forever,’” she recalled. “‘You know you will get infections, and even if you don’t you will be paralyzed from the neck down.’”Dr. Trojanowski decided he wanted to end his life support. He asked that his ventilator tube be removed.He died two and a half hours later, Dr. Lee said.In addition to his wife, Dr. Trojanowski is survived by his brothers, John, Davis and Mark, and his sisters, Lynn Trojanowski, Annie Trojanowski and Janet Meyer.

The panel debated whether overseas trials could be applied to a more diverse U.S. population. The decision may affect other Chinese drug trials, and spotlights the high cost of immunotherapy.An advisory committee to the Food and Drug Administration overwhelmingly voted on Thursday against recommending agency approval of a lung cancer drug that was tested only in China and sold there.The drug, sintilimab, is a checkpoint inhibitor — a type of immunotherapy drug that unleashes the immune system to attack tumors. It was developed and tested in China by Innovent Biologics, which entered into an agreement with Eli Lilly that would have allowed Lilly to market it in the United States, if it were approved. It was to be used in combination with chemotherapy for patients with metastatic non-small-cell lung cancer.The F.D.A. panel debated a longstanding issue: What standards should be used in approving drugs? Should a drug tested only in China or another country outside the United States be accepted without domestic trials?The decision is likely to be closely monitored for clues about whether it further exacerbates tensions between the United States and China, especially given the strains between the two countries over research by Chinese scientists in recent years. Immunotherapy drugs are so expensive in the United States that the potential to bring a cheaper therapy to the market also weighed heavily in the background of the discussion on Thursday.Dr. Richard Pazdur, the powerful director of the F.D.A.’s oncology unit, explained on Thursday why he had backtracked from a far more welcoming attitude in 2019, when he said the agency might consider a checkpoint inhibitor tested solely in China.“Over the past two or three years, this country has experienced tremendous social change,” he said at the meeting. “We clearly heard from all patient groups that they want faces like theirs.” That, he said, is also important to build confidence in the clinical trials and the drugs being tested.A drug tested only in China is “a step backward,” he said.The agency has faced considerable pressure to include diverse patient groups, reflecting various ethnic and racial populations, in clinical trials in the United States as well as to address health disparities.Lilly released a statement saying that it was disappointed and that it had “hoped that sintilimab could have played a positive role for patients and the U.S. health care system through an aggressive pricing strategy.”But, the company said that “we acknowledge that the landscape has changed dramatically” and that Lilly “wholeheartedly agrees with the importance of ethics in clinical trial conduct and clinical trial diversity.”The company said it “will be working with FDA on next steps.”Another issue surrounded Lilly’s decision to even submit this drug for U.S. approval. An analysis by the F.D.A.’s staff of the trial results in China was scathing on methodological grounds. It cited a failure to provide patients in the control group with an approved therapy that is standard of care; questioned the competence of some of the investigators who had no previous experience with such trials; noted a patient population that was younger, had more men, and had fewer smokers than U.S. lung cancer patients; and criticized use of an endpoint that is considered not always reliable.Lilly had promoted its application by saying that it wanted to use sintilimab as a wedge to break the stratospheric prices of cancer immunotherapy.Already on the market are several other checkpoint inhibitors, which make cancers vulnerable by blocking a protein that tumors use as sort of an invisible shield to protect them from an immune system attack. These immunotherapy drugs treat such cancers as colon, breast, liver and lung, and carry list prices that are nearly identical — about $150,000 a year per patient.Lilly said it would charge 40 percent less if its drug were approved. Sintilimab costs $6,000 a year in China.The company’s idea of breaking the price lock on such drugs is “a big deal,” Brad Loncar, a biotechnology industry investor, said.“I’m not aware of any precedent of a company, especially of Lilly’s size and credibility, announcing that a discounted price like this is how they planned to innovate,” Mr. Loncar said.Now, he added, the near certainty that the drug application would be rejected “means that a real option for substantially lower drug prices is being closed in the U.S.” (The F.D.A. generally follows the recommendations of its advisory committees.)Others were not persuaded by Lilly’s claim to be a market disrupter.If approved, the drug would have been marketed in the U.S. by Eli Lilly and used in combination with chemotherapy for patients with metastatic non-small-cell lung cancer.Mike Segar/ReutersDr. Scott Ramsey, a health economist and cancer specialist at Fred Hutchinson Cancer Center in Seattle, was among those who were skeptical of Lilly’s motives. “Yeah, right,” he commented.“Are they talking about the stranglehold on prices that their current drugs contribute to?” Dr. Ramsey asked. “Maybe they could start by knocking 40 percent off their price” for Cyramza — a stomach cancer drug with a list price of $13,400.32 to $15,075.36 per month — and Verzenio, a breast cancer drug with a similar price.“I don’t buy it,” Dr. Ramsey said of Lilly’s price disrupter story, and instead chalked it up to a public relations stunt.It is well known that the F.D.A. is not permitted to consider price in evaluating whether a drug should be approved. That means that any F.D.A. decision must be based solely on whether the drug meets its standards.For that reason, Dr. Aaron Kesselheim, a professor of medicine at the Harvard T.H. Chan School of Public Health and an expert on the pharmaceutical industry, was puzzled.“I’m not aware of a company ever before announcing its pricing strategy just before an AdComm meeting, particularly one in which the general perception is that the F.D.A. was going to argue that the data don’t seem to support approval,” he said, referring to the agency’s advisory committee panel. “It does seem like a strategic ploy intended to inject a consideration into the AdComm deliberations that is not supposed to be considered.”The story of sintilimab dates to 2019 at the annual meeting of the American Association of Cancer Research. Speaking there, Dr. Pazdur said the agency would be open to considering drugs tested solely in other countries.Lilly, which had said it had not planned to market sintilimab outside China, said at the meeting that it then decided to see if the drug could be approved in the United States. The company met with the agency three times in 2020 and proceeded to apply for marketing approval.New Developments in Cancer ResearchCard 1 of 6Progress in the field.

Dr. Hultin’s discovery of a frozen victim of the 1918 pandemic gave scientists the opportunity to map the virus’s genetic material.Dr. Johan V. Hultin, a pathologist whose discovery of victims of the 1918 flu pandemic buried in Alaskan permafrost led to a critical understanding about the virus that caused the outbreak, died on Saturday at his home in Walnut Creek, Calif. He was 97.The death was confirmed by his wife, Eileen Barbara Hultin.Dr. Hultin’s discovery was crucial to finding the genetic sequence of the virus, allowing researchers to examine what made it so lethal and how to recognize it if it came again. The virus, which was 25 times more deadly than ordinary flu viruses, killed tens of millions of people and infected 28 percent of Americans, dropping the average life span in the United States by 12 years.Dr. Hultin’s quest to find victims of the 1918 flu was sparked in 1950 by an offhand remark over lunch with a University of Iowa microbiologist, William Hale. Dr. Hale mentioned that there was just one way to figure out what caused the 1918 pandemic: finding victims buried in permafrost and isolating the virus from lungs that might be still frozen and preserved.Dr. Hultin, a medical student in Sweden who was spending six months at the university, immediately realized that he was uniquely positioned to do just that. The previous summer, he and his first wife, Gunvor, spent weeks assisting a German paleontologist, Otto Geist, on a dig in Alaska. Dr. Geist could help him find villages in areas of permafrost that also had good records of deaths from the 1918 flu.After persuading the university to provide him with a $10,000 stipend, Dr. Hultin set off for Alaska. It was early June 1951.Three villages seemed like they might have what he wanted, but when he arrived at the first two, the victims’ graves were no longer in permafrost.The third village on his list, Brevig Mission, was different. The flu had devastated the village, killing 72 out of 80 Inuit residents. Their bodies were buried in a mass grave with a large wooden cross at either end.When Dr. Hultin arrived and politely explained his mission, the village council agreed to let him dig. Four days later, he saw his first victim.“She was a little girl, about 6 to 10 years old. She was wearing a dove gray dress, the one she had died in,” he recalled in an interview in the late 1990s. The child’s hair was braided and tied with bright red ribbons. Dr. Hultin called for help from the University of Alaska Fairbanks, and the group eventually found four more bodies.They stopped digging. “We had enough,” Dr. Hultin said.Dr. Hultin was a resident in surgical pathology at the Mayo Clinic in Rochester, Minn., in 1957.via Hultin familyHe removed still-frozen lung tissue from the victims, closed the grave and took the tissue back to Iowa, keeping it frozen on dry ice in the passenger compartment of a small plane.Back in the lab, Dr. Hultin tried to grow the virus by injecting the lung tissue into fertilized chicken eggs — the standard way to grow flu viruses. He was caught up in the excitement of his experiment, he said, and had not thought about the possible danger of introducing a deadly virus into the world.“I remember the sleepless nights,” he said. “I couldn’t wait for morning to come to charge into my lab and look at the eggs.”But the virus was not growing.He tried squirting lung tissue into the nostrils of guinea pigs, white mice and ferrets, but again he failed to revive the virus.“The virus was dead,” he said.Dr. Hultin never published his results but bided his time, working as a pathologist in private practice in San Francisco and hoping for another opportunity to resurrect that virus.His chance came in 1997, when, sitting by a pool on vacation with his wife in Costa Rica, he noticed a paper published in Science by Dr. Jeffery K. Taubenberger, now chief of the viral pathogenesis and evolution section at the National Institute of Allergy and Infectious Diseases.It reported a remarkable discovery. Dr. Taubenberger had searched a federal repository of pathology samples dating to the 1860s and found fragments of the 1918 virus in snippets of lung tissue from two soldiers who had died in that pandemic. The tissue had been removed at autopsy, wrapped in paraffin and stored in the warehouse.Dr. Hultin immediately wrote to Dr. Taubenberger, telling him about his trip to Alaska. He offered to return to Brevig to see if he could find more flu victims.“I remember getting that letter and thinking: ‘Gosh. This is really incredible. This is amazing,’” Dr. Taubenberger said in an interview this week. He thought the next step would be to apply for a grant for Dr. Hultin to return to Brevig. If all went well, Dr. Hultin might go back in a year or two.Dr. Hultin had a different idea.“I can’t go this week, but maybe I can go next week,” he told Dr. Taubenberger.He added that he would go alone and pay for the trip himself so that there would be no objections from funding agencies, no delays, no ethics committees and no publicity.Mrs. Hultin told her husband that the village council would never allow him to disturb the grave again. “I told him it was a fool’s errand,” she recalled on Tuesday.Dr. Hultin, though, found an ally in a council member, Rita Olanna, whose relatives had died during the flu pandemic and were buried in that grave. Her grandmother had met Dr. Hultin when he arrived in 1951. Ms. Olanna told Dr. Hultin, “My grandmother said you treated the grave with respect.”Dr. Hultin during his second trip to the Brevig Mission burial ground, in 1997.via Hultin familyHe was allowed to open the grave again. This time, four young men from the village helped him dig.At first, every body they found had decomposed. Then, toward the end of the afternoon, when the hole was seven feet deep, they saw the body of a woman that was mostly intact, with lungs that were still preserved. He extracted lung tissue and placed it in a preservative solution.After closing the grave, he made two wooden crosses to replace the original ones, which had rotted. Later, he had two brass plaques made with the names of the Brevig flu victims, which had been recorded, and returned to the village to attach them to the new crosses flanking the grave.When he returned to San Francisco, Dr. Hultin sent the lung tissue to Dr. Taubenberger in four packages — two with Federal Express, one with UPS and one more with the U.S. Postal Services’s Express Mail. He didn’t want to take any chances of losing the tissue.Dr. Taubenberger got all of the packages. The lung tissue from the Brevig woman was invaluable, he said, because the snippets of lung from the soldiers had so little virus that, with the technology at the time, the effort to get the complete viral sequence would have been delayed by at least a decade.Using the tissue Dr. Hultin provided, Dr. Taubenberger’s group published a paper that provided the genetic sequence of a crucial gene, hemagglutinin, which the virus had used to enter cells. The group subsequently used that tissue to determine the complete sequence of all eight of the virus’s genes.Dr. Hultin in 1951 at the site of a mass grave of victims of the 1918 flu pandemic.via Hultin familyJohan Viking Hultin was born on Oct. 7, 1924, into a wealthy Stockholm family. His father, Viking Hultin, had inherited an export business. When Johan was 10, his parents divorced and his mother, Eivor Jeansson Hultin, married Carl Naslund, a pathologist and virologist at the Karolinska Institute in Stockholm.He had two sisters; one died of sepsis at 6, and the other died in auto accident at 32. After high school, Johan went to Uppsala University to study medicine.He married his childhood sweetheart, Gunvor Sande, when he was completing medical school. The couple divorced in 1973, and he married Eileen in 1985.Along with his wife, Dr. Hultin is survived by his children, Peder Hultin, Anita Hultin and Ellen Swensen; three stepdaughters, Christine Peck, Karen Hill and Deborah Kenealy; 12 grandchildren; and seven great-grandchildren.Before results from the study of the Brevig woman’s virus were published, Dr. Hultin asked the villagers if they wanted the village to be identified in a news release and a journal article. They might be besieged by media. “Maybe you won’t like that,” he warned them.The Brevig residents came to a consensus: Publish the paper and identify the village. Dr. Hultin was listed as a co-author.

An inexpensive blood test can warn couples if they face one in four odds of having a baby with the disease. No one ever told Lametra Scott and Rickey Buggs about it.No doctor ever counseled Lametra Scott and her husband, Rickey Buggs, to get a simple blood test that would have warned them they each carried a mutated gene that — if inherited from both — would cause sickle cell disease in their baby.It was only after a routine blood test around week 16 of her pregnancy that she learned she had the gene. Mr. Buggs, honorably discharged from the Marines around the same time, was informed upon leaving that he, too, was a carrier.They went forward with the pregnancy, hoping their baby would be spared, but luck was not with them. Rickey, his father’s namesake, was born with sickle cell, a blood disorder that would cause him searing pain throughout a life likely to be cut short by the disease.“At that moment, my life changed forever,” said Dr. Scott, 40, a pharmacist in Nashville who is director of pharmacy for the Tennessee Department of Correction.Rickey, now 9 years old, has frequent episodes of intense pain, usually in his shins. Stiff, sickle-shaped red blood cells get caught in his blood vessels, blocking the flow, damaging their linings and causing pain because cells are deprived of oxygen-carrying blood.His mother massages his legs with oils, applies heating pads, gives him pain relievers and takes him to the hospital when the pain is unbearable, and she tries to instill him with the resolve to be strong and take each day as it comes.But she’s haunted by a question: What if she’d known before she got pregnant that her child might be born with sickle cell?About 100,000 people in the United States have the disease, which mostly affects Americans of African descent, but also people of Hispanic, Indian and Mediterranean ancestry. Yet few of the couples at risk for having babies with sickle cell know it.A person who inherits the mutated gene from just one parent has what is called sickle cell trait, not the disease itself. But if both partners in a couple have the trait, there’s a one in four chance that their baby will inherit it from both of them and have sickle cell disease.There is no routine testing of adults for the trait. Medical science is fast approaching a cure for the disease — one that would almost certainly cost more than $1 million per person — but the fractured American medical system does not ensure that parents-to-be get a simple, inexpensive blood test that would inform them if they carry the sickle cell trait.“In my view, sickle cell represents the worst and best of health care,” said Dr. Elliott Vichinsky, a sickle cell expert at the University of California, San Francisco. “We have developed new therapies and molecular testing, but people don’t get them.”Dr. Michael R. DeBaun, Rickey’s doctor, who heads a center for sickle cell treatment and research at Vanderbilt University, said that to his knowledge, “none, I mean none of the quality measures in U.S. medicine address the concept of preconception genetic counseling as a metric of standard care.”Dr. Michael DeBaun, Rickey’s doctor, says families need to be counseled on their risk of having a baby with sickle cell disease before they conceive a child.Morgan Hornsby for The New York TimesDr. Scott encourages her son, Rickey, who has sickle cell disease, to take each day as it comes.Morgan Hornsby for The New York TimesGuidelines from the American College of Obstetricians and Gynecologists say couples planning to have a baby should be tested for the sickle cell genetic mutation, but Dr. Steven Ralston, chief of obstetrics at Howard University and past chairman of the group’s committee on genetics, said testing before pregnancy was rarely done.Understand Sickle Cell DiseaseThe rare blood disorder, which can cause debilitating pain, strokes and organ failure, affects 100,000 Americans and millions of people globally, mostly in Africa.The Global Epicenter: In Nigeria, where 150,000 babies are born each year with sickle cell disease, the effects of the condition are pervasive and devastating. On the Edge of Fear: A cure for the disease, which in the United States mostly affects Black people, seems near. For some, it may come too late.Preventing Complications: A legacy of neglect toward Americans with sickle cell means that patients may not receive the treatments needed to stave off the disease’s risks. A Haunting Memory: The Times reporter Gina Kolata shares her experience reporting on the inequities in access to medical advances in the treatment of the disease.“Part of it is an educational problem,” he said. “The guideline hasn’t trickled down to people.”The U.S. Preventive Services Task Force, an independent panel of experts that advises the federal government on screening tests and services to prevent disease, has never considered sickle cell. The chairman of the task force until last spring, Dr. Doug Owens, chairman of the department of health policy in the Stanford University School of Medicine, explained in an interview that it studies only diseases nominated for consideration by a member of the public. Yet, though screening for sickle cell trait “is a very important topic,” Dr. Owens said, it had never been nominated.Sickle cell experts say what happened to Dr. Scott and Mr. Buggs was an outrage that is still all too common.Dr. Scott’s obstetrician suggested the couple see a genetic counselor well into her pregnancy, after learning they both had the sickle cell trait. Dr. Scott declined. She was in the medical field and believed she had only two options — to continue the pregnancy or have prenatal testing and abort if the baby had the disease. She and Mr. Buggs decided to take a chance.Their lives would have been so different, she said, had they known they were carriers of the trait before she got pregnant. They could have chosen to adopt or not to have children.And there was a third choice: preimplantation genetic diagnosis. Her eggs would have been removed from her ovaries and fertilized with her husband’s sperm. But only embryos that did not carry the mutation would have been implanted in her womb.The procedure typically costs tens of thousands of dollars out of pocket. Yet the lifelong costs of medical care for a person with sickle cell are over $2 million, according Dr. Scott Ramsey of the Fred Hutchinson Cancer Research Center, whose federally funded study of the costs of sickle cell care is now under review at a medical journal.“I would have had preimplantation genetic diagnosis,” Dr. Scott said, “hands down.”How Can I Help My Child?Dr. Scott and Mr. Buggs were in shock when they learned their baby had the disease. She turned to Facebook, looking for support groups.“People were always in the hospital, always dying,” she said. “My baby is only a couple of months old. Is this what is going to happen to him?”“I started praying really, really hard,” she said.She and her husband have devoted themselves to caring for Rickey. Sickle cell is a way of life for him — he can’t even remember when he first realized he had it. His mother coaches him to live each day as it comes.“I tell him, ‘You can be your own spokesperson and tell your own story,’” she said. “If your mind is in the right place, you can get through everything,”“I can still have fun,” Rickey said on a recent Sunday afternoon.Rickey’s passion is video games He recently wore a shirt that bore a slogan: Due to Video Games, Sleep is Canceled. Morgan Hornsby for The New York Times“I can still have fun,” Rickey says. He attends an after-school program at Boost Gymnastics in Nashville.Morgan Hornsby for The New York TimesHis passion is video games. His shirt bore a slogan: Due to Video Games, Sleep is Canceled. He patiently sat through an interview, waiting for the moment when he could run upstairs and play Fortnite.His parents want Rickey to have a normal childhood, but after consulting with Dr. DeBaun they decided soccer was too risky. He wanted to swim, so Dr. Scott found places with heated pools and bought him a wet suit because cold can bring on pain crises.His parents hope he will be free of sickle cell one day.“I know that in his lifetime there will be a cure,” Ms. Scott said. “I am praying it will be before he turns 21.”A Fraught History of RacismIt sounds so obvious. Why not just test all adults for the sickle cell trait? But it’s anything but simple. In the United States, Black people with the trait have faced discrimination.As recently as the early 1980s, people with the trait were barred from the Air Force Academy and charged much higher rates for life insurance.Even Linus Pauling, who famously discovered that sickle cell was caused by the substitution of a single amino acid in the globin protein, was part of this dismal history. He proposed that young people with the trait have that information tattooed on their foreheads, saying he wanted to make sure they were identified and choose not to have children or to have abortions if their baby would have sickle cell.“Genetic counseling, difficulties with insurance coverage, and employment restrictions raised the specter of discrimination, racism and even accusations of genocide,” said Keith Wailoo, a historian at Princeton University.The fraught history of the disease in the United States has complicated efforts to devise a public health strategy to test and inform those who have the trait.Routine genetic tests of newborns detect not just sickle cell disease but also sickle cell trait. If a baby has the trait, that means at least one parent has the mutation. Both parents should be counseled and tested to see if future children are at risk of having sickle cell disease.But it is up to each state to decide what to do with the newborn screening results. Practices vary — greatly.Most states’ guidelines say the baby’s pediatrician should be told if the child has sickle cell trait — but the information chain can end there.Often, especially in big cities, said Dr. Kwaku Ohene-Frempong, president of the Sickle Cell Foundation of Ghana and an emeritus professor at the University of Pennsylvania, the baby is cared for in a public health clinic with no assigned pediatrician at birth. Test results are noted in the mother’s chart, with no follow-up.And despite the guidelines, pediatricians may not be informed, said Mary Brown, president of the California Sickle Cell Disease Foundation. The test results “might just sit on a shelf,” she said.The Black Panthers made a push in the 1970s to raise awareness about sickle cell disease in Black communities. In 1972, they held a sickle cell testing drive at the Civic Auditorium in San Francisco.Dave Randolph/San Francisco Chronicle via Getty ImagesThere was a moment in the early 1970s when the Black Panthers made sickle cell part of their drive to improve health care for Black people. Testing was controversial but, noted Dr. Wailoo, the Panthers emphasized Black pride and self-sufficiency. Testing for sickle cell trait fit their mission, along with tests for high blood pressure and elevated levels of lead in the blood.Bobby Seale, Black Panthers chairman in 1970, instructed the group’s chapters to open health care clinics. There was a major effort in Oakland, Calif., staffed by volunteers, doctors and nurses. Clinics were held on the streets in good weather and in Panthers offices when it was bad, said Jamal Joseph, a former Panthers lmember who is now a professor of professional practice at Columbia University School of the Arts.The volunteers counseled people who had the trait that “if they were dating or married that should be something they should consider,” Professor Joseph said.That focus on sickle cell disease is long gone, Dr. Vichinsky noted.In California, for example, the state asks the pediatrician in the hospital to inform the family their baby has the sickle cell trait and to provide contacts for the Sickle Cell Disease Foundation of California, the only group authorized to provide counseling. Then, said Deborah Green, a program administrator at the foundation, “it is on the parent to follow up.” The state’s confidentiality laws prohibit the foundation from contacting the parents.“The assumption is that people who get the letter understand the letter,” Ms. Green said. “People may not even get the letter.”Dr. Richard Olney, head of the foundation’s genetic disease screening program, said that when parents do not contact the Sickle Cell Disease Foundation, the state sends a second letter telling them again that their baby has sickle cell trait and, once again, giving them the telephone number for the Sickle Cell Disease Foundation of California.But, he said, only about 10 to 15 percent of the 5,000 families notified each year call for counseling.‘I Feel Like It’s a Ministry’She got the idea from the mother of Rickey’s best friend, who asked her: Have you ever thought about forming a sickle cell foundation?That passing suggestion got Dr. Scott thinking about how she could help people learn from her and her husband’s experiences, both about the need to get screened for the sickle cell trait before conceiving a child and the full range of choices if both partners carried the mutation.And so in 2015 she started a nonprofit, Breaking the Sickle Cell Cycle. Her husband, a technology consultant, helped her plan and market events.“You never know what you can do until you jump in and do it,” Dr. Scott said.It’s an all-volunteer effort run on a shoestring, and she takes little Rickey with her whenever she can. She visits churches, colleges, schools and health fairs to spread the word.Dr. Scott said she recognized her foundation’s limitations, but cherished small victories.She raised money to help a woman caring for her 14-year-old nephew who had sickle cell. He wet his bed at night because sickle cell damaged his kidneys. His aunt did not have a washer or dryer and “was washing sheets all the time,” Dr. Scott said.Dr. Scott got the family supplies of Depends, sheets and cleaning items.Dr. Scott prepared Rickey’s medicine on a recent evening at home.Morgan Hornsby for The New York TimesAttending a virtual support meeting for people living with sickle cell disease and their caregivers.Morgan Hornsby for The New York TimesDr. DeBaun, Rickey’s doctor, calls Dr. Scott “an army of one.”“The effort is important,” he said. “But it’s a lonely job for a mother focused on changing health care delivery for a rare disease, particularly a rare disease that disproportionally affects African Americans.”Dr. Scott regularly takes her son, Rickey, with her on her travels to educate the public.“People think it’s all gloom and doom,” she said. “I want him to be an advocate and to speak up and encourage others in his own little way.”“I feel like it’s a ministry,” she said. “If I only make a difference in one person’s life, I will have changed a whole generation.”

By tracking every cell in an organism, scientists are working out why certain cancer treatments fail, which could lead to improved medicine.No one really knew why some patients with a white blood cell cancer called chronic lymphocytic leukemia, or CLL, relapsed after treatment and got a second cancer. Were some cancer cells just resistant?An unexpected answer to this mystery has been found using a new technique that researchers call bar coding: The treatment does not always target the right cells.Scientists discovered that the cancer does not always originate in the mature bone marrow cells where it is found and where textbooks say it originates. Instead, for some patients, the mother lode of the cancer can be primitive bone marrow cells, the stem cells, that give rise to all of the body’s white and red blood cells. Those cells, not affected by the chemotherapy treatment, can spawn new cancer cells, causing a relapse.The discovery is one early fruit of the bar coding method, which is aiding the study of the origins of cancer and other diseases. The results are too new to have led to patient therapies. But they are leading to provocative discoveries that are expected to inspire novel methods for treating diseases.The method works by marking individual cells with a stamp that is passed on to all of a cell’s progeny. Researchers can look at a cell, note its bar code and trace its lineage back to its parents, grandparents, great-grandparents — all the way back to its origins — because each cell that arose from the original bar coded cell has the same stamp.The idea for bar coding during embryonic development originated with Dr. Jay Shendure and his colleagues at the University of Washington, and this class of methods was anointed the breakthrough of the year by Science magazine in 2018. Now there is a variety of methods for bar coding ranging from embryo cells to cancer cells to mature cells.For example, Dr. Shendure and another group of colleagues at the University of Pennsylvania are using bar codes in mice with pancreatic cancer to study the spread of cancer cells in their bodies.In the case of CLL above, Dr. Vijay Sankaran at Boston Children’s Hospital and his colleagues bar coded human cancer cells by taking advantage of innocuous, naturally occurring mutations that mark individual cells and are inherited by their progeny.Bar coding, Dr. Sankaran said, “starts to give us a view of cancer that we never had before.”The technique also revealed a surprising result to Dr. Leonard Zon of Harvard Medical School. He wanted to study clonal hematopoiesis of uncertain potential, or CHIP, a common but poorly understood condition that is common in older people and increases the risk for cancer and heart disease. CHIP occurs when the progeny of a single blood stem cell take over all or a large part of the bone marrow, squeezing out other stem cells.To investigate, Dr. Zon marked individual marrow stem cells with different colors in tiny, transparent zebrafish. The result resembled what happens in patients — by the time the fish were adults, half of their blood cells were a single color, meaning they were derived from a single stem cell.But how did one cell take over?The answer was a surprise. The dominant cells secreted toxic inflammatory proteins. Those proteins suppressed the growth of other stem cells and injured the environment where the marrow cells grow. But the stem cell parents survived and kept generating new toxin-secreting progeny.The group also found a gene in the mutant cells that allowed them to be resistant to the inflammation. When they blocked that gene, the mutant cells could no longer take over.Fernando Camargo, a stem cell biologist at Boston Children’s, addressed a different problem — why are standard cancer treatments that transplant healthy bone marrow stem cells from donors so difficult, often leaving patients vulnerable to severe infections?When he and his colleagues bar coded marrow cells in mice by genetically marking them with the gene-editing technique known as CRISPR, he discovered that the cells everyone called stem cells were not the main contributors to blood production.“We always assumed those are the same cells that normally give rise to all of your blood,” Dr. Camargo said.Instead, a different set of cells, which he calls progenitor cells, give rise to most blood in living animals. In a stem cell transplant, both progenitor cells and the putative stem cells are transplanted, but the progenitor cells quickly die off in the new environment.Now the question is: Why don’t the progenitor cells survive transplant? It could be that the strong doses of radiation and chemotherapy that clear out the marrow for a transplant make the marrow inhospitable. Or it could be that the progenitor cells, injected with stem cells into blood, can’t find their way to the marrow.Dr. Camargo is left shaking his head.“We thought we knew everything about blood stem cells,” he said. “Obviously, we didn’t.”

A new treatment using stem cells that produce insulin has surprised experts and given them hope for the 1.5 million Americans living with the disease.Brian Shelton’s life was ruled by Type 1 diabetes.When his blood sugar plummeted, he would lose consciousness without warning. He crashed his motorcycle into a wall. He passed out in a customer’s yard while delivering mail. Following that episode, his supervisor told him to retire, after a quarter century in the Postal Service. He was 57.His ex-wife, Cindy Shelton, took him into her home in Elyria, Ohio. “I was afraid to leave him alone all day,” she said.Early this year, she spotted a call for people with Type 1 diabetes to participate in a clinical trial by Vertex Pharmaceuticals. The company was testing a treatment developed over decades by a scientist who vowed to find a cure after his baby son and then his teenage daughter got the devastating disease.Mr. Shelton was the first patient. On June 29, he got an infusion of cells, grown from stem cells but just like the insulin-producing pancreas cells his body lacked.Now his body automatically controls its insulin and blood sugar levels.Mr. Shelton, now 64, may be the first person cured of the disease with a new treatment that has experts daring to hope that help may be coming for many of the 1.5 million Americans suffering from Type 1 diabetes.“It’s a whole new life,” Mr. Shelton said. “It’s like a miracle.”Diabetes experts were astonished but urged caution. The study is continuing and will take five years, involving 17 people with severe cases of Type 1 diabetes. It is not intended as a treatment for the more common Type 2 diabetes.“We’ve been looking for something like this to happen literally for decades,” said Dr. Irl Hirsch, a diabetes expert at the University of Washington who was not involved in the research. He wants to see the result, not yet published in a peer-reviewed journal, replicated in many more people. He also wants to know if there will be unanticipated adverse effects and if the cells will last for a lifetime or if the treatment would have to be repeated.But, he said, “bottom line, it is an amazing result.”Dr. Peter Butler, a diabetes expert at U.C.L.A. who also was not involved with the research, agreed while offering the same caveats.“It is a remarkable result,” Dr. Butler said. “To be able to reverse diabetes by giving them back the cells they are missing is comparable to the miracle when insulin was first available 100 years ago.”And it all started with the 30-year quest of a Harvard University biologist, Doug Melton.‘A Terrible, Terrible Disease’Dr. Melton had never thought much about diabetes until 1991 when his 6-month-old baby boy, Sam, began shaking, vomiting and panting.“He was so sick, and the pediatrician didn’t know what it was,” Dr. Melton said. He and his wife Gail O’Keefe rushed their baby to Boston Children’s Hospital. Sam’s urine was brimming with sugar — a sign of diabetes.The disease, which occurs when the body’s immune system destroys the insulin-secreting islet cells of the pancreas, often starts around age 13 or 14. Unlike the more common and milder Type 2 diabetes, Type 1 is quickly lethal unless patients get injections of insulin. No one spontaneously gets better.“It’s a terrible, terrible disease,” said Dr. Butler at U.C.L.A.Dr. Doug Melton, a biologist at Harvard University, did not think much about diabetes until his 6-month-old son started showing symptoms.Kayana Szymczak for The New York TimesPatients are at risk of going blind — diabetes is the leading cause of blindness in this country. It is also the leading cause of kidney failure. People with Type 1 diabetes are at risk of having their legs amputated and of death in the night because their blood sugar plummets during sleep. Diabetes greatly increases their likelihood of having a heart attack or stroke. It weakens the immune system — one of Dr. Butler’s fully vaccinated diabetes patients recently died from Covid-19.Added to the burden of the disease is the high cost of insulin, whose price has risen each year.The only cure that has ever worked is a pancreas transplant or a transplant of the insulin-producing cell clusters of the pancreas, known as islet cells, from an organ donor’s pancreas. But a shortage of organs makes such an approach an impossibility for the vast majority with the disease.“Even if we were in utopia, we would never have enough pancreases,” said Dr. Ali Naji, a transplant surgeon at the University of Pennsylvania who pioneered islet cell transplants and is now a principal investigator for the trial that treated Mr. Shelton.Blue CluesFor Dr. Melton and Ms. O’Keefe, caring for an infant with the disease was terrifying. Ms. O’Keefe had to prick Sam’s fingers and feet to check his blood sugar four times a day. Then she had to inject him with insulin. For a baby that young, insulin was not even sold in the proper dose. His parents had to dilute it.“Gail said to me, ‘If I’m doing this you have to figure out this damn disease,” Dr. Melton recalled. In time, their daughter Emma, four years older than Sam, would develop the disease too, when she was 14.Dr. Melton had been studying frog development but abandoned that work, determined to find a cure for diabetes. He turned to embryonic stem cells, which have the potential to become any cell in the body. His goal was to turn them into islet cells to treat patients.One problem was the source of the cells — they came from unused fertilized eggs from a fertility clinic. But in August 2001, President George W. Bush barred using federal money for research with human embryos. Dr. Melton had to sever his stem cell lab from everything else at Harvard. He got private funding from the Howard Hughes Medical Institute, Harvard and philanthropists to set up a completely separate lab with an accountant who kept all its expenses separate, down to the light bulbs.Over the 20 years it took the lab of 15 or so people to successfully convert stem cells into islet cells, Dr. Melton estimates the project cost about $50 million.Mr. Shelton’s diabetes treatment supplies. He said his new drugs, which suppress his immune system, are far less onerous than the constant blood sugar monitoring and insulin intake.Amber Ford for The New York TimesThe challenge was figure out what sequence of chemical messages would turn stem cells into insulin-secreting islet cells. The work involved unraveling normal pancreatic development, figuring out how islets are made in the pancreas and conducting endless experiments to steer embryonic stem cells to becoming islets. It was slow going.After years when nothing worked, a small team of researchers, including Felicia Pagliuca, a postdoctoral researcher, was in the lab one night in 2014, doing one more experiment.“We weren’t very optimistic,” she said. They had put a dye into the liquid where the stem cells were growing. The liquid would turn blue if the cells made insulin.Her husband had already called asking when was she coming home. Then she saw a faint blue tinge that got darker and darker. She and the others were ecstatic. For the first time, they had made functioning pancreatic islet cells from embryonic stem cells.The lab celebrated with a little party and a cake. Then they had bright blue wool caps made for themselves with five circles colored red, yellow, green, blue and purple to represent the stages the stem cells had to pass through to become functioning islet cells. They’d always hoped for purple but had until then kept getting stuck at green.The next step for Dr. Melton, knowing he’d need more resources to make a drug that could get to market, was starting a company.Moments of TruthHis company Semma was founded in 2014, a mix of Sam and Emma’s names.One challenge was to figure out how to grow islet cells in large quantities with a method others could repeat. That took five years.The company, led by Bastiano Sanna, a cell and gene therapy expert, tested its cells in mice and rats, showing they functioned well and cured diabetes in rodents.At that point, the next step — a clinical trial in patients — needed a large, well financed and experienced company with hundreds of employees. Everything had to be done to the exacting standards of the Food and Drug Administration — thousands of pages of documents prepared, and clinical trials planned.Chance intervened. In April 2019, at a meeting at Massachusetts General Hospital, Dr. Melton ran into a former colleague, Dr. David Altshuler, who had been a professor of genetics and medicine at Harvard and the deputy director of the Broad Institute. Over lunch, Dr. Altshuler, who had become the chief scientific officer at Vertex Pharmaceuticals, asked Dr. Melton what was new.Dr. Melton took out a small glass vial with a bright purple pellet at the bottom.“These are islet cells that we made at Semma,” he told Dr. Altshuler.Vertex Pharmaceuticals’ headquarters in Boston.Bill Sikes/Associated PressVertex focuses on human diseases whose biology is understood. “I think there might be an opportunity,” Dr. Altshuler told him.Meetings followed and eight weeks later, Vertex acquired Semma for $950 million. With the acquisition, Dr. Sanna became an executive vice president at Vertex.The company will not announce a price for its diabetes treatment until it is approved. But it is likely to be expensive. Like other companies, Vertex has enraged patients with high prices for drugs that are difficult and expensive to make.Vertex’s challenge was to make sure the production process worked every time and that the cells would be safe if injected into patients. Employees working under scrupulously sterile conditions monitored vessels of solutions containing nutrients and biochemical signals where stem cells were turning into islet cells.Less than two years after Semma was acquired, the F.D.A. allowed Vertex to begin a clinical trial with Mr. Shelton as its initial patient.Like patients who get pancreas transplants, Mr. Shelton has to take drugs that suppress his immune system. He says they cause him no side effects, and he finds them far less onerous or risky than constantly monitoring his blood sugar and taking insulin. He will have to continue taking them to prevent his body fro rejecting the infused cells.But Dr. John Buse, a diabetes expert at the University of North Carolina who has no connection to Vertex, said the immunosuppression gives him pause. “We need to carefully evaluate the trade-off between the burdens of diabetes and the potential complications from immunosuppressive medications.”Mr. Shelton’s treatment, known as an early phase safety trial, called for careful follow-up and required starting with half the dose that would be used later in the trial, noted Dr. James Markmann, Mr. Shelton’s surgeon at Mass General who is working with Vertex on the trial. No one expected the cells to function so well, he said.“The result is so striking,” Dr. Markmann said, “It’s a real leap forward for the field.”Mr. Shelton recalls shedding tears when he checked his blood sugar levels after having a meal following his procedure.Amber Ford for The New York TimesLast month, Vertex was ready to reveal the results to Dr. Melton. He did not expect much.“I was prepared to give them a pep talk,” he said.Dr. Melton, normally a calm man, was jittery during what felt like a moment of truth. He had spent decades and all of his passion on this project. By the end of the Vertex team’s presentation, a huge smile broke out on his face; the data were for real.He left Vertex and went home for dinner with Sam, Emma and Ms. O’Keefe. When they sat down to eat, Dr. Melton told them the results.“Let’s just say there were a lot of tears and hugs.”For Mr. Shelton the moment of truth came a few days after the procedure, when he left the hospital. He measured his blood sugar. It was perfect. He and Ms. Shelton had a meal. His blood sugar remained in the normal range.Mr. Shelton wept when he saw the measurement.“The only thing I can say is ‘thank you.’”

Colin Powell, the first Black secretary of state, had multiple myeloma. The form of blood cancer hobbles the immune system and makes vaccines, including those for Covid-19, largely ineffective.It is a cancer that attacks plasma cells, which build the antibodies essential to the body’s immune defenses. It also lives in the bone marrow, crowding out the spongy material in the middle of bones and preventing healthy plasma cells from being made. In addition to weakening the immune system, the cancer can also lead to kidney damage.Multiple myeloma seems to emerge as random bad luck for those who develop the disease, and scientists cannot yet predict it based on genetic or environmental factors. But there are risk factors and Mr. Powell had them. Being Black doubles the risk, as does being male. Nearly all multiple myeloma patients are over age 45. Mr. Powell was 84.But it is a rare cancer, accounting for just 1.8 percent of cancers in the United States with 34,920 new cases a year, according to the National Cancer Institute, a rate that has remained stable for the past decade.The cancer’s five-year survival rate is 55.6 percent, which has barely declined over the past decade despite the introduction of more sophisticated drugs. About 12,410 deaths per year, or 2 percent of national cancer deaths, are the result of multiple myeloma.There’s no known way to prevent the disease.Patients in the early stages of multiple myeloma may not notice any symptoms — their disease might be detected in a routine blood or urine test. Later, when the disease is more advanced, patients may experience bone pain, fevers or frequent infections, as well as exhaustion, trouble breathing and weakness in their arms or legs. Their skin might easily bruise, and their bones might easily break.Treatments include chemotherapy and radiation and stem cell transplants, in which the cells in a person’s bone marrow are deliberately destroyed and new cells are infused to repopulate the marrow. Those replacement cells could be the patient’s own blood-forming marrow cells, removed and stored before the marrow is destroyed, or they could be cells from a closely related donor. Stem cell transplants with the patient’s own cells can put the disease into remission, but it eventually returns.The Food and Drug Administration recently approved a newer treatment designed to directly attack the cancer by harnessing the T cells of the patient’s own immune system or by using drugs designed to block particular molecules on the cancer cell surfaces.