Gina Kolata

The new study found that patients who received drug therapy alone did not experience more heart attacks or die more often than those who also received bypass surgery or stents, tiny wire cages used to open narrowed arteries.

That finding held true for patients with several severely blocked coronary arteries. Stenting and bypass procedures, however, did help some patients with intractable chest pain, called angina.

“You would think that if you fix the blockage the patient will feel better or do better,” said Dr. Alice Jacobs, director of Cath Lab and Interventional Cardiology at Boston University. The study, she added, “certainly will challenge our clinical thinking.”

This is far from the first study to suggest that stents and bypass are overused. But previous results have not deterred doctors, who have called earlier research on the subject inconclusive and the design of the trials flawed.

Previous studies did not adequately control for risk factors, like LDL cholesterol, that might have affected outcomes, said Dr. Elliott Antman, a senior physician at Brigham and Women’s Hospital in Boston. Nor did those trials include today’s improved stents, which secrete drugs intended to prevent opened arteries from closing again.

With its size and rigorous design, the new study, called Ischemia, was intended to settle questions about the benefits of stents and bypass.

“This is an extraordinarily important trial,” said Dr. Glenn Levine, director of cardiac care at Baylor College of Medicine in Houston.

The results will be incorporated into treatment guidelines, added Levine, who sits on the guidelines committee of the American Heart Association.

The participants in Ischemia were not experiencing a heart attack, like Sen. Bernie Sanders, nor did they have blockages of the left main coronary artery, two situations in which opening arteries with stents can be lifesaving. Instead, the patients had narrowed arteries that were discovered with exercise stress tests.

With 5,179 participants followed for a median of three and a half years, Ischemia is the largest trial to address the effect of opening blocked arteries in nonemergency situations and the first to include today’s powerful drug regimens, which doctors refer to as medical therapy.

All the patients had moderate to severe blockages in coronary arteries. Most had some history of chest pain, although one in three had no chest pain in the month before enrollment in the study. One in five experienced chest pain at least once a week.

All participants were regularly counseled to adhere to medical therapy. Depending on the patient’s condition, the therapy variously included high doses of statins and other cholesterol-lowering drugs, blood pressure medications, aspirin and, for those with heart damage, a drug to slow the heart rate. Those who got stents also took powerful anti-clotting drugs for six months to a year.

Patients were randomly assigned to have medical therapy alone or an intervention and medical therapy. Of those in the intervention group, three-quarters received stents; the others received bypass surgery.

The number of deaths among those who had stents or bypass was 145, compared with 144 among the patients who received medication alone. The number of patients who had heart attacks was 276 in the stent and bypass group, compared with 314 in the medication group, an insignificant difference.

Dr. Judith Hochman, senior associate dean of clinical sciences at NYU Langone Health and chair of the study, had expected that those with the most severe chest pain and blockages would benefit from stents or bypass.

But “there was no suggestion that any subgroup benefited,” she said.

Ischemia’s results are consistent with current understanding of heart disease. Researchers have learned that a patient with a narrowed artery may have plaques not just in a single blocked area, but throughout the coronary arteries.

There is no way to predict which of those plaques will break open and cause a heart attack. Stents and bypass treat only areas that are obviously narrowed, but medical therapy treats the entire arterial system.

Yet when a cardiologist sees a blockage, the temptation for doctor and patient alike is to get rid of it quickly, said Dr. David Maron, director of preventive cardiology at Stanford University, the study’s other co-chair.

When an exercise stress test indicates a narrowing, most doctors send patients to a cardiac catheterization lab to look for blockages, Maron said. If there is a blockage, the usual practice is to open it with a stent.

If stenting is not feasible — because of the configuration of the patient’s arteries, for example — bypass surgery is usually the next step.

Patients with abnormal stress tests should talk to their doctors about the options, Maron said. If a patient has chest pain despite taking recommended medications, a stent or bypass might help improve quality of life.

Still, he said, patients have time to make considered decisions.

“You don’t have to rush to the cath lab because, OMG, you will have a heart attack soon or drop dead,” Maron said. “If you have had no angina in the last month, there is no benefit to an invasive strategy.”

Stenting costs an average of $25,000 per patient; bypass surgery costs an average of $45,000 in the United States. The nation could save more than $775 million a year by not giving stents to the 31,000 patients who get the devices even though they have no chest pain, Hochman said.

But the conventional wisdom among cardiologists is that the sort of medical therapy that patients got in Ischemia is just not feasible in the real world, said Dr. William E. Boden, scientific director of the clinical trials network at VA Boston Healthcare System, who was a member of the study’s leadership committee.

Doctors often say that making sure patients adhere to the therapy is “too demanding, and we don’t have time for it,” he said.

But getting a stent does not obviate the need for medical therapy, Boden noted. Since patients with stents need an additional anti-clotting drug, they actually wind up taking more medication than patients who are treated with drugs alone.

About a third of stent patients develop chest pain again within 30 days to six months and end up with receiving another stent, Boden added.

“We have to finally get past the whining about how hard optimal medical therapy is and begin in earnest to educate our patients as to what works and is effective and what isn’t,” Boden said.

This article originally appeared in

Surgery for Blocked Arteries Is Often Unwarranted, Researchers Find

The findings of a large federal study on bypass surgeries and stents call into question the medical care provided to tens of thousands of heart disease patients with blocked coronary arteries, scientists reported at the annual meeting of the American Heart Association on Saturday.

The drug, described in the New England Journal of Medicine, is believed to be the first “custom” treatment for a genetic disease. It is called milasen, named after the only patient who will ever take it: Mila (mee-lah) Makovec, who lives with her mother, Julia Vitarello, in Longmont, Colorado.

Mila, 8, has a rapidly progressing neurological disorder that is fatal. Her symptoms started at age 3. Within a few years, she had gone from an agile, talkative child to one who was blind and unable to stand or hold up her head. She needed a feeding tube and experienced up to 30 seizures a day, each lasting one or two minutes.

Vitarello learned in December 2016 that Mila had Batten’s disease. But the girl’s case was puzzling, doctors said. Batten’s disease is recessive — a patient must inherit two mutated versions of a gene, MFSD8, to develop the disease.

Mila had just one mutated gene, and the other copy seemed normal. That should have been sufficient to prevent the disease.

In March 2017, Dr. Timothy Yu and his colleagues at Boston Children’s Hospital discovered that the problem with the intact gene lay in an extraneous bit of DNA that had scrambled the manufacturing of an important protein.

That gave Yu an idea: Why not make a custom piece of RNA to block the effects of the extraneous DNA? Developing such a drug would be expensive, but there were no other options.

Vitarello already had set up Mila’s Miracle Foundation and was appealing for donations on GoFundMe. So, she began fundraising in earnest, eventually raising $3 million for a variety of research efforts.

Yu’s team oversaw development of the drug, tested it in rodents, and consulted with the Food and Drug Administration. In January 2018, the agency granted permission to give the drug to Mila. She got her first dose on Jan. 31, 2018.

The drug was delivered through a spinal tap, so it could reach her brain. Within a month, Vitarello noticed a difference. Mila was having fewer seizures, and they were not lasting as long.

With continued treatments, the number of seizures has diminished so much that the girl has between zero and six a day, and they last less than a minute.

Mila rarely needs the feeding tube now, and is able once again to eat puréed foods. She cannot stand unassisted, but when she is held upright, her neck and back are straight, no longer slumped.

Still, Mila has lost the last few words of her vocabulary and remains severely disabled.

“She is starting not to respond to things that made her laugh or smile,” Vitarello said.

Milasen is believed to be the first drug developed for a single patient (CAR-T cancer therapies, while individualized, are not drugs). But the path forward is not clear, Yu and his colleagues acknowledged.

There are more than 7,000 rare diseases, and more than 90% have no FDA-approved treatment, according to Rachel Sher, vice president of regulatory and government affairs at the National Organization for Rare Disorders.

Tens of thousands of patients could be in Mila’s situation in the United States alone. But there are nowhere near enough researchers to make custom drugs for all who might want them.

And even if there were, who would pay? Not the federal government, not drug companies and not insurers, said Dr. Steven Joffe, professor of medical ethics and health policy at the University of Pennsylvania.

“Unfortunately, that leaves it to families,” he added. “It feels awfully uncomfortable, but that is the reality.”

That means custom drugs would be an option only for the very wealthy, those with the skills to raise large sums of money, or those who gain the support of foundations.

Mila’s drug development was mostly paid for by the foundation run by her mother, but she and Yu declined to say how much was spent.

The idea of custom drugs also leads the FDA into uncharted territory. In an editorial published with Yu’s paper, Dr. Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, raised tough questions:

What type of evidence is needed before exposing a human to a new drug? Even in rapidly progressing, fatal illnesses, precipitating severe complications or death is not acceptable, so what is the minimum assurance of safety that is needed?

She also asked how a custom drug’s efficacy might be evaluated, and how regulators should weigh the urgency of the patient’s situation and the number of patients who could ultimately be treated. None of those questions have an easy answer.

Brad Margus, founder of the A-T Children’s Project, said he was hoping Yu would develop another custom drug for a 2-year-old girl with A-T, or ataxia telangiectasia, an extremely rare genetic disorder that causes a variety of symptoms, including problems moving, a weakened immune system and slowed mental development. Margus’ two sons have A-T.

His foundation would pay for the work, although the drug would be suitable for only one child. But Margus wondered how generalizable the custom-drug approach would be for “patients whose parents or disease advocates haven’t been lucky enough to capture a slice of Tim Yu’s time.”

Milasen will not cure Mila, Vitarello acknowledged. But Mila was 7 when she got her first dose.

“What if the next Mila is treated when she is 4 or 5?” she asked. The development of milasen “is opening up an entirely new treatment path.”

“As a mom, I still feel hopeful,” Vitarello added. “But I have one foot in hope and one foot in reality.”

Scientists Designed a Drug for Just One Patient. Her Name Is Mila

A new drug, created to treat just one patient, has pushed the bounds of personalized medicine and has raised unexplored regulatory and ethical questions, scientists reported Wednesday.

But on Monday, in a remarkable turnabout, an international collaboration of researchers produced a series of analyses concluding that the advice, a bedrock of almost all dietary guidelines, is not backed by good scientific evidence.

If there are health benefits from eating less beef and pork, they are tiny and only observed in large populations, the scientists said — not enough to tell individuals to change their meat-eating habits.

“The certainty of evidence for these risk reductions was low to very low,” said Bradley Johnston, an epidemiologist at Dalhousie University and leader of the group publishing the new research in the Annals of Internal Medicine.

The studies are among the largest nutrition evaluations ever attempted and may influence future dietary recommendations. In many ways, they raise uncomfortable questions about dietary advice and nutritional research, and what sort of standards these studies should be held to.

Already they have been met with fierce criticism by public health researchers. The American Heart Association, the American Cancer Society, the Harvard T.H. Chan School of Public Health and other groups have savaged the findings and the journal that published it.

Some called for the journal’s editors to delay publication altogether. In a statement, scientists at Harvard warned that the conclusions “harm the credibility of nutrition science and erode public trust in scientific research.”

The notion that Americans might not worry about how much red meat they eat is one of the more jarring in a series of dietary reversals over the years, involving salt, butter, fats, carbohydrates and more. And while the conclusion is likely to please proponents of popular high-protein diets, it seems certain to add to public consternation over dietary advice that seems to change every few years.

The prospect of a renewed appetite for red meat also runs counter to two other important trends: a growing awareness of the environmental degradation caused by livestock production and long-standing concern about the welfare of animals employed in industrial farming.

Beef in particular is not just another foodstuff: It was a treasured symbol of post-World War II prosperity, set firmly in the center of America’s dinner plate. But as concerns about its health effects have risen, consumption of beef has fallen steadily since the mid-1970s, largely replaced by poultry.

“Red meat used to be a symbol of high social class, but that’s changing,” said Dr. Frank Hu, chair of the nutrition department at the Harvard T.H. Chan School of Public Health in Boston. Today, the more highly educated Americans are, the less red meat they eat, he noted.

Still, the average American eats about 4 1/2 servings of red meat a week, according to the Centers for Disease Control and Prevention. Some 10% of the population eats at least two servings a day.

The new reports are based on three years of work by a group of 14 researchers in seven countries, along with three community representatives, directed by Johnston. The investigators reported no conflicts of interest and did the studies without outside funding.

In three reviews, the group looked at studies asking whether eating red meat or processed meats affected the risk of cardiovascular disease or cancer.

To assess deaths from any cause, the group reviewed 61 articles reporting on 55 populations, with more than 4 million participants. The researchers also looked at randomized trials linking red meat to cancer and heart disease (there are very few), as well as 73 articles that examined links between red meat and cancer incidence and mortality.

In each study, the scientists concluded that the links between eating red meat and disease and death were small, and the quality of the evidence was low to very low.

That is not to say that those links don’t exist. But they are mostly in studies that observe groups of people, a weak form of evidence. Even then, the health effects of red meat consumption are detectable only in the largest groups, the team concluded, and an individual cannot conclude that he or she will be better off not eating red meat.

A fourth study asked why people like red meat, and whether they were interested in eating less to improve their health. If Americans were highly motivated by even modest heath hazards, then it might be worth continuing to advise them to eat less red meat.

But the conclusion? The evidence even for this is weak, but the researchers found that “omnivores are attached to meat and are unwilling to change this behavior when faced with potentially undesirable health effects.”

Taken together, the analyses raise questions about the long-standing dietary guidelines urging people to eat less red meat, experts said.

“The guidelines are based on papers that presumably say there is evidence for what they say, and there isn’t,” said Dr. Dennis Bier, director of the Children’s Nutrition Research Center at Baylor College of Medicine in Houston and past editor of the American Journal of Clinical Nutrition.

David Allison, dean of the Indiana University School of Public Health—Bloomington, cited “a difference between a decision to act and making a scientific conclusion.”

It is one thing for an individual to believe eating less red meat and processed meat will improve health. But he said, “if you want to say the evidence shows that eating red meat or processed meats has these effects, that’s more objective,” adding “the evidence does not support it.”

Allison has received research funding from the National Cattlemen’s Beef Association, a lobbying group for meat producers.

The new studies were met with indignation by nutrition researchers who have long said that red meat and processed meats contribute to the risk of heart disease and cancer.

“Irresponsible and unethical,” said Hu, of Harvard, in a commentary published online with his colleagues. Studies of red meat as a health hazard may have been problematic, he said, but the consistency of the conclusions over years gives them credibility.

Nutrition studies, he added, should not be held to the same rigid standards as studies of experimental drugs.

Evidence of red meat’s hazards still persuaded the American Cancer Society, said Marjorie McCullough, a senior scientific director of the group.

“It is important to recognize that this group reviewed the evidence and found the same risk from red and processed meat as have other experts,” she said in a statement. “So they’re not saying meat is less risky; they’re saying the risk that everyone agrees on is acceptable for individuals.”

At the heart of the debate is a dispute over nutritional research itself, and whether it’s possible to ascertain the effects of just one component of the diet. The gold standard for medical evidence is the randomized clinical trial, in which one group of participants is assigned one drug or diet, and another is assigned a different intervention or a placebo.

But asking people to stick to a diet assigned by a flip of a coin, and to stay with it long enough to know if it affects the risk for heart attack or cancer risk is nearly impossible.

The alternative is an observational study: Investigators ask people what they eat and look for links to health. But it can be hard to know what people really are eating, and people who eat a lot of meat are different in many other ways from those who eat little or none.

“Do individuals who habitually consume burgers for lunch typically also consume fries and a Coke, rather than yogurt or a salad and a piece of fruit?” asked Alice Lichtenstein, a nutritionist at Tufts University. “I don’t think an evidence-based position can be taken unless we know and adjust for the replacement food.”

The findings are a time to reconsider how nutritional research is done in the country, some researchers said, and whether the results are really help to inform an individual’s decisions.

“I would not run any more observational studies,” said Dr. John Ioannidis, a Stanford professor who studies health research and policy. “We have had enough of them. It is extremely unlikely that we are missing a large signal,” referring to a large effect of any particular dietary change on health.

Despite flaws in the evidence, health officials still must give advice and offer guidelines, said Dr. Meir Stampfer, also of the Harvard T.H. Chan School of Public Health. He believes that the data in favor of eating less meat, although imperfect, indicate there are likely to be health benefits.

One way to give advice would be to say “reduce your red meat intake,” Stampfer said. But then, “People would say, ‘Well, what does that mean?’”

Officials making recommendations feel they have to suggest a number of servings. Yet when they do, “that gives it an aura of having greater accuracy than exists,” he added.

Questions of personal health do not even begin to address the environmental degradation caused worldwide by intensive meat production. Meat and dairy are big contributors to climate change, with livestock production accounting for about 14.5% of the greenhouse gases that humans emit worldwide each year.

Beef in particular tends to have an outsized climate footprint, partly because of all the land needed to raise cattle and grow feed, and partly because cows belch up methane, a potent greenhouse gas.

Researchers have estimated that, on average, beef has about five times the climate impact of chicken or pork, per gram of protein. Plant-based foods tend to have an even smaller impact.

Perhaps there is no way to make policies that can be conveyed to the public and simultaneously communicate the breadth of scientific evidence concerning diet.

Or maybe, said Bier, policymakers should try something more straightforward: “When you don’t have the highest-quality evidence, the correct conclusion is ‘maybe.’”

Eat Less Red Meat, Scientists Said. Now Some Believe That Was Bad Advice.

Public health officials for years have urged Americans to limit consumption of red meat and processed meats because of concerns that these foods are linked to heart disease, cancer and other ills.

Those bullets had also shredded her intestine. Tyroch hooked her up to a colostomy bag and a feeding tube. And he reached into another wound to pull out a bullet lodged in her shinbone. It had been flattened by its violent impact into a disc the size of a quarter.

The tragedy in El Paso on Saturday, carried out by a gunman armed with an AK-47-style rifle, and another deadly massacre on Sunday in Dayton, Ohio, in which the gunman used an AR-15-style pistol modified to act as a rifle, can be measured in death tolls — 22 in El Paso and nine in Dayton. But the damage done by such weapons is witnessed most clearly by members of the medical staff who care for the wounded.

The story of their lifesaving labors at the El Paso hospital, the only one in a 270-mile radius prepared to treat complex trauma patients, is one of heroics in the face of violence, and of the doctors and nurses, who, once the adrenaline rush died down, struggled to live with the horror of what they had experienced.

Tyroch spent three hours operating on the woman Sunday, repairing the damage as best he could. On Saturday, surgeons had quickly opened her abdomen, cleaned out feces and blood, and sent her, with a temporary patch over her open abdomen, to intensive care, heavily sedated and on a ventilator. They had to work fast, clearing the operating room to make way for other victims.

On Friday, six days after the shooting, doctors were still trying to repair appalling wounds in some of those who survived. The suspect in the El Paso massacre is a 21-year-old man from a Dallas suburb who told police he was targeting Mexicans.

Tyroch had seen wounds from military-style weapons before, but he had never seen anything like the number of victims that showed up at his hospital Saturday — 14 in all, most shot more than once.

The back-to-back shootings in Texas and Ohio have led to renewed calls for a ban on assault rifles from some Democratic presidential candidates. On Friday, President Donald Trump called for the passage of laws for “meaningful” background checks on gun buyers.

Many American trauma doctors maintain that assault-style weapons do not belong in civilian hands, and having far more experience with gunshot wounds than their counterparts in other countries, they have grown all too familiar with the injuries that such weapons can inflict.

“In Texas, it seems like everyone and his brother owns a gun,” said Dr. Nancy Weber, an emergency department physician at the El Paso hospital. She said she could think of no reason to own an assault rifle unless it is for a military or policing purpose. “Look at the tragedy. We should have a nationwide, nonpartisan discussion.”

For Dr. Alejandro Rios Tovar, the ordeal began Saturday at 10:55 a.m. He had just returned home from a 30-hour shift at the hospital when he got a text from Tyroch.

“Active shooter. Anybody available return to the hospital immediately.”

Tovar, a surgeon, sped to the hospital, running red lights, and pulled into the parking lot 15 minutes later.

The first patient had already arrived in a police car. A few minutes later, the ambulances began roaring in, bringing one mangled patient, then another and another.

Members of the medical staff were arriving, too, for an intense rescue effort that included four general surgeons, a cardiac vascular surgeon, three orthopedic surgeons and three surgeons in other specialties, as well as the housekeeping staff, which hurried to mop blood from floors and to clean operating rooms so patients could be wheeled in one after another.

Everyone understood the urgency. One doctor, about to leave for vacation, rushed to the hospital and operated in jeans and a T-shirt — there was no time to change into surgical scrubs.

“Trauma is a team sport,” Tyroch said. “Everyone played a role.”

Weber stabilized patients as they came in. The mnemonic that emergency room doctors use to quickly evaluate patients is ABC — airway, breathing, circulation. The critical care area of the emergency room was just steps from the operating room, allowing doctors to work so quickly that they transfused what they said was a small amount of blood, considering the injuries: 109 units, about the amount in the bodies of 11 people.

The fourth patient arrived facedown on a stretcher, “shot through and through,” said Dr. Susan McLean, a surgeon and director of surgical critical care.

Another victim’s heart had stopped, though she had received cardiopulmonary resuscitation in the ambulance. The doctors shocked her heart into beating and opened her chest to look for active bleeding.

Most victims had multiple injuries, often in the torso, with damage to the intestines and chest. Many needed tubes to drain blood from the chest or had air leaking from the lungs. Many had shattered bones in the pelvis, arms or legs.

The doctors discovered a small miracle in the carnage: No patient had a brain injury or spinal cord injury.

But one victim, shot in the chest, bled to death in the ER. The others survived, but the initial surgeries were just the beginning.

In all, 30 shooting victims were taken to University Medical Center and another hospital, Del Sol Medical Center.

“El Paso has never seen anything like this,” Weber said.

The first step for the most seriously injured was damage control: Surgeons operated only to fix the most pressing injuries, not even closing the abdomen before returning a patient to intensive care to wait for a more definitive operation the next day.

The doctors at University Medical performed eight surgeries the first day, four of which involved opening patients’ abdomens to control bleeding in areas like the intestines and diaphragms.

“We had to finish the case and get ready for the next one,” Tovar said. “And the majority of these patients are unstable. We don’t want to waste time closing the abdomen.”

On Sunday, the day after the shooting, three patients returned to general surgery to repair damage to soft tissue like muscles and to repair damage in their abdomens. Orthopedic surgeons took two more people into operating rooms, one of whom had a shattered pelvis.

As of Thursday, the operations were continuing, mostly repairs to shattered bones.

Eight patients remained in the hospital Friday, two in intensive care. One was in intermediate care, and five were on the surgical ward.

The days ahead will not be easy for patients. They risk serious complications — pneumonia, infections, blood clots.

“A complex trauma patient is a complication waiting to happen,” Tyroch said.

And the suffering doesn’t end when survivors of such shootings go home, researchers have found.

“If they leave the hospital alive, we claim we saved them,” said Dr. George Velmahos, chief of trauma surgery at Massachusetts General Hospital in Boston who was part of a team that treated victims of the Boston Marathon bombing in 2013. But years later many “still live with devastating pain or other problems, or PTSD. The long-term impact is really tremendous.”

The hospital staff will not be spared, either. As desperate patients arrived, the doctors and nurses set aside their emotions, McLean said.

The next day, as she and Tovar made rounds and spoke to patients, staff members were in tears. “It’s unreal what these patients went through,” she said. “It’s really shocking.”

Tyroch managed to maintain his composure until, driving home, he saw a familiar billboard: El Paso Strong. His emotions welled.

Weber barely made it to the privacy of her car late Saturday afternoon before the sobs came.

“There is a sense of relief when they say, ‘OK, there aren’t going to be any more victims’ — that’s the first time you take a deep breath,” she said.

“Then you go home and you cry and you pray and you hug your loved ones.”

Some of her colleagues may struggle with post-traumatic stress, Weber fears. “Doctors and nurses are not immune,” she said. “We see trauma and very traumatic deaths every day. But we don’t see 14 people in an hour, thank God.”

“What has to change?” she asked. “We have to do something. Why aren’t we?”

This article originally appeared in <a href="https://www.nytimes.com/2019/08/09/health/el-paso-hospital.html" id="46621f91-f5c1-3f58-aa4b-8b2cbc24e879">The New York Times</a>.

Surgeons Labored to Save the Wounded in El Paso Mass Shooting

The woman, grievously wounded in the mass shooting at a Walmart in El Paso, Texas, lay on an operating table at the University Medical Center of El Paso as the chief of surgery, Dr. Alan Tyroch, turned her to clean the exit wounds. He knew what to expect, but it was still a horrific sight. She had two gaping holes the size of a man’s fist in her side and a third the size of a silver dollar where bullets had burst from her body.

<h1>A half-century ago, when researchers said cancers were caused by exposure to toxins in the environment, Dr. Henry T. Lynch begged to differ.</h1>

Many cancers, he said, were hereditary. To prove his point he traveled to gatherings of families that he suspected had histories of hereditary cancer. He arranged to meet family members and asked: Who in the family had cancer? What kind of cancer? Could he get medical records, and blood samples, which he could freeze and store?

He hand-drew family trees, with squares for men and circles for women, marking who got cancer and what kind. He was soon insisting to a doubting world that he had found compelling evidence of genetic links.

In time, the medical world accepted his claims, and his work — the family trees, the blood samples — eventually contributed to the discovery, by others, of a gene that when mutated can lead to colon cancer and an array of other cancers. He also contributed work that led to the discovery of gene mutations that greatly increase the risk of breast and ovarian cancer.

Lynch died June 2 at Bergan Mercy Hospital, the main teaching hospital for Creighton University in Omaha, Nebraska, where he had spent most of his career. He was 91. His son, Dr. Patrick M. Lynch, a gastrointestinal endoscopist at MD Anderson Cancer Center in Houston, said the cause was congestive heart failure.

Henry Lynch, a 6-foot-5 former professional boxer whose physical presence belied his gentle nature, was an old-fashioned researcher who never changed his ways.

Investigators like to talk about translational research, going from bench to bedside — making discoveries in the lab and using them to treat patients. Lynch went in the opposite direction, from bedside to bench, said Dr. Funmi Olopade, director of the center of clinical cancer genetics at the University of Chicago. In Lynch’s case, though, others took over the bench part.

For years, epidemiologists dismissed Lynch’s data as anecdotal, said Dr. Steven Narod, who runs the family cancer unit at Women’s College Hospital in Toronto. Skeptics argued that the cancers Lynch saw could have occurred by chance. They included common cancers, like those of colon, breast and thyroid, which can occur in almost any family.

But some medical professionals, including Narod, were convinced even without the statistical analyses. “In 1987, I looked at those family trees and said, ‘I’m in,’” he said.

Olopade met Lynch in Omaha in 1992, when she wanted to search for breast cancer genes. Lynch offered his data.

“That day stood out in my memory,” she said. “He gave me every questionnaire, every consent.”

Dr. Judy Garber, chief of the division of cancer genetics and prevention at the Dana Farber Cancer Institute in Boston, said Lynch had helped her, too. “He was among the most decent people in academics,” she said.

Cancer researchers now estimate that 5% to 10% of cancers are inherited. Hereditary cancer syndromes, like the ones Lynch investigated, include gene mutations that predispose some to more common cancers.

One form of hereditary cancer is often called Lynch syndrome (it is also known as hereditary non-polyposis colorectal cancer, or HNPCC) because Lynch first identified families in which it occurs. People with Lynch syndrome have a higher risk of certain types of cancer.

Lynch liked to tell the story of how he got interested in cancer genetics:

When he was a medical resident, he saw a patient who was dying of colon cancer. The man began telling Lynch about all the other people in his family who had had cancer. Intrigued, Lynch applied for a research grant from the National Institutes of Health, hoping to show that colon cancer could be hereditary. He was turned down.

Undaunted, he persisted, collecting pedigrees, drawing family trees and eventually getting research grants. He mostly counseled cancer patients, advising them rather than directly caring for them, his son said.

Henry Thompson Lynch was born on Jan. 4, 1928, in Lawrence, Massachusetts, to Henry and Eleanor Lynch. He grew up poor on the Upper West Side of Manhattan. His father, a salesman, lost his job in the Depression, and his mother was a secretary.

With the onset of World War II, Henry enlisted in the Navy at age 15, using the name of a relative a few years older. He was shipped to the South Pacific as a gunner and suffered permanent hearing loss from the guns’ blasts.

When he returned from the war he earned a high school equivalency degree and became a boxer, competing under the name Hammerin’ Hank.

After a few of years of boxing professionally, he enrolled at the University of Oklahoma in Norman. After graduating in 1951, he received a master’s degree in clinical psychology from the University of Denver the next year. At the time, his son said, Lynch wanted to find the genetic roots of schizophrenia and other psychiatric disorders.

Then he decided to become a medical doctor. He later explained to his son that he had concluded that physicians had an assured income and more career options than scientists with Ph.D.s.

He earned his medical degree at the University of Texas Medical Branch in Galveston in 1960, after completing all the coursework toward a Ph.D. in human genetics at Austin.

Hired by Creighton in 1967, he stayed there because, his son said, as a serious Roman Catholic he liked being at a Jesuit institution. Lynch founded the Hereditary Cancer Center at the university in 1984.

In addition to his son, Lynch is survived by his daughters, Kathy Pinder and Ann Kelly; two brothers, Warren and Donald; 10 grandchildren; and nine great-grandchildren. His wife, Jane (Smith) Lynch, died in 2012.

Lynch was buried in a cemetery across the street from the Creighton hospital, in view of a sign on the building that says “The Henry Lynch Cancer Center.”

This article originally appeared in <a href="https://www.nytimes.com/2019/06/13/science/dr-henry-lynch-91-dies.html" target="_blank">The New York Times</a>.

He hand-drew family trees, with squares for men and circles for women, marking who got cancer and what kind. He was soon insisting to a doubting world that he had found compelling evidence of genetic links.

Dr. Henry Lynch, 91, dies; found hereditary link in cancer

The brains did not regain anything resembling consciousness: There were no signs indicating coordinated electrical signaling, necessary for higher functions like awareness and intelligence.

But in an experimental treatment, blood vessels in the pigs’ brains began functioning, flowing with a blood substitute, and certain brain cells regained metabolic activity, even responding to drugs. When the researchers tested slices of treated brain tissue, they discovered electrical activity in some neurons.

The work is very preliminary and has no immediate implications for treatment of brain injuries in humans. But the idea that parts of the brain may be recoverable after death, as conventionally defined, contradicts everything medical science believes about the organ and poses metaphysical riddles.

“We had clear lines between ‘this is alive’ and ‘this is dead,’ ” said Nita A. Farahany, a bioethicist and law professor at Duke University. “How do we now think about this middle category of ‘partly alive’? We didn’t think it could exist.”

For decades, doctors and grieving family members have wondered if it might ever be possible to restore function to a person who suffered extensive brain injury because of a severe stroke or heart attack. Were these brains really beyond salvage?

The new research confirms how little we know about the injured brain and so-called brain death. Bioethicists like Farahany were stunned and intrigued by the findings, published Wednesday in the journal Nature.

“This is wild,” said Jonathan Moreno, a bioethicist at the University of Pennsylvania. “If ever there was an issue that merited big public deliberation on the ethics of science and medicine, this is one.”

Until now, it has been assumed that the brain declines quickly when its blood supply is cut off. Cells deteriorate, and the connections between neurons crumble. Scientists have believed those changes are irreversible unless blood is quickly restored.

Researchers at Yale University acquired the heads of 32 pigs killed for their meat. The scientists sawed into the skulls and removed the brains. By the time the experiment started, the brains had been without blood and at room temperature for four hours.

The team has developed a system called BrainEx that pumps an experimental solution into the intact brain. The scientists hope the technology will help point the way to new treatments for strokes, traumatic brain injuries and diseases like Alzheimer’s.

The scientists pumped the solution into the pigs’ brains for six hours. It brought oxygen to the tissue and contained chemicals that allowed the scientists to track its flow with ultrasound.

The solution also contained chemicals intended to block nerve signals. The scientists reasoned that brain cells might be better preserved — and their metabolisms more easily restarted — if the cells were not active.

But the investigators also did not want to take a chance that the brains might regain consciousness, unlikely as that seemed. Had the team seen electrical activity suggesting actual consciousness, they planned to give the brains anesthetic drugs and cool them immediately to stop the process.

In addition to the brains that got the BrainEx solution, the scientists also examined brains that did not receive infusions and those receiving infusions of a dummy substance. Brains in both groups showed no signs of activity and their cells deteriorated.

The National Institutes of Health, which supported the research, held a briefing to discuss its significance.

“It is not a living brain, but it is a cellularly active brain,” Dr. Nenad Sestan, a neuroscientist at Yale University who led the research, said of the revived tissue.

“We wanted to test whether cells in the intact dead brain can have some functions restored,” he added.

Some people who seemed dead after prolonged exposure to cold have been resuscitated and their brains continued to function, he noted. Stroke patients who had gone as long as 16 hours with a clot blocking blood to parts of the brain have regained brain function once doctors removed the clots.

“This is a real advance,” said Andrea Beckel-Mitchener, who leads brain research efforts at the NIH. “This has never been done before in a large intact mammalian brain.”

In a study that raises profound questions about the line between life and death, researchers have restored some cellular activity to brains removed from slaughtered pigs.

Gina Kolata

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