Matt Richtel

Millions of people now inhale marijuana not from joints or pipes filled with burning leaves but through sleek devices and cartridges filled with flavored cannabis oils. People in the legalized marijuana industry say vaping products now account for 30% or more of their business. Teenagers, millennials and baby boomers alike have been drawn to the technology — no ash, a faint smell, easy to hide — and the potentially dangerous consequences are only now becoming evident.

Most of the patients in the outbreak of severe lung illnesses linked to vaping — which has left 1,479 people sick and 33 dead so far — vaped THC, the ingredient in marijuana that makes people high. Until more information is known, officials at the Centers for Disease Control and Prevention have warned people not to vape cannabis products.

To some scientists, and even industry leaders, warning signs have been apparent for years as vaping cannabis grew in the shadows, propelled by a patchwork of regulations, a wave of state-by-state legalization and a soaring supply of low-cost marijuana.

While the government and researchers poured resources into studying e-cigarettes, federal rules sharply limiting research into the health effects of cannabis — because it is classified as a controlled substance with a high potential for abuse — have left a void in scientific knowledge about what THC vaping does to the lungs.

Last year, Dr. Neal Benowitz, a professor of medicine and a researcher on nicotine and vaping at the University of California, San Francisco, sent a letter to Congress warning of the risks posed by leaving a hugely popular practice unstudied.

“Very little is known about the safety or effects of vaped cannabis oil,” he wrote, cautioning that some ingredients mixed into the oils “could have harmful, toxic effect on users, including the potential for causing and/or promoting cancer and lung disease.”

“It’s disgraceful,” Benowitz said in a recent interview as reports of hospitalizations and deaths from vaping-related lung illnesses mounted. “I’m not able to take products we think are potentially harmful and do analysis. I can buy a vape device around the corner, but I can’t bring it into the lab and test it.”

Even members of the legalized marijuana industry acknowledge the lack of hard science about the cannabis vaping products they sell.

“There’s a glaring gap in trying to understand this product,” said Jerred Kiloh, president of the board of the United Cannabis Business Association, which represents 165 marijuana dispensaries in California, where marijuana was legalized for recreational use in 2016.

Kiloh, who owns the Los Angeles dispensary Higher Path, said he believed that the vape pens sold in his stores and in other licensed and regulated stores are likely safe because the ingredients were measured and tested by the state. The state Bureau of Cannabis Control did not return calls asking for comment.

Vaping oils typically include other additives, solvents and flavor enhancers, and health investigators believe some such ingredients, including vitamin E acetate, could be responsible for some of the lung illness cases. The problem of unknown and potentially dangerous additives, Kiloh and others said, is vastly worse in a soaring black market in the nearly 40 states where recreational marijuana is still illegal.

Even in states where the drug is legal, counterfeit cartridges are cheaper than the licensed, tested and taxed products. It is hard for legal players who pay taxes to compete. A regulated vape pen with half a gram of THC costs $55, compared with $25 or less on the street for an untested product.

“We don’t know what the chemical composition is,” Kiloh said, “and we especially don’t know what the chemical composition is once it’s been combined, heated and inhaled.”

No Ash, No Rolling Papers

In the earliest days of cannabis vaping, a small group of innovators saw the technology as a safer way to help medicinal marijuana patients. They hoped that vaping — which entails heating THC so that it turns to an aerosol — would be less harmful to the lungs than inhaling combusted marijuana.

But that ethos quickly gave way to a different lure: the pure convenience of vaping, which allowed users to avoid rolling joints, spilling ash, giving off a telltale smell — or getting caught. Vape pens brought the sheen of high technology to a drug associated with hippies and grunge, along with the discretion of, say, texting beneath the dinner table.

“You could vape in a police station and no one would even know, not that you’d want to do that,” said a 35-year-old man outside Harvest, a marijuana dispensary in San Francisco, who declined to give his name because he said he did not want to hurt his job-hunting prospects.

Other Harvest customers said they once embraced vaping but now have doubts. “It’s convenient, neat, easy. No lighter,” said Michael, who, with his wife, Laurie, both in their 70s, declined to give a last name because they didn’t want their teenage granddaughter to know about their habit.

With news of vaping-related hospitalizations and deaths, though, Laurie was growing concerned. So this time she came to Harvest to buy flower, the old-fashioned bud rolled in joints. It was a switch the couple said they would continue while they await more vaping science.

Others were undeterred. Cynthia Valdivia, 34, bought a THC vape cartridge after using one to try marijuana for the first time this summer. She said she was not worried about what she bought from a legal store.

“There’s someone behind the brand, and they don’t want to kill people,” she said. “They want their money.”

The market has flourished in the absence of regulation, said Eric N. Lindblom, a former tobacco official at the Food and Drug Administration. The federal government, he said, has been unsure of how to respond to state legalization of marijuana, and the uncertainty has left a void of regulation, research and enforcement.

“Only now that we have this special, extra weird mystery crisis with the disease and deaths is there now interest in doing something,” he said.

“The market has run amok,” said Carlos de la Torre, the owner of Cornerstone Wellness, a dispensary in Los Angeles.

De la Torre came to the cannabis business in 2007 after a career in television advertising. That year he opened his shop in a Los Angeles suburb, selling marijuana flower and edibles to customers with medical cards.

“At the time, I don’t think vaping really existed,” he said.

Not commercially, at least. There was a rich and informal history among a narrow band of regular marijuana users who bathed weed in alcohol to extract THC — so-called honey oil or hash oil. That was the domain of the “biker, LSD, hippie crowd,” said David Downs, the California bureau chief of Leafly, a cannabis news and product website.

The first commercial marijuana vaping brand was called the Volcano, and it was the brainchild of a German entrepreneur, Markus Storz, who obtained a patent for it from his native country in 1999.

The Volcano came to the United States in 2003, and it is aptly named. It is built on a sturdy, triangular-shaped base — “the kind of thing that sat on a coffee table and weighed a pound,” de la Torre said.

It heated marijuana flower until the THC baked off as vapor. A user then inhaled the aerosol from a large plastic bag attached to an inhalation pipe.

Industry insiders thought it might be healthier than smoking a joint because burning marijuana contains carcinogens like tar and carbon monoxide. “If we were really helping cancer patients, then adding carcinogens was not helpful,” said Kiloh, who in 2003 opened his first medical dispensary, Green Cross, in San Francisco, seven years after California legalized marijuana for medical purposes.

Federal Restrictions

Federal research restrictions allow the study of marijuana under certain conditions, and scientists at the University of California, San Francisco, found that the Volcano produced less carbon monoxide and tar compared with smoking marijuana.

The Volcano was built around inhalation of pure marijuana vapor, created by heating the plant itself. In a few years, the technology would change in a fundamental way.

“What happened was that the oil came next,” Kiloh said.

Entrepreneurs began to extract oil by bathing the leaf in ethanol or butane, filtering out the solid material that remained and then evaporating the solvent to leave the concentrated oil. Another method used carbon dioxide, which, when pressurized, creates a fluid that can be used to extract the oil. (There is no “toxicological” research about the relative health effects of the different methods, according to Christopher Havel, an analytical chemist at UCSF who works with Benowitz).

Once extracted, the THC oil could then be heated up using a small battery, kept in a cartridge or penlike case, creating aerosol, which is then inhaled from one end of the device. Consumers fell in love.

As marijuana became legal in a growing number of states, a new area of entrepreneurship burgeoned. Businesspeople found they could use the entire plant to extract oil rather than throw away stems and other parts discarded by smokers, which maximized the value of the crop.

The oil also could be mixed with other additives to give flavor, to create the effect of big puffs of smoke or just to cut the THC to substitute less expensive chemicals.

At the time, Kiloh was dubious: What was in these things? The packages either did not list ingredients or, if they did, the labels seemed untrustworthy, he said, because the oil sometimes smelled off.

Sometimes he would test the product and discover the THC had been watered down, initially with propylene glycol, which is used in fog machines, to add a smokey luster.

“People started getting greedy,” Kiloh said, describing the early vape pen manufacturers around 2012. “You didn’t know how much was propylene glycol and how much was THC.”

After initially carrying the vape pens in his dispensary, Kiloh temporarily pulled them from his shelves.

“I didn’t want to sell them,” Kiloh said. “What people said for the next three or four months was, ‘Can you bring them back?’” But he told them he wasn’t sure the pens were safe.

Downs, of Leafly, said the worry was valid. “It’s very clear innovation has eclipsed the sophistication of consumers as well as regulators and investigators,” he said. “We’ve been engaging in an uncontrolled mass experiment with inhaling concentrations of cannabinoids.”

In states that legalized marijuana, farmers could grow the crop openly, creating a vast, lower-cost supply that flooded not just legal markets but spilled into illegal ones, said Beau Kilmer, director of the Rand Drug Policy Research Center.

Prices plummeted. While national figures are hard to come by, Rand’s research shows that an oversupply in Oregon caused the price per pound to fall more than 50%, from $1,250 in 2016 to $500 in 2018.

“The fastest growing segment of the market is extract for inhalation,” Kilmer said.

And researchers remain in the dark. In August, the Drug Enforcement Administration loosened rules to allow some scientific institutions to apply to grow their own marijuana for study. However, the restrictions still prevent researchers like Benowitz from examining the kind of THC oil sold widely on the legal and black markets.

He summed up what little is known about vaping THC oil: “All we know is that there weren’t many problems until recently.”

This article originally appeared in

SAN FRANCISCO — For years, a divisive debate has raged in the United States over the health consequences of nicotine e-cigarettes. During the same time, vaping of a more contentious substance has been swiftly growing, with scant notice from public health officials.

Cannabis Oil and Vaping: Hazy Hazards

During a news briefing, Dr. Anne Schuchat, principal deputy director of the CDC, said officials expect more deaths because some people are suffering from severe lung illnesses.

But U.S. public health officials said they still were unable to pinpoint the cause, or causes, of the sicknesses that have resulted in hundreds of hospitalizations, with many in intensive care units.

Schuchat said some patients are on ventilators and therefore are unable to tell investigators what substances they vaped. “I wish we had more answers,” she said.

The CDC provided the first demographic snapshot of the afflicted: Nearly three-quarters are male, two-thirds between 18 and 34, and 16% are 18 or younger. “More than half of cases are under 25 years of age,” Schuchat said.

Illnesses have now been reported in 38 states and one U.S. territory.

In the most recent case, in St. Louis, officials said Thursday that a man in his mid-40s who had chronic pain had begun vaping last May. He was hospitalized Aug. 22 with respiratory problems and died Wednesday.

“He started out with shortness of breath and it rapidly progressed and deteriorated, developing into what is called acute respiratory distress syndrome,” or ARDS, said Dr. Michael Plisco, a critical care pulmonologist at Mercy Hospital St. Louis. “Once the lungs are injured by vaping, we don’t know how quickly it worsens and if it depends on other risk factors.”

He and other officials said they did not know what substance the patient had been vaping, but Plisco said that tissue samples from the lungs showed cells stained with oil.

Some products include oils that if inhaled — even small droplets — can cling to the lungs and airways and cause acute inflammation, doctors have said.

The first case in Canada also emerged this week. Officials there released information about a teenager in Ontario who was put on life support in an intensive care unit, but has now recovered.

The spate of illnesses this summer, coupled with the rising popularity of teenage vaping, has led a few states and the Trump administration to propose outlawing flavored e-cigarettes. Public officials hope restricting flavors that hold particular appeal for youth may discourage teenage use and adoption of vaping. Early results of an annual survey released Wednesday show that teenage vaping has doubled since 2017.

Vaping typically entails inhalation of aerosolized substances, usually nicotine or THC — the psychoactive ingredient in marijuana — mixed with solvents or other chemicals.

The CDC reiterated that many of the people who have gotten sick have used THC-based products, some obtained on the street, rather than from retailers in states where recreational or medical marijuana is legal. But CDC officials continued to emphasize they have not identified a single clear chemical or cause of the outbreak The officials said patients have report using THC, THC and nicotine and for some, just nicotine.

The CDC has said that to be safe for the time being, people should not vape anything at all.

The lack of answers has begun to elicit frustration from various camps, including consumers, policy experts and industry groups. Since mid-August, when public health officials first disclosed that nearly three dozen people had gotten sick, a clear cause has not been identified.

The agencies have pointed to the complexity of testing products and challenges of getting detailed history from patients about their behavior.

At the same time, a growing number of critics have said, there should be clearer results from the massive machinery of the federal investigation — more than 80 people at the CDC working on the issue, and a Food and Drug Administration lab in Cincinnati working with more than 150 samples from patients who got sick.

“We are not getting specific information we need to protect the public,” Dr. Michael Siegel, a pediatrician at Boston University who has been a strong advocate for the use e-cigarettes as a less dangerous alternative to traditional smoking. He said that the government has heavily implied that the problem is largely resulting from the use of illicit THC-related vaping products made but has not exonerated e-cigarettes, creating confusion.

“They’re not releasing the number of cases involved with THC,” he said. “That’s information they should be releasing.”

Eric Lindblom, an expert in tobacco policy at Georgetown Law School and a former FDA senior adviser, said that the FDA has the authority to ban the sale of THC vaping liquid, or THC vape pens, even in states where recreational marijuana is legal — or to ban sales that include any solvents other than ones known to be safe.

“They need to do something,” he said. “They should just take action to stop these things. It’s a no-lose situation.”

Mitchell Zeller, director of the FDA’s Center for Tobacco Products it would be premature to take further action until “we get answers to these questions.”

“We are in desperate need of facts and evidence,” he said during a news briefing with the CDC on Thursday. He said that there were multiple compounds showing up in the vaping mixtures, including vitamin E acetate and other additives. He said that vitamin E acetate did not appear to be the sole factor but did not elaborate on other substances involved.

Zeller also said that the FDA’s office of criminal investigations has begun “parallel investigative efforts.” He declined to specify any target of those efforts or whether an enforcement action is forthcoming, but he did say that particular arm of the FDA has gotten involved because it “has special investigative skills.”

Schuchat from the CDC said she understood the desire for more precise information. “We absolutely want to do that,” she said but added that in providing partial information, officials might “prematurely reassure” consumers about the safety of a product that ultimately turns out to be problematic.

One outstanding question, for instance, is whether there might be any connection between the recent bust in Wisconsin of an alleged vaping ring and the outbreak of illnesses. The bust involved seizing 57 canning jars filled with liquid thought to be THC, or contain it, and thousands of empty vaping cartridges.

The bust and the outbreak come against a backdrop of tremendous uncertainty, even confusion, at the federal level over the governance of both e-cigarettes and marijuana.

With e-cigarettes, the FDA has for years been developing regulations and policy about what products to allow into the market and under what circumstances. Recently, a federal court ruled that the FDA must demand that e-cigarette makers provide evidence by May of next year about their public health benefits or be pulled from the market.

The issue is even trickier with marijuana, which the federal government still considers to be a Schedule 1 drug, a category it shares with such deadly substances as fentanyl and heroin. Yet with nearly a dozen states having legalized recreational marijuana, and nearly three dozen allowing medicinal use, the federal government has essentially stood on the sidelines, trying to balance the growing political momentum behind legalization — as well as a burgeoning industry of cannabis and hemp products — against the uncertain health effects and longstanding federal policy.

Vaping Illnesses Increase to 530 Probable Cases, CDC Says

The number of vaping-related lung illnesses has risen to 530 probable cases according to an update Thursday by the Centers for Disease Control and Prevention, and a Missouri man became the eighth to die from the mysterious ailments.

In the most recent case, in St. Louis, officials said Thursday that a man in his mid-40s who had chronic pain had begun vaping in May. He was hospitalized Aug. 22 with respiratory problems and died Wednesday.

Zeller also said that the FDA’s office of criminal investigations has begun “parallel investigative efforts.” He declined to specify any target of those efforts or whether an enforcement action is forthcoming.

The issue is even trickier with marijuana, which the federal government still considers to be a Schedule 1 drug, a category it shares with such deadly substances as fentanyl and heroin. Yet with nearly a dozen states having legalized recreational marijuana, and nearly three dozen allowing medicinal use, the federal government has essentially stood on the sidelines, trying to balance the growing political momentum behind legalization — as well as a burgeoning industry of cannabis and hemp products — against the uncertain health effects and long-standing federal policy.

Eighth Death in Illness Tied to E-Cigarettes

Dr. Anne Schuchat, principal deputy director of the CDC, said officials expect more deaths because some people are suffering from severe lung illnesses.

During a briefing with reporters, the CDC provided the first demographic snapshot of the afflicted: Nearly three-quarters are male, two-thirds between 18 and 34, and 16% are 18 or younger. “More than half of cases are under 25 years of age,” Schuchat said.

At the same time, a growing number of critics have said, there should be clearer results from the massive machinery of the federal investigation — more than 80 people at the CDC working on the issue and a Food and Drug Administration lab in Cincinnati working with more than 150 samples from patients who got sick.

Vaping Illnesses Increase to 530 Probable Cases

The number of vaping-related lung illnesses has risen to 530 probable cases, and seven deaths are associated with the sickness, according to an update on Thursday by the Centers for Disease Control and Prevention.

But his best decisions, he said, relied on a tool as ancient as it is powerful. Piatt often began daily operations by breathing deliberately, slack-jawed, staring steadily at a palm tree.

Mindfulness — the practice of using breathing techniques, similar to those in meditation, to gain focus and reduce distraction — is inching into the military in the United States and those of a handful of other nations.

This winter, Army infantry soldiers at Schofield Barracks in Hawaii began using mindfulness to improve shooting skills — for instance, focusing on when to pull the trigger amid chaos to avoid unnecessary civilian harm.

The British Royal Navy has given mindfulness training to officers, and military leaders are rolling it out in the army and Royal Air Force for some officers and enlisted soldiers. The New Zealand Defence Force recently adopted the technique, and military forces of the Netherlands are considering the idea, too.

This week, NATO plans to hold a two-day symposium in Berlin to discuss the evidence behind the use of mindfulness in the military.

A small but growing group of military officials support the techniques to heal trauma-stressed veterans, make command decisions and help soldiers in chaotic battles.

“I was asked recently if my soldiers call me General Moonbeam,” said Piatt, who was director of operations for the Army and now commands its 10th Mountain Division. “There’s a stereotype this makes you soft. No, it brings you on point.”

The approach, he said, is based on the work of Amishi Jha, an associate professor of psychology at the University of Miami. She is the senior author of a paper published in December about the training’s effectiveness among members of a special operations unit.

The paper, in the journal Progress in Brain Research, reported that the troops who went through a monthlong training regimen that included daily practice in mindful breathing and focus techniques were better able to discern key information under chaotic circumstances and experienced increases in working memory function. The soldiers also reported making fewer cognitive errors than service members who did not use mindfulness.

The findings, which build on previous research showing improvements among soldiers and professional football players trained in mindfulness, are significant in part because members of the special forces are already selected for their ability to focus. The fact that even they saw improvement speaks to the power of the training, Jha said.

“They’re the best, and what they’re trying to do is the hardest,” she said.

Jha has spoken to the U.S. Army War College and the British Parliament, and she has been a consultant to New Zealand’s Defence Force and military officials in the Netherlands. “When the special forces do something,” she said, “not only does the rest of the U.S. military pay attention, but the rest of the world’s militaries pay attention.”

The science shows that techniques that focus and calm the mind allow people to perform better and make them less likely to overreact to incoming stimulation — whether a flash of movement, sound or an onslaught of information on a device.

The neuroscience of mindfulness involves, in part, strengthening a part of mental capacity known as “working memory” — a short-term, moment-to-moment catalog of tasks understood by scientists to effectively hold only a few pieces of information at one time.

As working memory clouds through overload, decisions become jumbled and reactions more impulsive. Breathing-induced focus lets people home in on the task at hand. But it does take practice.

The recent study found that service members who train for four weeks experience significant improvement, but those who train for only two weeks do not.

The mindfulness training comes as the military is exploring other options to intensify soldier focus, even the possibility of implanting computer chips into soldiers’ brains. But those potential solutions are expensive and years off.

Widespread adoption of mindfulness has challenges, including creating a staff of trainers, said Cmdr. William MacNulty, a commissioned officer in the U.S. Public Health Service. He helped train a special forces unit in mindfulness (the precise military branch and location are confidential). The program entailed the soldiers spending about 15 minutes each day performing recorded, guided breathing exercises.

MacNulty said that about a third of the soldiers readily embraced the idea, a third engaged with curiosity, and a third seemed skeptical.

MacNulty likened the benefits of practicing mindfulness to those of, say, doing push-ups. “You might not drop and do push-ups when you’re in a gunfight, but you have increased capacity,” he said. That’s true of mindfulness, he added: Mental focus “becomes a transferable skill.”

In the newsmagazine of the Royal New Zealand Air Force, known as the All Blacks, the military explained the rationale behind adopting mindfulness. Referring to its value, the magazine said: “The All Blacks talk about ‘red head/blue head’ — red head means being in a flustered state and blue head means being calm, centered and able to make clearheaded decisions.”

Research also has shown that use of mindfulness can help soldiers overcome post-traumatic stress disorder.

That has been the experience of Britain’s chief evangelist for use of mindfulness in the military, Cmdr. Tim Boughton.

Boughton, decorated for service in many combat zones, discovered when he retired from active duty in 2008 that he’d grown withdrawn and angered by the horrors he’d seen: mangled civilian bodies fused together in combat zones; deaths of 48 compatriots in battle in Iraq, Afghanistan, the Falklands, Northern Ireland; “ethnic cleansing, hand-to-hand stuff.”

When he went to a psychiatrist in 2008, she broke down in tears after he described his experiences. Boughton discovered mindfulness after his own bout with PTSD, eventually becoming a trustee of the Oxford University Mindfulness Center.

He now starts and ends his day with five minutes of breathing exercises. He uses the technique each time he is gripped by anxiety or panic. The traumas haven’t disappeared, he said, but he isn’t haunted by them daily. Now he can more calmly examine each terrible incident, address it and have some control over it — rather than merely reacting.

“The amount of brain power it frees by not being trapped in the past or the future is incredible,” Boughton said. “The military is seeing the mass benefits of this.”

Boughton has thought about whether mindfulness is anathema to conflict. “The purists would say that mindfulness was never developed for war purpose,” he said.

What he means is that mindfulness is often associated with peacefulness. But, he added, the idea is to be as faithful to compassionate and humane ideals as possible given the realities of the job.

Piatt underscored that point, describing one delicate diplomatic mission in Iraq that involved meeting with a local tribal leader. Before the session, he said, he meditated in front of a palm tree, and found himself extremely focused when the delicate conversation took place shortly thereafter.

“I was not taking notes. I remember every word she was saying. I wasn’t forming a response, just listening,” he said. When the tribal leader finished, he said, “I talked back to her about every single point, had to concede on some. I remember the expression on her face: This is someone we can work with.”

In the end, he said, mindfulness allowed him to “reduce conflict by better understanding.”

“I’m not saying, be soft,” he added. “I’m saying, understand how compassion and empathy can be used for real advantages.”

“Peace takes a lot of hard work.”

This article originally appeared in <a href="https://www.nytimes.com/2019/04/05/health/military-mindfulness-training.html" id="4b007549-50a7-3038-a414-a4b6354ddd3b">The New York Times</a>.

The Latest in Military Strategy: Mindfulness

As commander of the coalition forces in Iraq, Maj. Gen. Walter Piatt juggled ruthless pursuit of enemies and delicate diplomacy with tribal leaders, using a trove of modern weaponry and streams of tech-generated data.

The study, published Thursday in the journal Cell, focuses on colorectal and prostate cancer. These are among the cancers that seem largely impervious to a key mechanism of immunotherapy drugs.

The drugs block a signal that tumors send to stymie the immune system. That signal gets sent via a particular molecule that is found on the surface of some tumor cells.

The trouble is that the molecule, called PD-L1, does not appear on the surface of all tumors, and in those cases, the drugs have trouble interfering with the signal sent by the cancer.

The new study is part of a growing body of research that suggests that even when tumors don’t have this PD-L1 molecule on their surfaces, they are still using the molecule to trick the immune system.

Instead of appearing on the surface, the molecule is released by the tumor into the body, where it travels to immune system hubs, the lymph nodes, and tricks the cells that congregate there.

“They inhibit the activation of immune cells remotely,” said Dr. Robert Blelloch, associate chairman of the department of urology at the University of California, San Francisco, and a senior author of the new paper.

The UCSF scientists discovered that they could cure a mouse of prostate cancer if they removed the PD-L1 that was leaving the tumor and traveling to the lymph nodes to trick the immune system. When that happened, the immune system attacked the cancer effectively.

Furthermore, the immune system of the same mouse seemed able to attack a tumor later even when the drifting PD-L1 was reintroduced. This suggested to Blelloch that it might be possible to train the immune system to recognize a tumor much the way a vaccine can train an immune system to recognize a virus.

The work was done not in humans but in laboratory experiments and in mice, and it is not clear whether the results will translate in people. Dr. Ira Mellman, vice president of cancer immunology at Genentech, called the findings “a most interesting result.”

“But as with all mouse experiments, you get insight into basic mechanisms, but how it translates to the human therapeutic setting is unclear,” Mellman said.

He is skeptical, he said, but plans to meet shortly with Blelloch to discuss the implications of the work.

The new research dovetails with other recent studies, including a paper published last year in the journal Nature that showed that PD-L1 molecules released from skin cancer tumors can suppress the body’s immune function.

When these bits of PD-L1 travel outside the cell, they are known as exosomal, and the discovery of their role is one of many fast-moving developments refining an area of medicine that has become among the most promising in decades.

Late last year, the Nobel Prize was awarded to two scientists — James P. Allison of the M.D. Anderson Cancer Center in Houston, and Tasuku Honjo of Kyoto University in Japan — who did groundbreaking work in immunotherapy.

An explosion of additional research is aimed not only at refining the therapies — which can have profound side effects — but also at searching for other molecules involved in the perilous dance between cancer and the immune system.

Far more study is needed. But Blelloch said that the findings have him looking for ways to take the next steps into turning the discovery into a concrete therapy.

Interfering with the PD-L1 traveling to lymph nodes “can lead to a long-lasting, systemic, anti-tumor immunity,” the paper concluded.

This article originally appeared in <a href="https://www.nytimes.com/2019/04/04/health/cancer-immunotherapy-effectiveness.html" id="a51707cd-13e5-3173-adba-67757289cf6a">The New York Times</a>.

Cancer's Trick for Dodging the Immune System

Cancer immunotherapy drugs, which spur the body’s own immune system to attack tumors, hold great promise but still fail many patients. New research may help explain why some cancers elude the new class of therapies, and offer some clues to a solution.

— What is a drug-resistant urinary tract infection?

In the case of a resistant UTI, one or more standard antibiotics no longer work to cure the infection, but the bacteria is generally not resistant to all drugs.

— What can I do to avoid getting a UTI in the first place?

Women are more susceptible to UTIs, owing to the way these germs infect: They often travel through fecal residue from the rectum to the urethra; this can happen through sex or poor bathroom hygiene. Even taking great care does not make them entirely avoidable.

Here are some steps that can help prevent urinary tract infections: Drink plenty of fluids, which helps flush out the bladder. Empty your bladder after sexual intercourse. Practice good bathroom hygiene, which, simply put, means wiping from front to back.

During the reproductive years, women are as much as 50 times more likely than men to get a UTI. However, those numbers even out significantly in an aging population because men wind up getting surgical procedures, or have bowel control issues, that might lead to the same spread of germs from gut and rectum to the urinary tract.

— How often are UTIs resistant?

The majority of urinary tract infections are now resistant to one or more antibiotics. The drug ampicillin, once a common treatment, has been largely abandoned because most UTIs are now resistant to it.

The most important question isn’t whether an infection is resistant to any drug, but whether it is resistant to the drugs that are commonly used to treat your particular infection.

When experts in the field think about resistant UTIs, they say that resistance “depends on the bug and the drug.” What that means is that they try to figure out which particular germs are resistant to specific medications.

— What drugs work?

The drugs that are used to treat urinary tract infections have changed over the years, in large part because of rising resistance. Currently, there are a few “front-line” drugs that are recommended by various expert organizations, such as the Infectious Disease Society of America.

Two drugs that are the most highly recommended for uncomplicated UTIs are nitrofurantoin, sold as Macrobid, and trimethoprim-sulfamethoxazole, sold as Bactrim or Septra. Both require a prescription, with doses and time courses that vary with the medication. But there has been growing resistance to Bactrim.

Nitrofurantoin seems to be more effective. Urinary tract infections caused by E. coli were susceptible to it 96% of the time, the New York City health department found. But the nitrofurantoin tends not to work in more advanced UTIs where the infection reaches the kidneys, a condition known as pyelonephritis.

An older drug called fosfomycin has been revived as an alternative, but it is considered less effective than either nitrofurantoin or Bactrim. Other second-tier treatments tend to have either side effects or higher resistance rates.

— What about other remedies, like cranberry juice?

Science doesn’t back up the healing power of such remedies. However, they might appear to work because many UTIs will clear up over a few days as the body fights them off. In other cases, the symptoms may, in fact, be caused by another ailment that goes away on its own.

— How do I know if my particular strain of UTI is resistant to a particular drug?

The only way is to get a urine culture. The lab results will identify the germ and what would be effective in treating the infection. But it can take several days to get the results.

Most patients want an immediate prescription so doctors usually make a best-guess determination of what drug will work given a patient’s symptoms and history.

The importance of “history” cannot be overstated; if you have had a previous UTI, a previous resistant UTI, or have traveled outside the country, your history can help a doctor decide which drug to use.

Increasingly, experts tell us that you should ask for a culture when you go in for a UTI treatment, even if you get an immediate prescription. The culture will allow a doctor to change the drug if the first one does not work.

That said, there is an important catch about when to do a urine culture. Often, it will show bacteria in the bladder even when an infection is not present. Some amount of bacteria is normal. The Infectious Diseases Society of America cautions doctors against doing cultures when symptoms of a UTI are not present. The culture likely presence of bacteria can then lead to prescription of unnecessary antibiotics, contributing to the rise of resistance through overuse of the drugs.

Finally, some UTIs, even when there are symptoms, can clear up on their own. This is one of many reasons to seek the care of an informed professional.

What you need to know about resistant urinary tract infections

Urinary tract infections, or UTIs, are one of the world’s most common infections. Increasingly, they also are resistant to major drug treatments. Here’s what you should know.

The physician said the fungus was called Candida auris, and it appeared to have entered her bloodstream through a catheter or other intravenous line during her treatment. Spoor sent a text to the couple’s four children.

“Hey guys, I’m very sorry to do this via text but you need to know and not fair to wait until all of us are together,” he wrote. “The fungus mom has is the worst possible and can be terminal.”

He added: “It is a day to day issue so I don’t have any more answers or info at this time.”

Gregory Spoor, 67, an executive at a plumbing equipment company, wasn’t the only one with few answers. C. auris, a germ that typically is resistant to major anti-fungal medications, has been quietly confounding doctors, hospitals and infectious disease scientists around the world.

First identified in the ear of a woman in Japan in 2009 (“auris” is Latin for “ear”), the germ has spread around the globe, mostly appearing in hospitals and nursing homes, where it afflicts people with weakened immune systems.

Nearly 600 cases of C. auris have been reported in the United States, the majority of them in New York, New Jersey and Illinois. According to the Centers for Disease Control and Prevention, nearly half of people who contract the illness die within 90 days. But the true death rate is difficult to quantify because most patients have other medical conditions and their deaths may be attributed to other causes.

About 90 percent of C. auris strains are resistant to at least one drug, and 30 percent are resistant to two or more of the three major classes of anti-fungal drugs. However, Tuesday, the CDC confirmed that it has learned in the last month of the first known cases in the United States of so-called “pan-resistant” C. auris — a strain resistant to all major antifungals, said Dr. Tom Chiller, head of the agency’s fungal division, in an interview.

Such cases have been seen in several countries, including India and South Africa, but the two new cases, from New York state, have not been reported previously. Chiller said that it appeared that, in each case, the germ evolved during treatment and became pan-resistant, confirming a fear that the infection will continue to develop more effective defenses.

“It’s happening, and it’s going to happen,” Chiller said. “That’s why we need to remain vigilant and rapidly identify and control these infections.”

It often has been hard to gather details about the path of C. auris because hospitals and nursing homes have been unwilling to publicly disclose outbreaks or discuss cases, creating a culture of secrecy around the infection. States have kept confidential the locations of hospitals where outbreaks have occurred, citing patient confidentiality and a risk of unnecessarily scaring the public.

Stephanie Spoor’s family contacted The New York Times to share details of her case after reading an article in the newspaper about the emergence of C. auris and the growing threat of drug-resistant infections. Her experience sheds some light on the experience of dealing with the new health threat.

Northwestern Memorial has not issued any public announcement that it had cases of C. auris. The Illinois Department of Public Health confirmed Spoor’s case after the family gave officials permission to discuss it with The Times. But it would not disclose the identities of what it called “numerous” hospitals and nursing homes that have reported a total of 158 cases in the state since 2016.

Northwestern Memorial declined to answer any questions from The Times about Stephanie Spoor’s case, despite receiving permission from the Spoor family to cooperate.

The hospital also declined to respond to questions about how many C. auris cases it has treated, whether there were any current cases, what precautions it was taking and other queries.

“After careful consideration, we are going to pass on participating in this story,” Christopher King, a hospital spokesman, wrote in an email in response to questions.

Generally, health care institutions have said that they do not want to worry the public unnecessarily, given that they are working hard to control the spread of the infection and also that the germ is not a health threat to the general public. The people at the greatest risk are those who have compromised immune systems, typically through illness and age, and who are in hospitals and nursing homes where many infections are carried and transmitted.

Stephanie Spoor’s tale reveals the powerlessness of patients and institutions in the face of resistant infections.

Late last year, Spoor began experiencing shortness of breath and appeared to be having a surge of symptoms from lupus, an autoimmune disorder she had been diagnosed with years earlier but which did not seem to disrupt her daily life. Now, her lungs were having trouble absorbing oxygen.

Spoor’s family kept a detailed diary of the events, at her request. She went to Northwestern Memorial Hospital, a highly ranked academic medical center affiliated with Northwestern University. There, in mid-December, she had a biopsy that led to complications: The wound bled, and she went into cardiac arrest. She was revived and put on a device called an extracorporeal membrane oxygenation machine to help her breathe.

That machine was considered a way station to help Spoor survive until she could receive a lung transplant. She felt hopeful she would be able to see her youngest son, Zack, get married in a ceremony planned for June.

But a month later, a blood test found C. auris. Stephanie Spoor’s medical records, which the family shared with The Times, contained a note in mid-January in bold type: “This is a highly transmissible fungus that has a propensity to develop resistance.” The records continued, again in bold type, that it was necessary to “discuss with nurses to maintain diligent contact precautions and limited visitors if possible.”

Those records indicated that the hospital suspected Spoor picked up the infection from one of the tubes inserted into her body.

Spoor’s son Nicholas, 40, a Chicago architect, said that the day his mother was diagnosed with C. auris, he noticed the nurses and doctors in full protective aprons and gloves, using bleach to wipe off their feet when they entered and left the room. Everything in the room had a white glaze, he said, from the chemicals used to clean it.

“It was like a laboratory,” he said.

(Deadly Germs, Lost Cures): Gregory Spoor got the distressing news about his wife on the morning of Jan. 16 while standing outside her room in the intensive care unit at Northwestern Memorial Hospital in Chicago. The doctor explained that Stephanie Spoor, 64, had contracted a “rare, very rare, fungus.”