Apoorva Mandavilli

Fitness trackers such as Fitbit and Apple Watch already track step counts, heart rate and sleep rhythms. But they tend to be rigid and bulky, and mostly gather mechanical metrics, rather than assess a person’s underlying biology.

A new generation of devices instead aim to analyze sweat for many chemicals at once, producing a real-time snapshot of the wearer’s health or fitness. These devices also fit intimately against the skin, and are comfortable for anyone, from premature babies to the elderly. One version is already being advertised by Gatorade.

The latest advance in this technology, described Friday in the journal Science Advances, provides real-time information on the wearer’s pH, sweat rate, and levels of chloride, glucose and lactate — high levels of which could signal cystic fibrosis, diabetes or a lack of oxygen.

“It fits into a broader trend that you’re seeing in medicine, which is personalized, tailored approaches to treatment and delivery of care,” said John Rogers, a biomedical engineer at Northwestern University in Illinois and the key architect of the device.

Technology like this has been anticipated for years, but the field has accelerated rapidly. Some similar devices in development are soft. Some use electric sensors to read chemicals. Others rely on colorimetrics, in which the intensity of the color in the readout matches the concentration of the chemical being monitored. The new device delivers all of that in a battery-free and wireless form.

“This looks like the first version in which they integrated all of it in one device,” said Martin Kaltenbrunner, an engineering professor at Joannes Kepler University Linz, in Austria, who was not involved in the research. “The level of technology that is in this paper is very, very advanced.”

The new device has minuscule holes at its base into which sweat naturally flows. From there, a complex network of valves and microchannels, each roughly the width of a human hair, route the sweat into tiny reservoirs. Each reservoir contains a sensor that reacts with a chemical in the sweat, such as glucose or lactate.

“That’s basically it,” Rogers said. “There’s nothing that penetrates the skin, and there’s no power supply that’s driving flow.”

The device relies on the same technology that smartphones use to send wireless payments; the phone can both deliver power through this wireless coupling, and receives data back. Alternatively, the data could be sent to a reader attached to a treadmill or elsewhere in a fitness room — and, perhaps eventually, to a reader much farther away.

The system is versatile and could be set up to track the same chemical, or several, over time, such as the level of lactate in a runner as a marathon progresses. Because the device is waterproof and molded to the body, it also could be used by swimmers to track their performance.

Eventually, the device would fill up with sweat — not so hygienic — but the channel system can be easily separated from the electronics and swapped out, giving the device a longer life span. “This approach is especially nice, this modular construction of sensors,” Kaltenbrunner said.

To be marketed at large scale, any sweat-based sensor would need to be manufactured at a low cost. Many teams are focused on this goal because of the potential of the devices to transform health care, Kaltenbrunner said. “If I have to go to the clinic once a day to have my data collected, I wouldn’t really do it,” Kaltenbrunner said. “But it just means wearing a patch and being able to self-monitor myself, then eventually this barrier will be reduced.”

Rogers’ team has begun testing the technology as a way to screen for cystic fibrosis, a rare genetic condition. Doctors already look at chloride concentrations in sweat to identify children with the condition, but they typically use a rigid, uncomfortable device that straps tightly onto the child’s arm for a one-time measurement.

In 2017, another team described a flexible, wearable sensor that also analyzes chloride in sweat to screen for cystic fibrosis. But that sensor is battery-powered, and does not capture separate volumes of sweat as Rogers’ device does.

“Really what is needed is big data for human health,” said Ali Javey, a member of the team that proposed the earlier sensor and a professor of electrical engineering and computer science at the University of California, Berkeley. The device invented by Rogers “is really important,” Javey said, because it is “comfortable to wear, has different sensing modalities and is robust.”

Rogers’ team has been testing their device with children who have cystic fibrosis at Lurie Children’s Hospital of Chicago. It is in the late stages of a clinical trial, and plans to apply for approval from the Food and Drug Administration.

A much bigger market for sensors lies in helping the approximately 30 million people with diabetes in the United States track their glucose levels. The most advanced diabetes sensor, approved by the FDA in 2017, is a soft skin patch coupled to a small reader, and relies on tiny needles that pierce the skin to monitor blood glucose.

The ideal device would not involve needles or draw blood. To use sweat instead, however, scientists first need to learn more about it — how sweat rates vary among individuals, how different biochemicals make their way into sweat, and how well those levels reflect blood glucose.

“We need to take a step back and be careful to think about how we can make sense of what we’re measuring,” said Carlos Milla, Javey’s collaborator and a professor of pediatrics at Stanford University.

The new study underscores Milla’s concern. The device measured glucose in sweat, but the results suggested that this was not a good proxy for glucose in the blood. The sweat glucose levels reflect blood glucose from 30 to 60 minutes earlier, too long of a delay to help diabetics.

“It’s indicating this might not be as simple as one might have initially hoped,” Rogers said. He added that sweat glucose might be more helpful as a metric in screening for diabetes rather than for real-time monitoring of glucose levels.

Rogers is also working with collaborators to develop sensors for urea and creatinine, which are indicators of how well the kidneys are functioning, and to chart the progress of people undergoing rehabilitation after a stroke. Other labs, such as one led by Wei Gao at Caltech University, are trying to develop sensors for mental health conditions, including depression.

Progress on many of these fronts is likely to be fast. In November 2016, Rogers described an earlier vision of his device that used colorimetric analysis of sweat. Within weeks, he was in talks with Gatorade and L’Oreal to adapt the technology. In December, Gatorade debuted a commercial that featured Serena Williams and hinted at an upcoming range of products based on the nature of people’s sweat. And L’Oreal is promoting a small sticker that will track skin hydration. (Rogers’ device was also featured in an exhibition of the Museum of Modern Art in New York, and has since become part of the permanent collection.)

“It shows you how quickly this can happen,” Rogers said. “Two, three years is a very conservative estimate.”

This article originally appeared in <a href="https://www.nytimes.com/2019/01/18/health/wearable-tech-sweat.html" id="d554ac50-221c-3fcb-a100-5a4a014c26d4">The New York Times</a>.

Someday soon, perhaps within a year, you’ll be able to slap a soft, stretchy patch on to your arm that tells you if you’re dehydrated. Or that your electrolytes are dangerously out of balance. Or even that you have diabetes.

Your Sweat Will See You Now

<h1>In the earliest days after birth, millions of bacteria make their home in a baby’s body — in the skin, mouth and especially the gut. These immigrants come from the birth canal and the mother’s feces (during a vaginal birth), the mother’s skin and mouth as she holds and nuzzles the baby and perhaps even from the placenta, although that source is still debated.</h1>

The colonizing microbiome can have a far-reaching impact on the baby’s health. Studies have suggested, for instance, that the populace of a baby’s microbiome in the first two years of life may predict later risk of obesity. Children born by cesarean section are also more likely to become obese, or to develop autoimmune diseases such as type 1 diabetes and asthma.

Lately, scientists have identified another major contributor to the infant microbiome. breast milk, it turns out, is teeming with bacteria that colonize the infant’s gut, and could help set the course for the baby’s growing immune system and metabolism.

Moreover, breast milk seems to be rich in beneficial bacteria only when it comes directly from the mother’s breast — not even when the same milk is pumped and delivered later by bottle. Pumped milk still carries most other riches of breast milk. Nevertheless, this news about the microbiome, emerging from studies done in the past few years, taps into a fraught issue for many women: medical recommendations and societal pressure to breast-feed, combined with policies, or physical problems, that often make it all but impossible to do so.

Especially for the gut microbiome of older babies, “the number one thing that influences that composition is what they’re being fed,” said Meghan Azad, a pediatric researcher and epidemiologist at the University of Manitoba. “In some ways that message isn’t for individual moms, but for society overall: Breast-feeding is very important.”

The idea of a breast milk microbiome, and of its importance, is only just beginning to take root. The numbers of bacteria in breast milk are much lower than in stool, the usual route to sample gut bacteria, and scientists lacked the tools to analyze breast milk. As the technology has matured, researchers have found that breast-feeding seems to have an outsize impact, populating the baby’s microbiome with good bacteria.

It’s well known by now that babies born by cesarean section miss out on many helpful bacteria. And antibiotic use in the mother or baby can also obliterate the baby’s nascent bacterial populations. Breast-feeding can compensate to some extent.

“Those instructions come very early in life,” said Jed Friedman, director of the Harold Hamm Diabetes Center at the University of Oklahoma. “The problem becomes if you can’t breast-feed and are switching to formula, and maybe you’re getting antibiotics — if you wipe out all these sources then you’ll see big changes. When you add all those together it’s a triple whammy.”

A recent series of studies has cast light on a particularly beneficial type of microbe, called bifidobacteria. Groundbreaking work published in 2012 by Omry Koren, who runs the Microbiome Research Lab at Bar-Ilan University in Israel, showed that the microbiome evolves during pregnancy. Over time, it becomes similar to a state that resembles inflammation and metabolic syndrome — a condition associated with heart disease, stroke and Type 2 diabetes. In April, Koren’s team showed that, late in pregnancy, bifidobacteria sense a gestational hormone called progesterone and proliferate in response, as if preparing for the breast-feeding phase.

“We actually think there is a sort of evolutionary mechanism here, which basically causes bifidobacterium to grow faster,” Koren said. “The fact that bacteria can sense human hormones and react to those hormones, I think that’s pretty fascinating.”

Bifidobacteria consume special sugars found in breast milk, called human milk oligosaccharides, that babies cannot otherwise digest. As a result, these bacteria are abundant in the guts of breast-fed infants but not of formula-fed babies.

Breast milk has long been known to contain human milk oligosaccharides, but the discovery that they’re important for the microbiome to thrive has drawn attention to them. Cows make about 40 different oligosaccharides, and humans make more than 100, although each woman’s breast milk contains a subset of that number.

A woman’s breast milk also contains a unique mélange of hormones, antibodies and bacteria — a brew that presumably evolved to meet the needs of her child. “It’s one of the unique things about human milk that’s really hard to replicate,” Azad said. “A formula is an attempt at making something that’s one-size-fits-all, essentially.”

Formula manufacturers keep up with the science on breast milk, and they strive to mimic the substance as closely as possible. But in the case of oligosaccharides, they may have jumped the gun: Some companies are adding one of the complex sugars, called 2FL, to their products (and are testing many others). However, about 20% of women don’t produce 2FL in their breast milk. If one of these women gives her baby a formula that contains 2FL, the baby receives a sugar that it would not have received naturally, Azad said: “And is that a good thing? Is that a bad thing? We don’t really know yet.”

Adding just one sugar also may not provide much benefit. Research suggests that only about 10 of the sugars seem to be particularly important for a baby’s health — but only when consumed in combination.

“What is the function of those components if they’re isolated and not all in combination with each other?” said Dr. Andrew Bremer, a pediatric researcher at the Eunice Kennedy Shriver National Institute of Child Health and Human Development, in Bethesda, Maryland. “Just adding one to a predefined formula, is that comparable to breast milk? Or, heaven forbid, is it deleterious?”

Breast milk that is pumped and delivered by bottle is generally better than formula, Azad said. But she had some additional news that some working mothers may find unsettling: Pumped breast milk may not deliver the benefits of the sugars that arrive in breast milk straight from the source.

Azad and her colleagues studied 393 Canadian mother-infant pairs and found that pumped breast milk seems to be richer in some harmful bacteria, and has few bifidobacteria. Many variables can affect the quality of pumped breast milk, including the type of pump, how the milk is stored and the cleanliness of the bottles and nipples. Azad’s work suggests that direct contact between the mother’s breast and the baby’s mouth is important: When a baby nurses, some denizens of its oral microbiome may traverse back into the mother’s breast.

In other words, the benefits of breast-feeding may derive from myriad factors, including the many microbiomes in the mother’s body — in the breast milk and on the skin of the breast — and in the baby’s mouth and gut.

“I don’t want the message to be that expressed human milk is bad,” Bremer said. “It’s that there are other factors involved. When you disrupt that experience of baby sucking on the mom’s breast, what do you lose? Or what’s gained by that process? The science is more ripe now to start delving into those questions.”

Doctors should also exercise caution when prescribing antibiotics to babies or to lactating mothers, he said. There is robust evidence that antibiotics can have a powerful negative effect on the microbiome, shifting the balance toward harmful bacteria.

For some women and babies, forgoing antibiotics is not an option. As many as 1 in 4 pregnant women are infected with group B strep bacteria, and may need intravenous antibiotics during labor to lower the risk of infecting their babies. Those women are encouraged to minimize the effects on the microbiome by several means, including vaginal delivery, exclusively breast-feeding, providing abundant skin-on-skin contact with the baby, and avoiding giving the infant scented baths, which can disrupt its microbiome.

“Those things, then, really, overwhelmingly promote a beautiful growth of healthy bacteria both on the skin of the baby and in the gut,” said Sara Edwards, a researcher at Emory University’s Nell Hodgson Woodruff School of Nursing.

Edwards and her colleagues are following nearly 600 pregnant women to track relationships between their antibiotic use at different stages of gestation and the long-term effects on mother and baby. No definitive patterns have emerged yet, but the changes in the mothers seem to be short-lived.

“It looks as if the body does a pretty good job,” Edwards said. “Especially among people who are healthy and don’t have other comorbidities and other immune issues — that there is a correction that occurs once the antibiotics are over.”

Women also should exercise, avoid stress and eat foods that either contain or nourish good bacteria, including yogurt, kefir, kombucha and sauerkraut, she added.

“Things that promote wellness in the mother also produce the richest, healthiest type of diet for the babies’ milk,” Edwards said.

Here again, breast-feeding seems to be what’s most helpful. But women who have trouble breast-feeding shouldn’t despair, Azad said.

“One thing that’s pretty clear is that there’s a dose response, meaning that every bit counts,” she said. “So even if you can’t do six months of breast-feeding, if you can do partial breast-feeding, or if you can do one month, or one week, that’s definitely better than none.”

This article originally appeared in <a href="https://www.nytimes.com/2019/06/12/health/breastmilk-microbiome-parenting.html" target="_blank">The New York Times</a>.

The latest reason to breast-feed: Milk is alive

Lately, scientists have identified another major contributor to the infant microbiome. breast milk, it turns out, is teeming with bacteria that colonize the infant’s gut, and could help set the course for the baby’s growing immune system and metabolism.

Three years ago, Siddamma’s mother-in-law developed pale patches on her arms. But Siddamma, 32, did not get along with her, and did not pry. A year or so later, she noticed that her husband had similar marks on his back — but he was on a rare visit home from herding goats, so she was reluctant to raise the issue. She suggested that he see a doctor, and left it at that.

Then, one day in 2017, she returned home from work and saw her son Lingappa, then 9, crying. He told her he couldn’t go back to school because the other boys were making fun of the ulcers on his face. That did it, Siddamma said: “I have only one son.”

Eventually she brought him 50 miles from Mudumal, where the family lives, to Mahabubnagar, a town of 200,000 people in the southern Indian state of Telangana. A dermatologist in the town referred Siddamma to a specialized clinic, where a doctor determined that the boy had leprosy. “I didn’t know anything about it before then,” Siddamma said.

Leprosy is the result of infection with Mycobacterium leprae, a close cousin of the bacterium that causes tuberculosis. The disease has been around for centuries, but because it cannot be cultured in the lab, its mysteries remain unsolved.

Leprosy often starts off with the sort of discolored, numb patches that appeared on Siddamma’s family members, or with tiny nodules under the skin. Left untreated, the bacteria slowly destroy nerves and muscles, eventually leading to the deformities associated with the disease, and to permanent disability.

The disease has all but disappeared from most parts of the world, thanks in part to a yearlong multidrug treatment, donated by pharmaceutical company Novartis. In 2005, India declared that leprosy was no longer a problem in the country. But that announcement was premature: According to the World Health Organization, India harbors 60 percent of the world’s cases, with more than 100,000 new diagnoses each year.

As India’s health officials concede, the prevalence of leprosy was low in 2005 not because fewer residents were being infected, but because the government stopped trying to find them.

“Sometimes the program managers start making less effort, so they get less cases, so that they can say that prevalence is going down,” said Dr. Anil Kumar, who has led the country’s leprosy program since 2015.

There is no blood test for the disease, and scientists aren’t entirely sure how it is transmitted. Contact with infected people is one way, but not a certain one: Siddamma’s younger daughters also became infected, but an older daughter, and Siddamma herself, remained unaffected.

“Does genetics play a role? Maybe,” said Dr. Paul Fine, an epidemiologist at the London School of Hygiene and Tropical Medicine. “Does prior immune status play a role? Maybe.” Nutrition, access to health care and socioeconomic status all might be involved, he said: “We frankly don’t know.”

‘A Lot of Collateral Damage’

Clarity or no, the World Health Organization has long made the elimination of leprosy one its goals. In 1991, the organization announced that by 2005 leprosy would be “eliminated as a public health problem,” meaning that there would be fewer than one case per 10,000 people.

The odds were long — the deadline had been deferred once already — but “sometimes you put intentionally targets which are rather aspirational,” said Dr. Erwin Cooreman, team leader of the organization’s Global Leprosy Program.

But the subtleties of that aspiration were lost on most people in India.

“People actually just completely misunderstood it,” said Dr. Diana Lockwood, a leprosy expert at the London School. “For them, elimination means no cases.”

People infected with the leprosy bacterium may not show symptoms for 20 years. Meanwhile, they still can infect others, who in turn may remain symptom-free, and infectious, for years. Reducing the number of visible cases of leprosy is a start toward eliminating the disease, but it is hardly the end.

Still, health officials in India took the goal of elimination seriously, and by 2005 the number of symptomatic cases dropped to fewer than one case per 10,000 people. Then the country dismantled most of its leprosy programs and redirected its resources to more urgent priorities such as AIDS and tuberculosis; public awareness of leprosy plunged.

But out of view, the bacterium remained active. The number of infected, disabled people remained low for nearly a decade, and then began to rise. The disease was being detected way too late, generating “lot of collateral damage,” Cooreman said.

Leprosy causes distinct deformities and imposes a heavy social stigma.

Indian law forbids people with the disease from working and traveling in public. One returning patient at the Mahabubnagar clinic, a well-educated man in his late 20s, had not told anyone in his family, not even his mother, because he was terrified that the news might leak to his neighbors. People with the disease sometimes exile themselves to leprosy “colonies” — there are 700 or so in the country — where they interact only with one another and beg for money.

The stigma, in turn, makes the disease harder to detect and eliminate. “In countries like India, people from all classes get leprosy,” said Ashim Chowla, who heads a nonprofit agency called Lepra. “But because of discrimination and prejudice, we don’t talk about it. And because we don’t talk about it, we don’t know who’s got leprosy and who doesn’t.”

Fighting Myths and Misinformation

Organizations such as Lepra help people with the disease fight for government benefits. Pressured by the organization, India’s Supreme Court ruled in September that the government must end discriminatory laws, conduct regular surveillance to detect new cases, provide treatment to everyone who needs it, and promote awareness of leprosy as a curable disease. “We work to make leprosy a disease of no consequence, which is what it should be,” Chowla said.

The organization runs 26 local clinics in India, including the one in Mahabubnagar that Siddamma visited with her son. On one hot day in February, the staff tested three new cases and followed up with 17 previously diagnosed ones: men and women, children and older adults, rich and poor.

The awareness campaigns are key to combating the myths and misinformation that surround leprosy. Chowla recalled a tribal woman he had met in Chattisgarh, a locus of the disease in northern India. The woman’s fingers were clawed, a signature effect of leprosy. But she saw no point in visiting a doctor. The disease was an intergenerational curse, she said: Her grandmother once had boiled frogs in a fit of annoyance at their loud croaking, and the frogs had taken revenge on her, the granddaughter.

Chowla had leprosy as a child; he thought the hairless patch on his left arm was magical, and dared his friends to plunge sharp objects through his numb skin. He has been cured for decades, but doctors still shrink from him when they hear about his diagnosis.

“Just because my mum was clever enough to get me to a dermatologist, and the dermatologist was clever enough to diagnose me, I got cured,” he said.

Kumar, head of India’s leprosy program, has taken steps to raise awareness of the disease and combat the stigma around it. On World Leprosy Day — Jan. 30 — he encourages the leaders of the more than 600,000 villages in the country to talk about the disease.

Chowla recalled an awareness session that Lepra held in a remote village in September 2017. About one-quarter of the village’s 1,000 residents attended and were examined, and nine cases were diagnosed. When Kumar heard about the cases, he immediately launched a districtwide awareness campaign. By November 2018, the reported prevalence of leprosy in that district had more than doubled, a sign that health officials were becoming more successful at finding hidden cases.

The numbers of cases must first go up, as such cases are revealed, before they can go down, Kumar said. More important is that the number of visible deformities has fallen by 25 percent. “It means we are preventing disability,” he said. “We are detecting cases early. And it also means we have cut down transmission at the community level.”

He has embraced the WHO’s latest targets for leprosy, to be achieved by 2020: to decrease the number of new diagnoses in patients with visible deformities to fewer than one per million, and the number of children with disabilities to zero.

With luck, Siddamma’s children received treatment early enough to avoid disability. But it came at the cost of great effort. Few doctors in India are familiar with leprosy, and they are far between.

To reach the leprosy clinic, Siddamma and her children woke early, took a three-wheeler from their home to a bus stop several miles away, then took a long bus ride to the clinic. The cost of the ticket was not trivial. Siddamma was tired. At one point, she unconsciously lapsed into her native Kannada from her patchy Telugu, the language spoken at the clinic.

And she was worried about her youngest daughter who, despite three months of treatment, still has many patches on her arms. To make sure she is cured, Siddamma would need to make the long journey at least once more.

This article originally appeared in <a id="1eb38ad1-7b13-362f-a43a-e5474c1d740f" href="https://www.nytimes.com/2019/04/17/health/leprosy-india-disease.html">The New York Times</a>.

In India, a Renewed Fight Against Leprosy

(Science Times)

In India, a renewed fight against leprosy

<h1>At a scientific conference in Seattle on Tuesday, researchers reckoned with a day that many thought might never arrive. A patient appears to have been cured of HIV, the virus that causes AIDS, for only the second time since the epidemic began.</h1>

A sort of electric hope hangs in the air, said Dr. Steve Deeks, an AIDS specialist at the University of California, San Francisco, who is attending the gathering: “The whole approach to a cure is shifting more from aspiration to something that people are realizing could be feasible.”

It is a hope that must be tempered with realism: HIV is a wily adversary, and scientists and patients living with the virus are all too well acquainted with past failures in the fight against the epidemic.

Here’s what the news means right now.

Will this change anything for people living with HIV?

Not yet. The second case does provide “proof of concept,” shining a light on a potential path to an HIV cure. Scientists intend to pursue it with vigor.

But this apparent success does not mean that an easy cure is around the corner, and certainly not that infected patients should stop taking their pills.

“Sometimes the amount of desperation for a cure is driven by the stigma that’s still out there,” said Richard Jefferys, a director at Treatment Action Group, an advocacy organization. “But while two or three people is a drop in the ocean compared to the 35 million HIV-positive people in the world, it’s a whole lot better than zero.”

Both men believed to have been cured so far had HIV and cancer. Both received bone-marrow transplants to treat the cancer, not the HIV. In each case, the bone-marrow donors carried a key genetic mutation, called delta 32, that hampers HIV’s entry into certain blood cells.

Bone-marrow transplants are risky procedures, so this is not likely to be a treatment option for the majority of people with HIV. And it is worth noting that until now, most other attempts to repeat the first cure had also failed.

Whatever the path to a cure turns out to be, it will not be simple.

Remission? Cure? What’s the difference?

Cure means the virus seems to be gone forever. Remission is a more conservative term: The virus is under control in the body, but maybe not forever.

Before scientists described the case Monday, there had been only one widely accepted example of a cure: Timothy Ray Brown, 52, who has remained free of HIV for 12 years after two bone-marrow transplants.

After his case, there were many failed attempts to duplicate this success. Each time, the virus came back after the patient stopped taking anti-HIV drugs.

The newly reported case, in a man described only as the “London patient,” has been HIV-free for 18 months since stopping the drugs. Extraordinarily sensitive tests cannot find the virus in his body. To some scientists, that’s a cure. Others are more sanguine.

“We don’t have any international agreement on what time without viral rebound is necessary to speak about cure,” said Dr. Annemarie Wensing, a virologist at the University Medical Center Utrecht in the Netherlands.

It is worth noting that there have been patients who went into remission without a bone-marrow transplant. In these cases, the immune system seems able to maintain tight control over the virus, even without drugs. For years, researchers have been trying to figure out how it happens.

What’s the next step?

A transplant from a delta 32 donor essentially wipes out the immune cells that are vulnerable to HIV, replacing them with cells that are resistant to the virus. Already many groups of scientists are trying to mimic the benefits of a bone-marrow transplant without risks of the actual procedure.

The delta 32 mutation occurs in a gene that directs production of a protein called CCR5, which sits on the surface of certain immune cells. A common type of HIV needs this protein, among others, to enter cells in order to reproduce.

The gene that directs production of CCR5 may be modified with newer gene therapy techniques, similar to treatments developed for hemophilia and sickle-cell disease. And scientists have tried to edit CCR5 from a person’s immune cells in the lab and to infuse the modified cells back into the body.

But so far the numbers of cells derived with this method do not seem to be enough to make anyone resistant to HIV.

In one trial funded by Sangamo Therapeutics, however, researchers reported a curious finding: Although the infusion did not cure HIV infection, the amount of virus in the body seemed to decline by a thousandfold. The company is planning a follow-up study to explore this further.

Another approach would be to deliver enzymes that edit the genes directly into the body. The real challenge is in targeting the enzymes: Many teams are looking into delivery via nanoparticles, for example, but this strategy is years from success, Deeks said.

An even more intriguing option is to design a predecessor stem cell that would produce a steady stream of HIV-resistant immune cells in the body. At least one group in China is trying to edit CCR5 from stem cells that can be infused into patients with both cancer and HIV.

Early studies at the University of Pennsylvania suggest that something like this might work, noted Dr. Mike McCune, a global health adviser to the Bill and Melinda Gates Foundation.

In addition, some scientists are trying to force the virus into remission with broadly neutralizing antibodies, immune molecules that can disable various types of HIV.

How soon might a new treatment be available?

Five to 10 years at the earliest. And that covers only types of HIV that rely on CCR5 to infect cells. Another form of HIV, called X4, relies on a different protein to enter cells; none of these theoretical treatments would guard against infection with that form of the virus.

“Nobody should really be anticipating a cure or a remission is around the corner,” McCune said.

But gene therapy and gene editing are moving at a lightning pace, and it is not unreasonable to think that some researcher somewhere will find a way to do for the immune system what these bone-marrow transplants did for these two patients.

“We need to push on multiple fronts at once,” McCune said.

This article originally appeared in <a id="a2823367-0d00-4cbf-a8eb-a4e7e9d360bb" href="https://www.nytimes.com/2019/03/05/health/hiv-aids-cure.html">The New York Times</a>.

As word of a second HIV cure spreads, patients wonder: What now?

It is a hope that must be tempered with realism: HIV is a wily adversary, and scientists and patients living with the virus are all too well acquainted with past failures in the fight against the epidemic.

<h1>For just the second time since the global epidemic began, a patient appears to have been cured of infection with HIV, the virus that causes AIDS.</h1>

The news comes nearly 12 years to the day after the first patient known to be cured, a feat that researchers have long tried, and failed, to duplicate. The surprise success now confirms that a cure for HIV infection is possible, if difficult, researchers said.

The investigators are to publish their report Tuesday in the journal Nature and to present some of the details at the Conference on Retroviruses and Opportunistic Infections in Seattle.

Publicly, the scientists are describing the case as a long-term “remission.” In interviews, most experts are calling it a cure, with the caveat that it is hard to know how to define the word when there are only two known instances.

Both milestones resulted from bone-marrow transplants given to infected patients. But the transplants were intended to treat cancer in the patients, not HIV.

Bone-marrow transplantation is unlikely to be a realistic treatment option in the near future. Powerful drugs are now available to control HIV infection, while the transplants are risky, with harsh side effects that can last for years.

But rearming the body with immune cells similarly modified to resist HIV might well succeed as a practical treatment, experts said.

“This will inspire people that cure is not a dream,” said Dr. Annemarie Wensing, a virologist at the University Medical Center Utrecht in the Netherlands. “It’s reachable.”

Wensing is co-leader of IciStem, a consortium of European scientists studying stem cell transplants to treat HIV infection. The consortium is supported by AMFAR, the American AIDS research organization.

The new patient has chosen to remain anonymous, and the scientists referred to him only as the “London patient.”

“I feel a sense of responsibility to help the doctors understand how it happened so they can develop the science,” he told The New York Times in an email.

Learning that he could be cured of both cancer and HIV infection was “surreal” and “overwhelming,” he added. “I never thought that there would be a cure during my lifetime.”

At the same conference in 2007, a German doctor described the first such cure in the “Berlin patient,” later identified as Timothy Ray Brown, 52, who now lives in Palm Springs, California.

That news, displayed on a poster at the back of a conference room, initially gained little attention. Once it became clear that Brown was cured, scientists set out to duplicate his result with other cancer patients infected with HIV.

In case after case, the virus came roaring back, often around nine months after the patients stopped taking antiretroviral drugs, or else the patients died of cancer. The failures left scientists wondering whether Brown’s cure would remain a fluke.

Brown had leukemia, and after chemotherapy failed to stop it, needed two bone-marrow transplants.

The transplants were from a donor with a mutation in a protein called CCR5, which rests on the surface of certain immune cells. HIV uses the protein to enter those cells but cannot latch on to the mutated version.

Brown was given harsh immunosuppressive drugs of a kind that are no longer used, and suffered intense complications for months after the transplant. He was placed in an induced coma at one point and nearly died.

“He was really beaten up by the whole procedure,” said Dr. Steven Deeks, an AIDS expert at the University of California, San Francisco, who has treated Brown. “And so we’ve always wondered whether all that conditioning, a massive amount of destruction to his immune system, explained why Timothy was cured but no one else.”

The London patient has answered that question: A near-death experience is not required for the procedure to work.

He had Hodgkin lymphoma and received a bone-marrow transplant from a donor with the CCR5 mutation in May 2016. He, too, received immunosuppressive drugs, but the treatment was much less intense, in line with current standards for transplant patients.

He quit taking anti-HIV drugs in September 2017, making him the first patient since Brown known to remain virus-free for more than a year after stopping.

“I think this does change the game a little bit,” said Dr. Ravindra Gupta, a virologist at University College London who presented the findings at the Seattle meeting. “Everybody believed after the Berlin patient that you needed to nearly die basically to cure HIV, but now maybe you don’t.”

Although the London patient was not as ill as Brown had been after the transplant, the procedure worked about as well: The transplant destroyed the cancer without harmful side effects. The transplanted immune cells, now resistant to HIV, seem to have fully replaced his vulnerable cells.

Most people with the HIV-resistant mutation, called delta 32, are of Northern European descent. IciStem maintains a database of about 22,000 such donors.

So far, its scientists are tracking 38 HIV-infected people who have received bone-marrow transplants, including six from donors without the mutation.

The London patient is 36 on this list. Another one, number 19 on the list and referred to as the “Düsseldorf patient,” has been off anti-HIV drugs for four months. Details of that case will be presented at the Seattle conference later this week.

The consortium’s scientists have repeatedly analyzed the London patient’s blood for signs of the virus. They saw a weak indication of continued infection in one of 24 tests, but say this may be the result of contamination in the sample.

The most sensitive test did not find any circulating virus. Antibodies to HIV were still present in his blood, but their levels declined over time, in a trajectory similar to that seen in Brown.

None of this guarantees that the London patient is forever out of the woods, but the similarities to Brown’s recovery offer reason for optimism, Gupta said.

“In a way, the only person to compare with directly is the Berlin patient,” he said. “That’s kind of the only standard we have at the moment.”

Most experts who know the details agree that the new case seems like a legitimate cure, but some are uncertain of its relevance for AIDS treatment overall.

“I’m not sure what this tells us,” said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases. “It was done with Timothy Ray Brown, and now here’s another case — ok, so now what? Now where do we go with it?”

One possibility, said Deeks and others, is to develop gene-therapy approaches to knock out CCR5 on immune cells or their predecessor stem cells. Resistant to HIV infection, these modified cells should eventually clear the body of the virus.

(CCR5 is the protein that He Jiankui, a scientist in China, claimed to have modified with gene editing in at least two children, in an attempt to make them resistant to HIV — an experiment that set off international condemnation.)

Several companies are pursuing gene therapies but have not yet been successful. The modification must target the right number of cells, in the right place — only the bone marrow, for example, and not the brain — and tweak only the genes directing production of CCR5.

“There are a number of levels of precision that must be reached,” said Dr. Mike McCune, a senior adviser on global health to the Bill and Melinda Gates Foundation. “There are also concerns that you might do something untoward, and if so you might wish to have a kill switch.”

Several teams are working on all of these obstacles, McCune said. Eventually, they may be able to develop a viral delivery system that, when injected into the body, seeks out all CCR5 receptors and deletes them, or even a donor stem cell that is resistant to HIV but could be given to any patient.

“These are dreams, right? Things on the drawing table,” McCune said. “These dreams are motivated by cases like this — it helps us to imagine what might be done in the future.”

One important caveat to any such approach is that the patient would still be vulnerable to a form of HIV called X4, which employs a different protein, CXCR4, to enter cells.

“This is only going to work if someone has a virus that really only uses CCR5 for entry — and that’s actually probably about 50 percent of the people who are living with HIV, if not less,” said Dr. Timothy J. Henrich, an AIDS specialist at the University of California, San Francisco.

Even if a person harbors only a small number of X4 viruses, they may multiply in the absence of competition from their viral cousins. There is at least one reported case of an individual who got a transplant from a delta 32 donor but later rebounded with the X4 virus. (As a precaution against X4, Brown is taking a daily pill to prevent HIV infection.)

Brown says he is hopeful that the London patient’s cure proves as durable as his own. “If something has happened once in medical science, it can happen again,” Brown said. “I’ve been waiting for company for a long time.”

This article originally appeared in <a id="99adb1e0-c8d6-4ab9-ae82-6bcabc2886c5" href="https://www.nytimes.com/2019/03/04/health/aids-cure-london-patient.html">The New York Times</a>.

HIV Is Reported Cured in a Second Patient, a Milestone in the Global AIDS Epidemic

The investigators are to publish their report Tuesday in the journal Nature and to present some of the details at the Conference on Retroviruses and Opportunistic Infections in Seattle.

HIV is reported cured in a second patient, a milestone in the global AIDS epidemic

<h1>Someday soon, perhaps within a year, you’ll be able to slap a soft, stretchy patch on to your arm that tells you if you’re dehydrated. Or that your electrolytes are dangerously out of balance. Or even that you have diabetes.</h1>

The device relies on the same technology that smartphones use to send wireless payments; the phone can both deliver power through this wireless coupling, and receives data back. Alternatively, the data could be sent to a reader attached to a treadmill or elsewhere in a fitness room.

The system is versatile and could be set up to track the same chemical, or several chemicals, over time, such as the level of lactate in a runner as a marathon progresses. Because the device is waterproof and molded to the body, it also could be used by swimmers.

Progress on many of these fronts is likely to be fast. In November 2016, Rogers described an earlier vision of his device that used colorimetric analysis of sweat. Within weeks, he was in talks with Gatorade and L’Oreal to adapt the technology. In December, Gatorade debuted a commercial that featured Serena Williams and hinted at an upcoming range of products based on the nature of people’s sweat. And L’Oreal is promoting a small sticker that will track skin hydration.

This article originally appeared in <a id="0c5bfea0-26a0-4a69-b15a-2703abf3d929" href="https://www.nytimes.com/2019/01/18/health/wearable-tech-sweat.html">The New York Times</a>.

A Patch Uses Sweat to Get a Read on Your Body's Toil