TIME medicine

This New Kind of Stem Cell May Revolutionize How We Treat Diseases

Scientists have created a new type of stem cell that could speed treatments for diseases and make them safer

Ever since Japanese researcher Shinya Yamanaka found a way to treat skin cells with four genes and reprogram them back to their embryonic state, scientists have been buzzing over the promise of stem cell therapies. Stem cells can be coaxed to become any of the body’s cell types, so they could potentially replace diseased or missing cells in conditions such as diabetes or Alzheimer’s. And Yamanaka’s method also meant that these cells could be made from patients themselves, so they wouldn’t trigger dangerous immune rejections.

Now scientists led by Dr. Andras Nagy at Mount Sinai Hospital Lunenfeld-Tanenbaum Research Institute in Toronto report an exciting new advance that could push stem cells even closer to the clinic. In a series of papers in the journals Nature and Nature Communications, the group describes a new class of stem cell, which they called F class, that they generated in the lab.

The F class cells, says Nagy, have a few advantages over the Yamanaka-generated induced pluripotent stem cells, or iPS cells. While the iPS cells are created by using viruses to introduce four genes that reprogram the cells, Nagy’s team relied on a technique they developed several years ago using transposons—small pieces of DNA that can insert themselves into different parts of a genome. Unlike viruses, these transposons can be popped out of the genome if they’re no longer needed, and they don’t carry the potential risk of viral infection.

MORE Stem-Cell Research: The Quest Resumes

Nagy’s team found that the transposons were much more reliable vehicles for delivering the reprogramming genes exactly where they were needed to efficiently turn the clock back on the skin cells. What’s more, they could use the common antibiotic doxycycline to turn the four genes on and off; adding doxycycline to the cell culture would trigger the transposons to activate, thus turning on the genes, while removing the antibiotic would turn them off.

In this way, says Nagy, he was able to pump up the efficiency of the reprogramming process. Using the Yamanaka method, it was hit-or-miss whether the viruses would find their proper place in a cell’s genome, and more uncertainty over how effectively it could direct the cell to activate the four reprogramming genes. “F class cells are much more similar [in the culture dish], like monozygotic twins while iPS cells are more like brothers and sisters,” he says.

That consistency is a potential advantage of the transposon method, since any stem cell-based treatment would require a robust population of stem cells which can then be treated with the proper compounds to develop into insulin-making pancreatic cells to treat diabetes, or new nerve cells to replace dying ones in Alzheimer’s, or fresh heart muscle to substitute for scarred tissue after a heart attack.

MORE Stem Cell Miracle? New Therapies May Cure Chronic Conditions like Alzheimer’s

Nagy’s team also described, with the most detail to date, exactly how mature cells like skin cells perform the ultimate molecular feat and become forever young again when exposed to the four genes. They analyzed the changes in the cells’ DNA, the proteins they made, and more. “It’s similar to high definition TV,” he says. “We see things much better with much more detail. We expect that having that high resolution characterization will allow us to better understand what is happening during this process at the molecular level. And obviously that better understanding is going to affect what we can do with these cells to make them better, safer and more efficient in cell-based treatments in the future.”

That may be years away yet, especially since some experts say that transposons may pose their own risk of wreaking DNA havoc on a cell’s genome. But having another type of stem cell that could potentially churn out healthy cells and tissues to replaced diseased ones is a welcome development.

TIME health

Until 2014, This Man Was TIME’s Only Medical Person of the Year

TIME 1996: Dr. David Ho

For 2014, the Ebola Fighters have been selected. In 1996, the Man of the Year was AIDS researcher Dr. David Ho

“Some ages are defined by their epidemics,” wrote Philip Elmer-De Witt in TIME’s 1996 Man of the Year issue. The 14th century was the time of the bubonic plague. The 16th brought smallpox to the new world. In the early 20th century, influenza rampaged. “Today,” he wrote back then, “we live in the shadow of AIDS–the terrifyingly modern epidemic that travels by jet and zeros in on the body’s own disease-fighting immune system.”

The idea that a virus or bacterium can change the world — and that the men and women who fight them can too — is no less true now than it was then. On Wednesday, TIME announced that the Ebola Fighters have been named the Person of the Year for 2014.

As TIME’s Editor Nancy Gibbs notes, this year’s Ebola outbreak has brought forward heroes while raising the question of how the world can turn their personal sacrifices into new ways to fight the virus, to respond to epidemics and to care for those who need it most.

And though AIDS and Ebola remain two of the most frightening diseases on earth, looking back at 1996’s Man of the Year cover story can bring at least a little hope that those questions stand a chance of being answered. (There were theoretical medical researchers included in the 1960 Men of the Year issue, honoring U.S. scientists, but their work as doctors was not the focus of the story; Dr. Ho is the only Man of the Year prior to 2014 selected specifically for his work with a disease.) At the time, AIDS was a death sentence — but Ho, by successfully lowering the virus count in patients who received a combination of new and powerful drugs when they’d only just been infected, helped change the way the medical community looked at HIV and AIDS.

Nearly two decades later, though an AIDS vaccine is still not a reality, progress has been substantial. AIDS researchers have found their answers to many of the questions Ebola fighters face today. Treatment protocols are well established (if not applied equally all over the world). Survival is no longer miraculous. It’s possible to prevent transmission. And, just this winter, TIME took a look at the state of AIDS in San Francisco and found that, against what would have once seemed impossible odds, the city has the elimination of the disease in its sights.

Dr. Ho continues to direct the Aaron Diamond AIDS Research Center; in 2010, TIME profiled him again and found that he was still pioneering new ways of treating the disease. That tireless work by Ho and his colleagues is one of the reasons AIDS is no longer a defining disease of our time — and if he demonstrates that devotion and dedication can make a difference, that’s just one more reason to honor the Ebola fighters.

Read the full story about Dr. David Ho, here in the TIME Vault: Man of the Year, Dr. David Ho

TIME health

How the Mystery of AIDS Created Dangerous Myths

SIDA
Michel Setboun—Gamma-Rapho / Getty Images Microscope view of HIV, 1985

Dec. 10, 1981: The New England Journal of Medicine publishes a series of articles about a new disease that appears to target gay men

The early days of the AIDS epidemic were dangerous not just because a killer virus was sweeping across America, but because the mysterious syndrome spawned its own damaging myths.

On this day, Dec. 10, in 1981, the New England Journal of Medicine published three landmark articles and an editorial attempting to make sense of the deadly immune deficiency, which had been identified a scant six months earlier. By December, according to the BBC, the condition had been found in 180 Americans and killed 75, nearly all of them gay men.

Doctor Michael Gottlieb was among the first to recognize the chilling threat the crisis posed. When the epidemic began, 33 years ago, Gottlieb himself was 33 and an assistant professor of immunology at the UCLA Medical Center, eagerly searching for interesting “teaching cases,” according to a profile in the American Journal of Public Health.

One case that caught his attention was a harbinger of the devastation to come: a young gay man with an array of serious health problems more common to organ transplant patients than otherwise robust young people. Gottlieb and his fellow immunologists found that the man had virtually none of the “helper” cells that fight infection. After coming across several similar cases, the doctor suspected that some new, unknown virus was responsible. He told the editor of the New England Journal of Medicine that it might be “a bigger story than Legionnaire’s disease.”

To warn the medical community, Gottlieb put out his preliminary findings in the weekly report issued by the U.S. Centers for Disease Control and Prevention. By the time the journal article came out in December, other doctors from around the country had reported similar cases and were hunting for a cause.

One early theory pegged the spread of the disease — which the CDC named AIDS — to a club drug called “poppers,” although the correlation quickly broke down. New evidence that the virus was transmitted through bodily fluids emerged when heterosexual drug users began reporting symptoms, apparently after sharing dirty needles.

By then, however, hysteria over the agonizing illness had led to a proliferation of myths about its transmission. Those myths lingered long after they were disproved, adding another layer of stigma for the syndrome’s victims.

For example, in 1988 — by which time AIDS was well enough understood to make such claims preposterous — a sensationalistic book, Crisis: Heterosexual Behavior in the Age of AIDS, stirred new panic with old assertions about how the syndrome was spread. According to TIME’s review of the book, the authors suggested that contracting AIDS was as easy as using the toilet after someone with the virus, being bitten by the same mosquito or even getting to second base. This last was meant as a literal warning to baseball players, not a metaphor for heavy petting: a player could catch the virus by sliding onto the base “if, by chance, an infected player has bled onto it,” the book warned.

When confused — and terrified — callers jammed AIDS hotlines, one epidemiologist fumed, “This is the AIDS equivalent of shouting ‘Fire!’ in a crowded theater.”

Read more about the early search for the HIV virus, here in TIME’s archives: Hunting for the Hidden Killers

TIME medicine

Genetic Screening Saved This Baby’s Life

Researchers say sequencing genomes can lead to quicker diagnoses and effective treatments for more than half of children affected by brain disorders

Mya Burkhart was only six months old when she went into cardiac arrest. Fortunately, she was in the hospital when it happened, brought there by her parents because she had trouble breathing. It was her eighth or ninth visit to the emergency room for her respiratory problems, but each time the doctors had sent the Burkharts home with more questions than answers.

Mya wasn’t developing at the normal rate. She couldn’t lift her head and wasn’t responding to people and things around her. Doctors thought she might have a muscle disorder, but her other symptoms did not fit with that diagnosis.

After her heart scare, Mya spent three weeks, including her first Christmas, in the ICU on a ventilator. “I couldn’t pick her up or anything,” says her mother Holly. Still unable to solve the mystery of what was ailing her, the doctors finally suggested she have her genome tested. Maybe, they hoped, her DNA would offer some clues about why she wasn’t growing normally.

MORE: The DNA Dilemma: A Test That Could Change Your Life

Holly knew the test was still in the research stages, and that there was a chance that even it might not yield any more answers about her daughter’s condition. “At that point, I just wanted to try anything to find out what was wrong with her,” she says. It boiled down to balancing a chance that their baby would live or die.

Genetic screening, especially whole-genome screening in which people can learn about their possible risk for certain diseases, remains controversial, since the information is neither definitive nor always accurate. In most cases, genes can only predict, with a limited amount of certainty, whether a disease such as breast cancer or Alzheimer’s looms in a person’s future. As the Food and Drug Administration (FDA) contemplates the merits and efficacy of such screening, some doctors and researchers are using it with great success, according to a new study published in the journal Science Translational Medicine.

Researchers at Children’s Mercy Hospital in Kansas City, where Mya was treated, say that for 100 families, including the Burkharts, with children affected by either unknown disorders or brain abnormalities, genome screening helped 45% receive a new diagnosis, and guided 55% to a different treatment for their child’s disorder. Of the 100 families, 85 had been going from doctor to doctor in search of a diagnosis for an average of six and a half years.

“I was surprised by how many cases we found where a specific intervention can make a difference,” says Sarah Soden from the Center for Pediatric Genomic Medicine at Children’s Mercy and the study’s lead author. “For me it’s compelling enough to push the envelope and get younger kids diagnosed.”

MORE: Faster DNA Testing Helps Diagnose Disease in NICU Babies

In Mya’s case, her genome revealed a mutation in a gene responsible for transporting citrate; without it, her cells could not get the energy they needed. So far, only 13 babies have been confirmed with the condition, and all died before their first birthday after having seizures and respiratory infections. Once the genetic analysis revealed the deficiency, however, Mya was started on citrate supplements. She’s now 18 months old, having already lived nearly twice as long as the other confirmed cases. She has some developmental delays but she has not had any seizures and managed to avoid getting any serious respiratory infections.

Their success at Children’s Mercy are encouraging Soden and the study’s senior author, Dr. Stephen Kingsmore, to push ahead and determine how such screening can benefit more babies. About 5% of the 4 million babies born in the U.S. each year are admitted to the neonatal intensive care unit (NICU), and between those who are born with a genetic disorder and those who may have adverse drug interactions, he and his team anticipate that about 30%, or 60,000, may benefit from the personalized screening they offer.

For now, he and his team are targeting babies like Mya who are sick almost from the minute they enter the world, with symptoms and abnormalities that doctors simply cannot explain. For them, the screening can save families from uncertainty as well as the financial burden of having many different experts perform many different tests looking for a diagnosis. The average genetic sequencing for newborns costs around $5,000, but the average cost of a night’s stay in the Neonatal Intensive Care Unit (NICU) hovers around $8,000, and most babies spend days, if not weeks, in the units awaiting a diagnosis.

Kingsmore received a $1.5 million grant from the NIH to expand the screening program to other institutes, and he has reached out to hospitals in Florida, at the University of Maryland and in Oklahoma City to test the strategy in more babies. “If we can decrease the length of stay in the NICU it could certainly lead to huge potential cost savings,” says Dr. Alan Shuldiner, associate dean of personalized medicine at the University of Maryland.

In the latest study, Soden says that on average, families spent more than $30,000 on genetic testing alone to figure out what was ailing their babies; those who had their genomes screened paid about $3,000 for an answer.

The key to Kingsmore’s success is a system that starts with a doctor punching in a newborn’s baffling symptoms and ends with a genetic readout. The “magic juice,” as he calls it, is a database of 10,000 symptoms that typically affect infants, from simple coughs and fevers and enlarged hearts to all manner of abnormal lab readings. The baby’s unique combination of these symptoms is mapped onto the 3,000 genes that experts have so far connected to about 4,000 diseases. “No physician on the planet earth could carry that database around in his head,” says Kingsmore. But that’s what desperate parents, whose babies’ lives are at stake, expect them to do. So Kingsmore’s program accomplishes the feat, spitting out, in rank order, a list of potential genetic diagnoses. That targeted tally of diseases then directs doctors to focus on a much more manageable list of 10 or, at the most, 50 genes (from a possible 20,000 or so) that could be mutated and responsible for the baby’s condition.

While there is no argument that such testing can save lives, the more challenging question is who should be tested, and when. There is also still debate among those in the genetics and medical communities about how to interpret genomic data. “Some people would argue that he is still reporting his experimental findings, and moving too soon from the research arena into the clinical arena,” says Dr. Edward McCabe, chief medical officer of the March of Dimes.

Ethicists are concerned about the coerciveness inherent in any hand extended to parents whose babies would otherwise die; no matter how carefully and comprehensively doctors word their request, parents in that situation may not fully process the risks and benefits and be unable to provide a truly informed consent. What if the baby falls into the minority for whom the testing doesn’t yield a diagnosis or treatment? When faced with inevitable death on the one hand, and a chance, however, small, of avoiding that death on the other, can there ever really be a choice?

The stakes are especially high since in some cases, the disorders won’t lead to established and approved treatments, but experimental ones without known risks and benefits. But as the value of such testing becomes more obvious, more centers may consider sequencing more newborns’ genes. “These babies, because they are brand new, are salvageable,” says Kingsmore. “Many patients we see with genetic illnesses already have ravaged organs. In contrast, with newborn babies we have the opportunity to halt a disease early in its progression,” he says.

“I think this testing is definitely something that everybody should consider,” Holly Burkhart says. “Without it, we probably never would have figured out what was wrong with Mya. We probably would be in the same place we were a few months ago.” Instead, Mya is now smiling at her mom and making progress. “The testing helped us find answers, and tell us where we need to go from here,” she says.

TIME Innovation

Five Best Ideas of the Day: December 8

The Aspen Institute is an educational and policy studies organization based in Washington, D.C.

1. A new crowdfunded software tool for reporting sexual assault can reduce stigma and protect survivors.

By Shafaq Hasan in Nonprofit Quarterly

2. Millions of discarded laptop batteries could light homes in the developing world.

By David Talbot in the MIT Technology Review

3. A long overdue transparency plan for clinical trials will finally open results to the medical community and the public.

By Julia Belluz in Vox

4. Without role models or a road map through the upper ranks, women are leaving the tech industry at the mid-career point in droves.

By Sue Gardner in the Los Angeles Times

5. A new plan to drop strips of prairie into cropland helps preserve soil and battle climate change.

By Dylan Roth in Iowa State Daily

The Aspen Institute is an educational and policy studies organization based in Washington, D.C.

TIME Ideas hosts the world's leading voices, providing commentary and expertise on the most compelling events in news, society, and culture. We welcome outside contributions. To submit a piece, email ideas@time.com.

TIME medicine

That Flu Shot You Had May Not Work This Year

Flu vaccines
David Cheskin—PA Wire/AP

You should still get vaccinated

The Centers of Disease Control and Prevention (CDC) have warned doctors that flu vaccines may not be effective against the most common strain of flu circulating in the U.S..

According to Reuters, the U.S. health agency issued an advisory to doctors Wednesday saying that of the flu samples they had taken between October 1 and November 22, less than half were good matches for the current flu shots.

The flu shots will still protect against certain strains of the flu, and can help reduce the risk of complications even among the strains that have mutated.

[Reuters]

 

TIME health

Plastic and Permanent: The Artificial Heart’s Debut

First Artificial Heart Implantation
Ravell Call—Getty Images Barney Clark receives the first artificial heart implant Dec. 2, 1982, in Salt Lake City

Dec. 2, 1982: Doctors implant the first permanent artificial heart in a human, Barney Clark, who lives 112 days with it

Barney Clark’s heart was made of plastic — and instead of beating, it whooshed.

The 61-year-old retired dentist was in an advanced stage of cardiomyopathy, a progressive weakening of the heart muscle, when he became the first recipient of a permanent artificial heart on this day, Dec. 2, in 1982.

Heart transplants were already being done to prolong lives, but in a limited, last-resort way. Surgeons accomplished the first human-to-human transplant in South Africa in 1967, when a man with severe heart damage received the heart of a 25-year-old woman who had died in a car crash. He survived 18 days. In 1977, after new immunosuppressant drugs dramatically increased the odds of survival, the first recipient of a heart transplant at Columbia University’s Medical Center — one of only three institutions in the country performing the surgery at the time — survived 14 months.

But Clark was 11 years too old to be a candidate for a heart transplant, according to the criteria U.S. surgeons had by then agreed on. His only shot at survival was Dr. Robert Jarvik’s pneumatically-powered heart. The Jarvik 7, as it was called, comprised two plastic pumps powered by compressed air, which required the patient to be hooked up at all times to a rolling console the size and weight of a refrigerator. The artificial heart could pump blood through the body at 40 to 120 pulses per minute, but it replaced the telltale heartbeat with a soft clicking sound followed by a whoosh.

Clark knew what he was in for: before agreeing to the operation, he first toured a facility where Jarvik’s hearts were keeping several sheep and calves alive, including a calf named Tennyson who set the survival record of 268 days, according to TIME.

He met the requirements for the surgery by having a fatal heart condition, with no other treatment alternatives, as well as a strong will to live. By the time of the surgery, he was nearly dead already: his heart was pumping a liter of blood per minute, or a fifth the normal rate.

The surgery was considered a success, since Clark went on to live another 112 days. A surgeon told TIME that his color had changed, from blue to pink, after more oxygen infused his blood. There were hitches, however. A week after the surgery, he suffered a series of seizures his doctors blamed on an imbalance of fluids and salts. Following the seizures, he was often disoriented, and sometimes believed he was still a dentist in Seattle.

He never left the hospital after his transplant, and ultimately died of “circulatory collapse and secondary multi-organ system failure” triggered by an infection that was likely the result of a blood transfusion, according to his obituary in the New York Times.

Later recipients fared somewhat better with the Jarvik 7. William Schroeder lived a record 620 days with one, although his quality of life was poor after he suffered serious strokes within the first three weeks. Another recipient, Leif Stenberg, made remarkable progress with his new heart, and lived 229 days before suffering a fatal stroke.

Stenberg’s renewed vigor was a triumph fraught with unexpected philosophical considerations. Long suspected of being a powerful Swedish crime boss, he was never convicted of any crime, partly because his health problems delayed a trial on charges of tax evasion. But the transplant led to a new delay, since Swedish law defined death as the moment when one’s heart stopped beating. Stenberg’s attorneys, therefore, argued that he should not have to stand trial, since he was already dead.

Read the full report on Barney Clark’s operation from 1982, here in the TIME Vault: Living on Borrowed Time

TIME health

World AIDS Day: The History of a Virus in 7 Stories

Track the history of the disease through the pages of TIME

Dec. 1 has been World AIDS Day since 1988 — but though the awareness and activism around the diseases has changed drastically during the years between then and now.

To see just how much our understanding and attitudes have evolved, take a look back at TIME’s coverage of AIDS through these seven essential stories:

Hunting for the Hidden Killers by Walter Isaacson, Jul. 4, 1983

This 1983 cover story wasn’t the first time AIDS appeared in the pages of TIME — in 1982, an article had explained the new “plague” to readers — but the tale of the “disease detectives” at the Centers for Disease Control and the National Institutes of Health highlights just how little was known about the disease:

Based on what is known so far, two theories have emerged. One is that AIDS is caused by a specific agent, most probably a virus. “The infectious-agent hypothesis is much stronger than it was months ago,” says Curran, reflecting the prevailing opinion at CDC. NIH Researcher Fauci, who staunchly believes that the culprit is a virus, has been collecting helper T-cells from AIDS victims to look for bits of viruses within their genetic codes. So far, however, this and other complex methods of detecting viruses have yielded nothing conclusive. Suspicion focuses on two viruses: one is a member of the herpes family called CMV; the other, called human T-cell leukemia virus, or HTLV, is linked to leukemia and lymphoma.

The other theory is that the immune system of AIDS victims is simply overpowered by the assault of a variety of infections. Both drug users and active homosexuals are continually bombarded by a gallery of illnesses. Repeated exposure to the herpes virus, or to sperm entering the blood after anal intercourse, can lead to elevated levels of suppressor Tcells. The immune system eventually is so badly altered that, as one researcher puts it, “the whole thing explodes.” Other experts combine the two theories, speculating that a new virus may indeed be involved, but that it only takes hold when a combination of factors affects the potential victim, such as an imbalanced immune system or certain genetic characteristics.

AIDS: A Growing Threat by Claudia Wallis, Aug. 12, 1985

As AIDS spread, so did awareness and knowledge — as well as paranoia:

Despite their physical ordeal, many AIDS sufferers say that the worst aspect of their condition is the sense of isolation and personal rejection. “It’s like wearing the scarlet letter,” says a 35-year-old Harvard-educated lawyer who was forced out of a job at a top Texas law firm. “When people do find out,” he says, “there is a shading, a variation in how they treat me. There is less familiarity. A lot less.” Sometimes the changes are far from subtle, according to Mark Senak, a lawyer at the Gay Men’s Health Crisis, a volunteer organization that helps AIDS patients in New York. “They’ll come out of the hospital, and their roommate has thrown them out–I mean literally,” he says. “Their clothes will be on the street.” Rejection of this sort is not unique to gay men. Senak cites the case of a heterosexual woman with AIDS whose husband and family refused to take her back home from the hospital.

Invincible AIDS by Christine Gorman, Aug. 3, 1992

As the ’90s began, the hope that modern science could quickly conquer AIDS began to fade:

Wars are usually launched with the promise of a quick victory, with trumpets primed never to sound retreat. And the campaign against AIDS was no exception. Soon after researchers announced in the mid-1980s that they had discovered the virus that causes AIDS, U.S. health officials confidently crowed that a vaccine would be ready in two years. The most frightening scourge of the late 20th century would succumb to a swift counterattack of human ingenuity and high technology.

But no one was making any victory speeches last week in Amsterdam, where more than 11,000 scientists and other experts gathered for the Eighth International AIDS Conference. The mood was somber, reflecting a decade of frustration, failure and mounting tragedy. After billions of dollars of scattershot albeit intensive research and halfhearted prevention efforts, humanity may not be any closer to conquering AIDS than when the quest began.

As if by Magic by Steve Wulf, Feb. 12, 1996

For more than a decade, AIDS had been a death sentence — but suddenly survival had a celebrity face. The NBA’s Magic Johnson was back in action:

If there was a bittersweet feeling to Johnson’s return last week, it came from the realization that his exile from the game had been largely unnecessary. When Magic announced to the world on Nov. 7, 1991, that he had contracted the AIDS virus, it seemed to many that he was pronouncing his own death sentence. Michael Cooper, a teammate at the time, left the press conference crying. Johnson had to quit basketball then, supposedly for the sake of his own health and definitely for the peace of mind of his peers. He made cameo appearances, first at the 1992 N.B.A. All-Star Game and then as a member of the USA’s Dream Team in the Barcelona Olympics, but when he tried to make a comeback in the fall of ’92, the fears of some outspoken N.B.A. players forced him to call it off.

But so much has happened in four years, in both AIDS research and AIDS education.

Hope With an Asterisk by Richard Lacayo, Dec. 30, 1996

In 1996, TIME named Dr. David Ho, an AIDS researcher, the Man of the Year — and, in a series of accompanying stories, explained why. That year, a cocktail of three drugs had changed what it meant to be an HIV patient:

In the history of the epidemic, there has never been a moment as intricate as this one. AIDS once again, as in the first years after it appeared, presents a predicament so new that no one is sure how to talk about it. When we say protease inhibitors work, what do we mean? Whom do they work for, how well and for how long? The only thing we know with certainty is that the conventions of language and sentiment that fit an earlier moment of AIDS, meaning all the years when death was at the end of every struggle, are unsuited to this one, when nothing is a foregone conclusion. Something powerful is happening. The new prospects for effective treatment insist that despair is an outmoded psychological reflex. Yet among people who live with AIDS, optimism is a suspicious character. Too many bright hopes of the past didn’t pan out. So this is a moment in which, for anyone with feeling and judgment, feeling and judgment are unsettled.

Death Stalks a Continent by Johanna McGeary, Feb. 12, 2001

In the U.S., the possibility was on the horizon: AIDS could be perhaps become a manageable chronic illness, or at least a rare disease rather than a plague. But that hopeful attitude was not a worldwide phenomenon, as a lengthy and moving cover story about African patients made clear:

AIDS in Africa bears little resemblance to the American epidemic, limited to specific high-risk groups and brought under control through intensive education, vigorous political action and expensive drug therapy. Here the disease has bred a Darwinian perversion. Society’s fittest, not its frailest, are the ones who die–adults spirited away, leaving the old and the children behind. You cannot define risk groups: everyone who is sexually active is at risk. Babies too, unwittingly infected by mothers. Barely a single family remains untouched. Most do not know how or when they caught the virus, many never know they have it, many who do know don’t tell anyone as they lie dying. Africa can provide no treatment for those with AIDS.

The End of AIDS by Alice Park, Dec. 1, 2014

The current issue of TIME presents pretty much the opposite picture from the one seen a mere three decades earlier. Whereas the syndrome’s first mentions were full of confusion and fear, today’s AIDS story — the tale of a program in San Francisco that aims to get everyone who’s positive onto medication — is about control and opportunity:

More than three decades later, the disease has killed over 650,000 Americans, and the HIV/AIDS landscape, thankfully, has changed. At its peak, there were 50,000 deaths from the virus per year; now the number is 15,000. Lately, the rate of new HIV infections has stabilized at about 50,000 annually, and more than 1 million people in the U.S. are now living with an HIV diagnosis.

Those trends are making it possible for public-health experts to shift the conversation toward reducing, and even eliminating, HIV infections. More people are living with the virus–successfully controlling it with medication–and far fewer have the immune-system crashes, cancers and infections that can come with full-blown AIDS.

And the face of HIV today is a world away from the gaunt faces and wasted spirits brought to life in Tony Kushner’s Angels in America and by Tom Hanks in Philadelphia. The reality is that it’s now possible to live, for nearly an average lifetime, without any obvious physical evidence of an HIV infection.

Read more: The Photo That Changed the Face of AIDS

TIME health

How Dr. Alzheimer Discovered a Disease in a Mental Asylum

Alois Alzheimer
Apic / Getty Images Alois Alzheimer (1864-1915)

The unusual case seemed to stick out and the psychiatrist sensed that there was something special about Auguste. Dr. Alois Alzheimer decided that he should see Auguste for himself

History News Network

This post is in partnership with the History News Network, the website that puts the news into historical perspective. The article below was originally published at HNN.

Carl didn’t know what was happening to his wife. The German railway clerk from Morfelder Landstasse and his wife Auguste had been happily married for twenty-eight years. They had one daughter, Thekla, and their marriage had always been harmonious; that is, until one Spring day in 1901 when Auguste suddenly exhibited signs of jealousy.

Auguste accused Carl of going for a walk with a female neighbor, and since then, she had been increasingly mistrustful. Carl thought that this sudden jealousy was unfounded. Over the next several months, Auguste’s memory began to fade. The once orderly and industrious homemaker was making uncharacteristic mistakes in preparing home meals — a task that she had probably performed countless times. She wandered aimlessly around the apartment, leaving housework unfinished. She became convinced that a cart driver who frequented their house was trying to harm her and that people were talking about her. Without explanation, she began to hide various objects around the house. The couple’s neighbors sometimes discovered Auguste ringing their doorbells for no reason.

Prior to this change, Auguste had never been seriously ill. She was an otherwise healthy 51-year old woman who did not drink alcohol nor suffered from any mental illness. By November of 1901, Carl was at wit’s end. He had no choice but to take his wife to the local mental asylum. The physician’s admittance note described her as suffering from a weak memory, persecution mania, sleeplessness, and restlessness that rendered her unable to perform physical or mental work.

The following day, the senior physician at the Asylum for the Insane and Epileptic in Frankfurt am Main came across Auguste’s clinical notes. The unusual case seemed to stick out and the psychiatrist sensed that there was something special about Auguste. It was the case that he was waiting for. Dr. Alois Alzheimer decided that he should see Auguste for himself.

Over the next several months, Dr. Alzheimer interviewed and examined Auguste, whose condition continued to deteriorate. He asked her to name common objects, perform simple arithmetic, tell him where she lived, what year it was, the color of snow, the sky, grass, and so on. Alzheimer maintained a detailed record and even arranged for Auguste to be photographed. One photo reveals a woman with a deeply furrowed forehead and heavy bags under her eyes. She was wearing a white hospital gown and her face had a tired, blank expression, with perhaps a hint of fear. Her hands were draped over her raised knees, with the long fingers securely interlocked.

What struck Dr. Alzheimer was Auguste’s relatively young age. He had seen cases of mental deterioration in much older patients and had theorized that age-related thickening of the brain’s blood vessels led to brain atrophy. It was unusual, however, to see the condition in a person who was only fifty-one years old. Dr. Alzheimer had only encountered one other case similar to Auguste’s. The autopsy findings on that patient revealed shrinkage in specific brain cells but no significant blood vessel thickening.

Dr. Alzheimer continued his daily visits and long conversations with Auguste. There was no cure, of course, and the limited treatments included the use of sedatives and warm baths. At times, Auguste had to be placed in isolation after she groped faces and struck other patients in the clinic. She wandered aimlessly, sometimes screamed for hours, and became increasingly hostile. By February of 1902, her condition had advanced to the point that long conversations and physical examinations became impossible.

On April 8, 1906, after nearly five years of progressive mental and physical decline, Auguste died. The official cause of death was blood poisoning due to bedsores. Dr. Alzheimer suspected that behind her mental illness was a strange disease, and that perhaps examining her brain would offer some clues. When he examined the brain sections under the microscope, his suspicion was confirmed. Dr. Alzheimer described changes in the neurofibrils — the protein filaments found in brain cells. He also saw peculiar deposits that he referred to a “millet seed-sized lesions.” These pathologic findings — now known as neurofibrillary tangles and amyloid deposits – characterize the brains of Alzheimer’s Disease patients.

Dr. Alzheimer’s discovery was not immediately well received. In fact, the first time he presented Auguste’s case and autopsy findings during a German Psychiatry conference in 1906, the reception from the audience was rather cold. This was the time when psychoanalysis and the Freudian views on the relationship between childhood trauma and mental illness were, in today’s parlance, the “trending” topics in psychiatry. Correlating mental or neurologic disorders with histopathologic findings was not yet firmly established nor accepted. Ninety years later, in 1998, researchers re-examined Auguste’s original brain sections and confirmed the presence of neurofibrillary tangles and amyloid plaques.

Emil Kraepelin, one of the most prominent psychiatrists in the early 1900s, first mentioned the term ‘Alzheimer’s Disease’ in the 1910 edition of his textbook on psychiatry. The disease was of course still poorly understood, but one of the most famous medical eponyms was born.

Today, there are an estimated five million Americans diagnosed with Alzheimer’s Disease. The number is expected to rise as the population ages. There is no cure, and the burden on the afflicted as well as caregivers remains tremendous. The economic burden is also substantial, with healthcare costs for dementia in general estimated to be over $200 billion dollars in 2010. Researchers are on a quest to find effective treatment in areas that include stem cell and gene therapy.

Rod Tanchanco is a physician specializing in Internal Medicine. He writes about events and people in the history of medicine. His personal blog is at talesinmedicine.com.

References

Maurer K. Alzheimer : the life of a physician and the career of a disease. New York: Columbia University Press; 2003.

Graeber MB, Kösel S, Grasbon-Frodl E, Möller HJ, Mehraein P. Histopathology and APOE genotype of the first Alzheimer disease patient, Auguste D. Neurogenetics. 1998;1(3):223–8

TIME Behind the Picture

The Photo That Changed the Face of AIDS

LIFE.com shares the story behind one of the most harrowing and controversial photographs to emerge from the global pandemic

In November 1990 LIFE magazine published a photograph of a young man named David Kirby — his body wasted by AIDS, his gaze locked on something beyond this world — surrounded by anguished family members as he took his last breaths. The haunting image of Kirby on his death bed, taken by a journalism student named Therese Frare, quickly became the one photograph most powerfully identified with the HIV/AIDS epidemic that, by then, had seen millions of people infected (many of them unknowingly) around the globe.

Here, a quarter-century later, LIFE.com shares the deeply moving story behind that picture, along with Frare’s own memories of those harrowing, transformative years.

“I started grad school at Ohio University in Athens in January 1990,” Frare told LIFE.com. “Right away, I began volunteering at the Pater Noster House, an AIDS hospice in Columbus. In March I started taking photos there and got to know the staff — and one volunteer, in particular, named Peta — who were caring for David and the other patients.”

David Kirby was born and raised in a small town in Ohio. A gay activist in the 1980s, he learned in the late Eighties — while he was living in California and estranged from his family — that he had contracted HIV. He got in touch with his parents and asked if he could come home; he wanted, he said, to die with his family around him. The Kirbys welcomed their son back.

[See all of TIME.com’s coverage of HIV/AIDS]

Peta, for his part, was an extraordinary (and sometimes extraordinarily difficult) character. Born Patrick Church, Peta was “half-Native American and half-White,” Frare says, “a caregiver and a client at Pater Noster, a person who rode the line between genders and one of the most amazing people I’ve ever met.”

“On the day David died, I was visiting Peta,” Frare, who today lives and works in Seattle, told LIFE. “Some of the staff came in to get Peta so he could be with David, and he took me with him. I stayed outside David’s room, minding my own business, when David’s mom came out and told me that the family wanted me to photograph people saying their final goodbyes. I went in and stood quietly in the corner, barely moving, watching and photographing the scene. Afterwards I knew, I absolutely knew, that something truly incredible had unfolded in that room, right in front of me.”

“Early on,” Frare says of her time at Pater Noster House, “I asked David if he minded me taking pictures, and he said, ‘That’s fine, as long as it’s not for personal profit.’ To this day I don’t take any money for the picture. But David was an activist, and he wanted to get the word out there about how devastating AIDS was to families and communities. Honestly, I think he was a lot more in tune with how important these photos might become.”

Frare pauses, and laughs. “At the time, I was like, Besides, who’s going to see these pictures, anyway?

Over the past 20 years, by some estimates, as many as one billion people have seen the now-iconic Frare photograph that appeared in LIFE, as it was reproduced in hundreds of newspaper, magazine and TV stories — all over the world — focusing on the photo itself and (increasingly) on the controversies that surrounded it.

Frare’s photograph of David’s family comforting him in the hour of his death earned accolades, including a World Press Photo Award, when published in LIFE, but it became positively notorious two years later when Benetton used a colorized version of the photo in a provocative ad campaign. Individuals and groups ranging from Roman Catholics (who felt the picture mocked classical imagery of Mary cradling Christ after his crucifixion) to AIDS activists (furious at what they saw as corporate exploitation of death in order to sell T-shirts) voiced outrage. England’s high-profile AIDS charity, the Terrence Higgins Trust, called for a ban of the ad, labeling it offensive and unethical, while powerhouse fashion magazines like Elle, Vogue and Marie Claire refused to run it. Calling for a boycott of Benetton, London’s Sunday Times argued that “the only way to stop this madness is to vote with our cash.”

“We never had any reservations about allowing Benetton to use Therese’s photograph in that ad,” David Kirby’s mother, Kay, told LIFE.com. “What I objected to was everybody who put their two cents in about how outrageous they thought it was, when nobody knew anything about us, or about David. My son more or less starved to death at the end,” she said, bluntly, describing one of the grisly side effects of the disease. “We just felt it was time that people saw the truth about AIDS, and if Benetton could help in that effort, fine. That ad was the last chance for people to see David — a marker, to show that he was once here, among us.”

David Kirby passed away in April 1990, at the age of 32, not long after Frare began shooting at the hospice. But in an odd and ultimately revelatory twist, it turned out that she spent much more time with Peta, who himself was HIV-positive while caring for David, than she did with David himself. She gained renown for her devastating, compassionate picture of one young man dying of AIDS, but the photographs she made after David Kirby’s death revealed an even more complex and compelling tale.

Frare photographed Peta over the course of two years, until he, too, died of AIDS in the fall of 1992.

“Peta was an incredible person,” Frare says. Twenty years on, the affection in her voice is palpable. “He was dealing with all sorts of dualities in his life — he was half-Native American and half-White, a caregiver and a client at Pater Noster, a person who rode the line between genders, all of that — but he was also very, very strong.”

As Peta’s health deteriorated in early 1992 — as his HIV-positive status transitioned to AIDS — the Kirbys began to care for him, in much the same way that Peta had cared for their son in the final months of his life. Peta had comforted David; spoken to him; held him; tried to relieve his pain and loneliness through simple human contact — and the Kirbys resolved to do the same for Peta, to be there for him as his strength and his vitality faded.

Kay Kirby told LIFE.com that she “made up my mind when David was dying and Peta was helping to care for him, that when Peta’s time came — and we all knew it would come — that we would care for him. There was never any question. We were going to take care of Peta. That was that.

“For a while there,” Kay remembers, “I took care of Peta as often as I could. It was hard, because we couldn’t afford to be there all the time. But Bill would come in on weekends and we did the best we could in the short time we had.”

Kay describes Peta, as his condition worsened in late 1991 and 1992, as a “very difficult patient. He was very clear and vocal about what he wanted, and when he wanted it. But during all the time we cared for him, I can only recall once when he yelled at me. I yelled right back at him — he knew I was not going to let him get away with that sort of behavior — and we went on from there.”

Bill and Kay Kirby were, in effect, the house parents for the home where Peta spent his last months.

“My husband and I were hurt by the way David was treated in the small country hospital near our home where he spent time after coming back to Ohio,” Kay Kirby said. “Even the person who handed out menus refused to let David hold one [for fear of infection]. She would read out the meals to him from the doorway. We told ourselves that we would help other people with AIDS avoid all that, and we tried to make sure that Peta never went through it.”

“I had worked for newspapers for about 12 years already when I went to grad school,” Therese Frare says, “and was very interested in covering AIDS by the time I got to Columbus. Of course, it was difficult to find a community of people with HIV and AIDS willing to be photographed back then, but when I was given the okay to take pictures at Pater Noster I knew I was doing something that was important — important to me, at least. I never believed that it would lead to being published in LIFE, or winning awards, or being involved in anything controversial — certainly nothing as epic as the Benetton controversy. In the end, the picture of David became the one image that was seen around the world, but there was so much more that I had tried to document with Peta, and the Kirbys and the other people at Pater Noster. And all of that sort of got lost, and forgotten.”

Lost and forgotten — or, at the very least, utterly overshadowed — until LIFE.com contacted Frare, and asked her where the photo of David Kirby came from.

“You know, at the time the Benetton ad was running, and the controversy over their use of my picture of David was really raging, I was falling apart,” Frare says. “I was falling to pieces. But Bill Kirby told me something I never forgot. He said, ‘Listen, Therese. Benetton didn’t use us, or exploit us. We used them. Because of them, your photo was seen all over the world, and that’s exactly what David wanted.’ And I just held on to that.”

After the Benetton controversy finally subsided, Therese Frare went on to other work, other photography, freelancing from Seattle for the New York Times, major magazines and other outlets. While the world has become more familiar with HIV and AIDS in the intervening years, Frare’s photograph went a long way toward dispelling some of the fear and, at times, willful ignorance that had accompanied any mention of the disease. Barb Cordle, volunteer director at Pater Noster when David Kirby was there, once said that Frare’s famous photo “has done more to soften people’s hearts on AIDS than any other I have ever seen. You can’t look at that picture and hate a person with AIDS. You just can’t.”

[See more of Therese Frare’s work at FrareDavis.com]

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