An Inconvenient Cure
When Timothy Brown contracted HIV in the early 1990s, the virus was a death sentence. A cure 12 years later—the cure no scientist in the world believed existed at first—originated in the last place he would ever expect.
THE PART OF THIS STORY YOU MAY ALREADY KNOW is the stuff of news montages.
Somewhere between two planes crashing into the world’s financial center and a rover touching down on the red Martian dirt, future audiences gorging on the events that defined the early part of the twenty-first century will get a flash of a skinny man with thinning brown hair, reading glasses on the end of his nose. Either the words will appear on the screen or the man himself will be heard explaining that you are looking at the first person cured of HIV, a plague that spent 30 years killing millions around the globe.
What news archivist of the future could resist Tuesday, July 24, 2012, during the 19th International AIDS Conference in Washington, DC? The day before, then–secretary of state Hillary Clinton addressed the crowd, welcoming more than 20,000 attendees back to the United States, as the conference had not been held in this country since 1990—the year the plague had infected almost 161,000 Americans and claimed the lives of more than 120,000.
There had long been whispers in AIDS research circles and the occasional story in the press about the man cured via an obscure procedure in Germany—a bone marrow stem cell transplant to treat his acute myeloid leukemia that also rid his body of HIV.
That wasn’t the message delivered from the podium. No, Secretary Clinton said that while extraordinary progress had occurred in the past two decades, no cure had been achieved. Later that day, Bill Gates, whose foundation has made AIDS research a top priority, particularly in Africa, made his opinion clear. “If somebody could cure AIDS…that’s very much a long shot,” he told the audience. “It’s probably not in the cards anytime soon, which is why the treatment imperative is so dramatic.” Richard Horton, editor of the medical journal The Lancet, piled on. Global health blog Humanosphere reported that he told attendees, “This kind of language implies we are close to ending the epidemic, and it’s just not true. It’s a marketing strategy, and one that could backfire.”
So it was particularly bold, if somewhat jarring, when Timothy Brown gave a press conference the next day in an out-of-the-way room in DC’s Westin City Center hotel. “Let me be crystal clear: I am HIV negative. I am free of the virus.” Then, as if no one in the audience quite believed him, he added, “Despite what you may have read and heard recently in the media, I am cured of the AIDS virus.”
He followed that with the announcement that he would be dedicating his life and body to the sole purpose of developing a universal cure for AIDS.
How he got there would be a story for another time—a story that begins decades ago and halfway across the planet, if we’re talking the virus. If we’re talking the patient, it begins in the other Washington on—why not?—a bus.
(IMAGE: Timothy Brown’s senior portrait in the Ingraham High School 1984 yearbook)
Picture him. Small guy. Curly, brown hair. A public bus brings him from Edmonds, where he and his mother moved shortly after his freshman year, to North Seattle’s Ingraham High School. He sits alone, applying lipstick. It’s the early 1980s and one of Timothy Brown’s favorite musical acts is Culture Club. He wants to be Boy George. The confusion and disdain on the faces of his fellow passengers is obvious. Brown doesn’t care. He’ll never care.
“He was fearless,” recalls one of his best friends at the time, Elaine Fitch, who met Brown when they were 10 years old and their mothers joined the same singles group in a North Seattle church. At school, when someone tried to spread a rumor that he and a friend were gay and having sex together, Brown corrected the record. “He’s not gay,” he said, “but I am.”
Soon only his mother was in the dark about his orientation. Sometimes he went to Northgate mall, the first mall in America, to find other gay teens. It was secret and exciting, even after that time in the men’s room at Nordstrom when store security caught him with a fellow 17-year-old. The store called the police, and Brown sat with the other kid in a back office while the cop tried to reach Mrs. Brown. No answer. The other kid wasn’t so lucky. “Your son’s been arrested,” the cop told the other kid’s mother. “For what?” Brown could overhear the woman say through the receiver.
“For lewd conduct.”
“What was he doing?”
Released from custody, Brown slinked from the store and out onto the curb, where his mother waited as planned. He told her nothing but later wrote a four-page letter explaining to her what had happened. Except he lied. He wrote it was the first time.
“He was very promiscuous,” explains Fitch. “And all of us would caution him to at least be careful. And obviously he wasn’t.”
By 1984, the year Brown graduated from Ingraham, Seattle had already seen dozens of AIDS cases.
The idea was a long shot, one that no one had ever tried and that no one, not even Hütter’s colleagues, thought possible.
Acquired Immunodeficiency Syndrome first gripped the U.S. when gay men in New York, Los Angeles, and San Francisco inexplicably contracted and died from pneumocystis pneumonia. AIDS gobbled up T cells until a person’s immune system was nonexistent, leaving him or her vulnerable to a host of diseases. Researchers eventually identified the virus that caused the epidemic, HIV (human immunodeficiency virus), and its modes of travel: blood transfusions and sexual intercourse.
The first two Seattle AIDS cases appeared in 1982. By 1987 area physicians had diagnosed about 500 cumulative cases in King County. In 1989 the number jumped to 1,000 cases; 92 percent were attributed to transmission via gay male sex.
That early history is riddled with frustration, beginning with fights over who discovered the virus, who to blame for spreading it, and why no cure or even an effective treatment existed. ACT-UP (the AIDS Coalition to Unleash Power) kept the conversation kindled, advocating for HIV patients’ rights during a time when U.S. and global leaders turned a blind eye to the syndrome quickly taking the lives of thousands of gay men. Through nonviolent sit-ins and other forms of protest, ACT-UP pressured the Centers for Disease Control, the National Institutes of Health, and the Federal Drug Administration to respond more quickly to the epidemic.
Timothy Brown, now living in Seattle’s Capitol Hill in an apartment on Summit Ave, worked at a bank downtown, took business classes at Seattle University—courtesy of his employer—and, around 1989, joined the Seattle chapter of ACT-UP.
On Thursday, September 13, 1990, Brown and about 40 of his fellow activists disrupted a Nordstrom fashion show at the Sheraton Hotel and Towers downtown. “We’re here!” they chanted. “We’re queer. We’re not going shopping.”
The protestors showered the crowd with pamphlets that censured Nordstrom for its alleged poor treatment of gay employees and employees with HIV. (Among their demands was that the retailer extend benefits to domestic partners.) For another demonstration, ACT-UP filed into the office of then-mayor Charles Royer for a silent sit-in. Except the same guy who squashed a rumor at school by announcing he was gay couldn’t stay quiet for long. Brown broke the silence and loudly articulated ACT-UP’s message—until the others told him to shut up.
In 1990 he toured Europe with Elaine Fitch and another female friend. They explored England, France, Spain, and Greece for three months. Brown’s pursuit of sexual partners, says Fitch, made him a difficult travel companion. “Tim was just going out and meeting people, so there’d be nights where Sherry and I’d be tired, or we’d have to get up and travel someplace else the next day, and he’d go out.” And not return all night. On at least one occasion the women had to catch a train and arrange—via long-distance phone calls with Brown’s mother—to meet him somewhere in the next city on the itinerary. “I was really mad, because, you know, we generally assumed he was okay, but still, you’re in a foreign city, and he just didn’t come back.”
Brown returned to Seattle after three months, but the city had lost its shine. A year later he was living in Barcelona, where he says he “drank a lot of red wine and beer” before finally landing a position as an English teacher at a summer camp for kids. After his Syrian roommate caught him lying naked with a man in the living room and threatened to throw him off the balcony, he moved to Germany, where he worked as a translator.
All the while Brown maintained a robust if sometimes risky sex life: While he usually used condoms, occasionally he didn’t.
(Image: Josh Trujillo/Courtesy Fred Hutchinson Cancer Research CenterTimothy Brown returned to Seattle for a visit in June 2013, six years after his remarkable cure from the AIDS virus.)
In 1995, Elaine Fitch, attending law school in San Francisco, answered the telephone. It was Brown, now living in Berlin. He had tested positive for HIV.
“I was furious. Part of it was just the pain and fear,” Fitch recalls. “Just knowing the prevalence of HIV at that point and knowing how promiscuous he was… I remember crying and pounding on the wall. Just being really upset. Because at that point, it was a death sentence.”
An AIDS diagnosis in ’95, when nearly 20 million people worldwide had the virus, was just that. There was no reliable treatment, and the one drug that had proven effective, AZT, was actually killing some patients.
A former partner who also had AIDS told Brown, “You know, we probably only have two years to live.” Facing what he thought was certain demise, Brown decided to focus on his education and continued university studies in Berlin. He waited a year before telling his mother about the diagnosis, though, as she was in her own battle against breast cancer. This time he didn’t leave it to a letter. On a visit to Seattle, he invited her for a walk in a park. He broke the news on a bench. It was her worst fear about her son come true.
Luckily for Brown, a year after his diagnosis a new combination of AIDS treatments, a cocktail of drugs called antiretroviral therapy, was keeping the virus at bay for some patients. The mortality rates slumped off, and the infected were told they might live after all. For Brown, AIDS became an inconvenient—14 pills a day—but manageable chronic illness.
He wouldn’t consider himself lucky for long. In 2006 he started to feel sluggish and constantly tired. Tests revealed he had acute myeloid leukemia. If he was to survive, chemotherapy would have to begin immediately.
During Brown’s second round of chemo at Berlin’s Charité Hospital, his doctor, Gero Hütter, approached him in the hall and said that he’d like to take a blood sample to send to the bone marrow donor bank. The request sur-prised Brown. Chemo, not a bone marrow transplant, had been the decided-upon treatment for his leukemia.
The doctor had an idea.
A receptor known as CCR5 opens the door for HIV to enter the immune system of an infected person. A mutation, delta 32, found almost exclusively in northern Europeans—and only in one percent of that population—shuts off CCR5, effectively closing HIV’s only door into the system. Hütter knew very little about AIDS research, but he postulated that if he could find a stem cell donor for Brown with the delta-32 mutation, he may be able to rid his patient of leukemia and HIV.
A relatively young doctor at 38, Hütter was not prominent at Charité Hospital, let alone among virus researchers. The idea was a long shot, one that no one had ever tried and that no one, not even Hütter’s colleagues, thought possible.
Brown again called his friend Elaine Fitch, now practicing law in Washington, DC, and explained the procedure. “But I don’t like the idea of being a guinea pig.”
“What do you have to lose?” Fitch said. “If this guy’s theory proves true, think what it could do not just for you but tons of other people.”
Brown paused, absorbing the words of one of his oldest friends.
“You’re going to get the treatment anyway,” she added, “so why not try it this guy’s way?”
Hütter’s way wasn’t easy. The doctor identified 232 suitable stem cell donors for Brown and paid $40 per sample to screen for the mutation. Only sample No. 61, from a German male, came up as delta 32.
The procedure Brown would undergo was a standard bone marrow stem cell transplantation developed in Seattle, Brown’s hometown, by Donnall Thomas, the cofounder of the Fred Hutchinson Cancer Research Center and a Nobel prize-winning researcher.
Brown stopped his antiretroviral regime and underwent the transplant in early 2007. He felt the difference overnight. “More energy and I was able to put on muscle weight. And I was looking better and feeling better,” he recalls. Tests showed zero trace of HIV in his system. Hütter’s wild idea appeared to have worked.
Before anyone could toast the victory, Brown relapsed. The leukemia returned a year after the treatment. “I thought he was going to die at that point,” says Fitch. “I took a trip out to Berlin because I thought I was going to be saying goodbye.”
A second transplant—again with No. 61’s stem cells—was a success. Brown regained his strength, and when he did he was whole and free of both HIV and leukemia.
There was another problem. No one believed it.
Hütter submitted a paper documenting the case to The New England Journal of Medicine, which swiftly rejected it. The claim was too outlandish. Thirty years of AIDS research hadn’t yielded anywhere near what a no-name German physician said he had done.
(Image: Courtesy Fred Hutchinson Cancer Resarch Center Fred Hutchinson’s Keith Jerome has studied HIV and other viruses since the mid-1990’s.)
Hütter settled for an explanatory poster at a Boston gathering of the Conference on Retroviruses and Opportunistic Infections in the winter of 2008. Again, few took the doctor seriously.
Dr. Jeffrey Laurence, an AIDS researcher at Cornell, did. He invited Hütter to speak about the so-called Berlin Patient to a group at MIT six months later. This time a journalist—a science writer at The Wall Street Journal—was present. The resulting article was read around the world.
The New England Journal of Medicine reconsidered Hütter’s claims. It published his original paper in the February 2009 issue, but with a caveat—an editorial in the same issue that threw doubt on the whole premise, penned by one of the original discoverers of the AIDS virus in the 1980s.
“It’s kind of surreal,” says Fitch. “I mean, to think that this scrawny little kid you grew up with is going to change the face of medicine because he was willing to work with this doctor who had this crazy theory. So now he doesn’t have leukemia and he doesn’t have HIV. It’s frankly astonishing.”
Keith Jerome agrees. “When the paper came out in The New England Journal, I said certainly there’s enough evidence here that something really amazing has happened,” he says. “Timothy Brown has been studied very carefully since by a tremendous number of highly qualified laboratories. It’s very clear that we’re not detecting the virus in his body now. So, I’m quite convinced at this point.”
But in addition to doubting Hütter’s claims—even Brown himself says he didn’t believe he was cured until he saw it published in The New England Journal—critics also pointed out the impracticality of the procedure.
Bone marrow transplants are almost prohibitively expensive—as much as $200,000 or more—and notoriously dangerous. Oncologists only recommend it as a last-minute, life-saving resort.
Was there a way to take the concept and adapt it in a way that was practical?
(Image: Courtesy Fred Hutchinson Cancer Research CenterHans-Peter-Kiem is adapting Brown’s HIV cure so that patients won’t need bone marrow stem cell donors.)
Proof that we are living in the age of miracles can be found at the laboratory of Dr. Hans-Peter Kiem on the campus of Fred Hutch. First a tall woman materializes in the lobby: short angular haircut favored by female leads in films set in the distant future; white sleeveless dress with horizontal blue lines at the hem, which hits just above the knee; a speed walk that leaves you four steps behind through a hallway crowded with lab equipment and into the office of Dr. Kiem.
Kiem sits behind a desk, the verdant campus framed in the window behind him. He favors blue buttonup shirts and a blue pen in the left breast pocket that may or may not be an intentional accent of color.
A German native, Kiem came to Seattle 21 years ago to follow in the steps of his hero, bone-marrow transplantation pioneer Donnall Thomas. Kiem admits that, like his Hutch colleague Keith Jerome, he was skeptical about Brown’s case at first. But he has read the papers, looked at the evidence, and is convinced the Berlin Patient is real. (Two other HIV-positive men in Boston have since undergone a similar marrow transplant treatment and now reportedly show no signs of the virus.)
Until Timothy Brown, Kiem says, cure was practically a verboten word in AIDS research circles. “Before we were talking about vaccines, prevention—which is all very, very important. But really nobody has talked about the cure. He’s launched an entirely new field.”
“Timothy has been wonderful about visiting with the AIDS researchers at our scientific conferences,” adds Jerome. “And he clearly has developed quite a sophisticated scientific mind, and so he’ll often ask questions.”
Kiem’s lab is at work developing a way to take the concept that cured Brown—trading good bone marrow stem cells for bad—but instead of using a donor, patients would receive their own reengineered blood and marrow stem cells; stem cells, Kiem hopes, that will be the equivalent of the delta-32 mutation, shutting the door on HIV so it can’t enter the immune system.
(Image: Josh Trujillo/Courtesy Fred Hutchinson Cancer Research CenterTimothy Brown meets with Fred Hutchinson researchers in June 2013.)
In just a few minutes, Timothy Brown will stand in front of more than 150 primary care providers, oncologists, and researchers—an auditorium so packed, dozens of attendees will sit on the floor just to glimpse the one true miracle many of them will ever see in the flesh.
But first, as if he somehow isn’t on the campus of the Fred Hutchinson Cancer Research Center, Brown lights a cigarette. An e-cigarette, mind you, its electric blue tip a pulsar that flares each time he brings the cigarette to his mouth. No smoke—just invisible hits of nicotine to put his bones at ease before he tells the story of how an anonymous expat in Germany became the most famous AIDS patient in history.
It’s June 18, 2013, and Kiem and Jerome have invited Brown and his new organization—the Timothy Ray Brown Foundation, the first organization solely dedicated to finding an AIDS cure—to the Hutch for a two-day symposium that will include a cocktail hour with the scientists and multiple talks by the researchers and Brown himself.
In the courtyard on campus, Brown takes a seat at an ornate metal picnic table in the shade of a maple tree. When he sits his charcoal blazer collapses outward in pillowy folds, so that, even at 47, he looks like a boy in a grown man’s suit. He takes another drag on his e-cigarette. Until 2010 he was known in the medical literature simply as “the Berlin Patient”; a German newspaper profile identified him as “Neil.” He came forward at last, he says, because he didn’t want to be the only person cured of AIDS. He was, in effect, tired of being a walking miracle who could not help others. Since then he has rubbed shoulders with the likes of Nancy Pelosi and Sharon Stone and spoken to crowds all over the country. (He now lives in a suburb of Las Vegas.)
Inside his body flows the secret that has escaped researchers since the virus was first discovered—the way to shut the door into the immune system, keeping out one of the worst plagues of our lifetime. Brown knows we have so far to go: Some 1.7 million people died worldwide from AIDS or AIDS-related complications in 2011.
He rises from the picnic table. His blazer falls flat against his lanky frame and he cuts across the courtyard. A pair of glass doors open then shut behind him. And Timothy Brown steps in front of the crowd to speak.
This article originally appeared in the December 2013 issue of Seattle Met.
The Face of the Cure
Timothy Brown once had HIV—but now he doesn’t. A small group of Bay Area activists and researchers are hoping to turn the breakthrough that saved him into a solution for the still-deadly plague.
ON A RECENT AFTERNOON, A THIN, BROWN-HAIRED MAN WALKS SLOWLY OUT THE DOOR OF THE AMBASSADOR Hotel in the Tenderloin and around the corner to the stop for the outbound Number 9 bus. His destination: the HIV/AIDS clinic at San Francisco General Hospital, one of the oldest such facilities in the country.
Known in the early days of the epidemic simply as Ward 86, the clinic was a place where physicians and nurses cared for mostly young patients who found their way there and died not long after. It’s now part of the new Positive Health Program, whose name reflects the seismic shift of the mid-’90s, when new drug combinations transformed HIV from a death sentence into a chronic disease. Today, patients who can’t afford private doctors go to the clinic for monitoring and treatment so they can live as normal a life as possible.
The man moves stiffly as he gets off the bus on Potrero Avenue and makes his way into the clinic. He is clean-shaven, with brown eyes, thinning hair, and a face that seems both young and old at the same time. He speaks softly, and when he smiles, he has a vulnerable look that suggests he’s been through an ordeal and been profoundly changed in the process. You’d never guess from glancing at him that he is different in a fundamental way from the other patients milling around, or that he is world-famous among scientists and patient advocates. But this 46-year-old man, Timothy Ray Brown, is the only person alive in the world who previously had HIV but is now completely free of the virus.
Just five years ago, Brown’s cells were riddled with HIV. But a daring experimental therapy banished it from his body. As such, he is living proof that one of history’s deadliest diseases—one that has killed some 30 million people and infected some 34 million more worldwide—can actually be cured.
For years, research aimed at curing AIDS was on the back burner—far, far back. Drug companies devoted their money to developing new treatment combinations—and government-funded research focused largely on prevention, which has been moderately successful, and vaccine development, which has been an expensive flop.
Brown’s story completely changes things up. “Timothy’s case has contributed in a major way to shifting the discussion about this disease—from managing it to trying to cure it,” says Steven Deeks, a veteran AIDS researcher and, for the past year, Timothy Brown’s physician.
So why haven’t we heard more about this remarkable development? Especially in San Francisco, which was ground zero in calling attention to the AIDS epidemic in the first place, you’d think Timothy Brown would be a household name.
But despite the near-miraculous nature of his cure, the world was very slow to learn about it—and him. Initially, he was known only as “the Berlin patient,” and the news of his cure didn’t spark the kind of excitement among researchers one would have expected. Partly it’s because Brown’s exact treatment wasn’t applicable to the typical HIV/AIDS patient. But a bit of professional snobbery may also have been in play. In a field of big names and long-established reputations, Brown’s doctor wasn’t well-known; in fact, he wasn’t even an AIDS specialist. He was an oncologist.
The story of how Brown’s case altered the landscape of AIDS research has many twists, but one that hasn’t been explored is the role that activists—many with deep roots in the Bay Area—played in bringing it to the attention of the health establishment. Many are veterans of the first wave of activism in the ’80s, which focused on prevention and disease management; this time they’re helping to channel significant money into cure research, much of which is now being conducted in and around San Francisco. In fact, a small biopharmaceutical company in Richmond has the best chance of coming up with a version of Brown’s treatment that could work for anyone with AIDS (assuming they’re not already too sick). If a cure is to be found, it will be due in no small part to the efforts of Bay Area scientists and activists.
THE MAN BEHIND THIS SEA OF CHANGE GREW UP IN SEATTLE, THE CHARISMATIC ONLY CHILD OF A SINGLE mother. As a teenager, Timothy Brown loved to read, talk politics, and party, remembers Elaine Fitch, a lifelong friend. He came out in high school and was the first gay person Fitch knew. “Looking back, it was an incredibly brave thing to do at that age,” says Fitch, now an attorney in Washington, D.C.
In the winter of 1990, Brown, Fitch, and another friend spent three months traveling across Europe, and Brown eventually settled in Berlin. “I wanted to enjoy my life and play,” he says. “I was concerned about getting infected with HIV, but not careful enough.” In 1995, he tested positive.
The next year, new drugs became available that suppressed the virus, letting him live without symptoms. Over the next decade or so, he studied political science and German, waited tables, and worked as a translator. But in the summer of 2006, things changed. Exhausted after a trip to New York for a wedding, Brown attributed his fatigue to jet lag. But then, back in Berlin, his usual bicycle ride to work also wore him out. He was soon diagnosed with anemia and given transfusions, but they didn’t help. He was sent for further tests, and a few days later, he had a diagnosis—acute myeloid leukemia, an aggressive blood cancer that is often fatal.
Almost immediately, Brown began a grueling series of treatments. At Charité University Hospital in Berlin, then 38-year-old oncologist Gero Hütter gave him around-the-clock chemotherapy for a week, then another round two weeks later. Midway through a third round, he became septic, his fever spiked, and he struggled to breathe, so his doctors induced a coma and put him on a respirator for 24 hours. He survived, and his leukemia went into remission, but it wouldn’t be Brown’s last brush with death.
Brown was told by doctors that if his leukemia returned (and he had the type that often does), he would need a bone marrow transplant to replace the cancer-ridden stem cells of his immune system with the cancer-free cells of a donor. Hütter had never treated anyone for HIV/AIDS before, but he had an audacious idea based on something he’d been mulling for a while.
HIV does its damage by attacking T cells, the workhorses of the immune system. But to get into T cells, it needs to use a protein called CCR5 that sits on the cells’ surface. In a small number of people, those with a genetic mutation called delta32, a piece of CCR5 is missing, making it nonfunctional. These people are resistant to HIV. Having one copy of the delta32 gene delays the development of AIDS by two to five years; having two copies makes people essentially impervious to HIV. Hütter broached his idea to Brown: If they did need to seek a stem cell donor, why not look for one with a double dose of the delta32 mutation?
At the time, Brown was focused on surviving leukemia and the ravages of chemotherapy—and wasn’t thrilled about the idea of being a guinea pig—so he didn’t jump at Hütter’s suggestion. But when the leukemia returned six months later, he agreed to give the treatment a try. Hütter searched a registry of bone marrow donors and found 232 whose tissue type matched Brown’s. Tests showed that Donor 61 (oddly enough, a German living in New York) had two copies of the delta32 gene. As the donor flew across the Atlantic to have his stem cells harvested, Brown lay in his Berlin hospital bed, worrying that the plane would crash.
The day before the transplant, Brown took his antiretroviral drugs for what would be the last time, and the next day Hütter infused Donor 61’s cells into his bloodstream. The transplant knocked out his leukemia—and by day 68, no evidence of HIV could be found either. The leukemia returned a few months later, though, so Donor 61 agreed to come back. After the second transplant, Brown spent four months in the hospital dealing with various complications and eventually moved to a rehabilitation center—but the prognosis wasn’t good. “Even Hütter didn’t think there was much hope,” Brown recalls. Fitch was worried, too, so she flew to Germany to see her friend for what she feared might be the last time. By the time she got there, though, Brown seemed to have turned the corner. “He was learning how to walk and use the bathroom and eat,” she recalls. “I was comforted that he wasn’t going to die.” Finally, in early 2009, nearly a year after the second transplant, Brown was able to leave the center. More troubles would lie ahead, but HIV and AIDS would not.
“IT WAS AN AMAZING FEELING – ONE I WILL NEVER HAVE AGAIN,” HüTTER SAYS ABOUT BROWN’S CURE. “I realized that this case might change the thinking about HIV in a revolutionary way.”
For a while it seemed as if that might not happen. Hütter had first described the case in a scientific poster tacked up at a Boston medical conference a year after the initial transplant. No media picked up on it, and none of the prominent scientists mentioned it in their talks. At least one took notice of it—Steven Deeks. “I saw the poster and thought it was fascinating,” he says. “I wondered, ‘Why is no one paying attention?’” But it was so early in the process that he pretty much forgot about it.
A whole year went by before Hütter got a bigger platform, describing the case in one of the world’s top health periodicals, the New England Journal of Medicine, in early 2009. At UCSF, Jay Levy, an AIDS researcher who codiscovered HIV, was asked to write an editorial to accompany Hütter’s paper. He took a cautious view, saying that the treatment wasn’t itself a cure but might lead to one that would mimic Brown’s treatment—without the need for a risky stem cell transplant. Since then, Levy’s enthusiasm has steadily grown. “It was an incredible development,” he said in a recent interview. “Before Timothy, very few people would have imagined that a person infected with HIV would suddenly have no more need for antiretroviral drugs.”
In fact, researchers at Sangamo BioSciences, a biopharmaceutical company near the Richmond Bridge, had been laying the groundwork for exactly the kind of treatment Levy envisioned. So when the news about Brown emerged, Sangamo chief executive officer Edward Lanphier says, it provided “a huge catalyst” to the company’s work. Sangamo soon gained investors and other funding and, together with partners at the City of Hope, a cancer research center near Los Angeles, and at the University of Southern California, the company submitted a joint funding proposal to the California Institute for Regenerative Medicine (CIRM), the state stem cell agency.
Sangamo’s innovative technology relies on something called a zinc finger nuclease (ZFN), a sort of programmable biological scissors that can snip out bits of genetic material at any point on a DNA sequence. The company is studying two ways of using it, each of which solves some of the problems inherent in Brown’s stem cell treatment.
In the first, some of the patient’s T cells, the immune cells that are attacked by HIV, will be taken from his blood and sent to the lab, where researchers will use ZFNs to slice out sections of CCR5, the protein that allows HIV to enter cells. The modified, HIV resistant cells will then be infused back into the patient. It’s a less invasive approach, but one drawback is that the modified T cells will eventually die out, so the patient’s ratio of modified to unmodified cells is likely to drop over time, necessitating further “booster” treatments to maintain the effect.
Sangamo’s second strategy aims for a oneshot fix by using ZFNs to alter not the T cells but the stem cells that form them. It will require a bone marrow transplant, but no donor: Patients will have their own stem cells removed and modified, then infused back into their bloodstream. Because such transplants are so risky, the first patients in Sangamo’s trials will have lymphoma, which may already necessitate the risky self-transplant.
The company is optimistic about its chances. “I think we’ll totally be able to cure HIV in a sophisticated first-world setting,” says Paula Cannon, an associate professor of molecular microbiology and immunology at USC. “It’s going to take time and money, and a big challenge is going to be how to apply the cure broadly so it’s not just an expensive boutique treatment but one that can be mass-produced.”
When Sangamo’s initial proposal came before a CIRM review committee, however, it encountered opposition, even though it got high scientific marks, says Jeff Sheehy, a veteran San Francisco AIDS activist and a patient representative on the CIRM governing board. “One reviewer said, ‘The science is great, but there’s no need because patients are doing great. They’re happy with antiretroviral drugs,’” recalls Sheehy, who is also communications director for UCSF’s AIDS Research Institute. “That’s when I said, ‘No.’”
Sheehy told the committee that today’s HIV drugs, which he’s been taking since 1997, are far from a total solution. At best, they turn HIV/AIDS into a chronic condition that requires lifetime therapy, at a cost of around $20,000 a year. The drugs can have significant side effects, including bone, kidney, and liver damage. People living with HIV are also more prone to cancer, heart disease, cognitive problems, and a host of other conditions. (A recent study suggests that having HIV may cut a person’s life expectancy by 13 years.)
“I lose friends every year to cancer or heart disease,” Sheehy told his audience. “That wouldn’t be happening if they weren’t infected.’’ As the father of a seven-year-old daughter, Sheehy worries that HIV might have the same effect on him.
His arguments won the day. In October 2009, CIRM awarded a $14.6 million grant to the City of Hope–USC–Sangamo team to develop its stem cell–based gene therapy. The researchers plan to begin trials within three years.
As Sheehy was making his case to CIRM, two other Bay Area activists were putting the Berlin patient, and the quest for a cure, on the radar of the general public. Kate Krauss lived in San Francisco in the early days of the epidemic and got involved with ACT UP, the in-your-face AIDS advocacy group that organized die-ins on Market Street. “When someone says I need to move some ossified bureaucracy, I don’t say it’s impossible,” Krauss says. “I’ve seen it.”
Krauss now lives in Philadelphia and directs a group called the AIDS Policy Project, part of whose purpose is to lobby for cure research. In November 2009, when Edward Zold, a comradein- arms from ACT UP, died of AIDS at age 38, Krauss came back to San Francisco for his memorial service, where she also hoped to garner more support for her work. The service was held in the National AIDS Memorial Grove in Golden Gate Park. She cried her way through it, but along with the tears, she was making her case. “I’d see some old activist friends and say, ‘Hi, nice to see you. I’m working on a new project on the cure,’” she recalls. “Then I’d go back to crying.”
For months, Krauss had been hearing astonishing reports about an anonymous Berlin man who’d been cured of HIV—and was thrilled that he might be, as she put it, “proof of concept.” During the week of Zold’s memorial, she stayed at the Oakland home of Stephen LeBlanc, another old friend and ACT UP veteran. The two strategized about how to mobilize for a cure.
Less than a month after Zold’s memorial service, Krauss wrote a column, “AIDS Cure Isn’t Out of Reach,” that ran in the Philadelphia Inquirer and on numerous websites. LeBlanc, meanwhile, reached out to San Francisco activists like Matt Sharp, a former ballet dancer who’d been living with HIV since 1988. In February of 2010, LeBlanc and Sharp organized a forum at San Francisco’s LGBT Community Center. At the meeting, scientists and advocates talked about the Berlin patient and the effort to develop drugs that could draw out and destroy pockets of HIV that linger, hidden, in the bodies of patients taking antiretrovirals. “The house was packed,” Sharp recalls. “There was a lot of excitement in the room.”
Four months later, the activists had a tangible milestone to celebrate: The National Institutes of Health (NIH), the largest funder of AIDS research in the world, announced it would begin funding projects that aim to eradicate HIV. The program, named for the late San Francisco AIDS activist Martin Delaney, had a budget of $8.5 million a year for five years. (When the awards were announced a year later, the amount had grown to $14 million a year.)
A month after that, Krauss’s AIDS Policy Project released a 25-page report, “AIDS Cure Research for Everyone,” that circulated widely at the International AIDS Conference in Vienna, the world’s biggest gathering of AIDS researchers and policy makers. Though federal investment in a cure was still paltry compared to the resources devoted to treatment, cure research had finally earned a place on the agenda.
Thanks in no small part to Brown, Fitch believes. “Tim fought harder than anyone could imagine possible,” she says. “If he had died, the world would have been robbed not only of a uniquely positive spirit but also of the possibility of a cure for all HIV-infected people.”
YES EVEN AS BROWN’S EXPERIENCE WAS HELPING TRANSFORM AIDS RESEARCH, HE WAS IN NO POSITION TO savor his singular good fortune. In October 2009, just months after being released from the rehab center, Brown was mugged on the streets of Berlin and left unconscious. He suffered a brain injury, spent four days in the hospital, and started the arduous task of rehabilitation all over again.
It took more than a year, but by the end of 2010, Brown’s health was restored and he was ready to tell his story. He did so first in the pages of Stern, a German newsweekly. Until then, Krauss and LeBlanc had refrained from trying to contact him out of respect for his privacy. But now that the Berlin patient had a name, Krauss located him on Facebook, scrolling through more than 100 Timothy Browns until she found the right one: a thin American who spoke German and English.
Just before Christmas, LeBlanc sent Brown a friend request, and Brown responded. It so happened that he had split up with his partner in Berlin and was planning to move back to San Francisco. “I thought I’d have support there,” he says. Brown arrived weeks later and moved, with LeBlanc’s assistance, to the Mission district and later to the Ambassador Hotel. LeBlanc suggested he make an appointment with Deeks, and accompanied him on his first visit. He also put him in touch with several AIDS activists.
“When I started working on this issue, everyone was afraid to say the C-word,” LeBlanc says. “The fact that a living, breathing person was cured directly countered those issues. He’s also a total sweetheart. I’m happy to be able to call him a friend.”
Although Brown is a bit of a celebrity—he’s been interviewed by George Stephanopoulos and Sanjay Gupta, he says with pride—his life here is largely a quiet one. For now, at least, the injuries from the mugging keep him from working. Finances are a challenge, although he has been able to earn some money from speaking at AIDS events in Toronto, New York, and the Netherlands, spreading the word that a cure is possible.
Brown has become part of two ongoing study cohorts at UCSF led by Deeks and Levy. Deeks has made Brown into something of a pincushion, taking multiple blood and tissue samples to check for evidence of the HIV virus and to track other changes. “He’s been very, very generous with his body,” he says. (Levy’s work is similar to what they’re doing at Sangamo.) In other research, Deeks and some UCSF colleagues, in collaboration with the Vaccine and Gene Therapy Institute of Florida, are looking for ways to eliminate dormant pockets of virus in HIV patients. And at San Francisco’s Gladstone Institutes, scientists are working with the University of North Carolina to uncover the molecular process that enables the virus to hide.
During Brown’s recent visit to Deeks’s fourth-floor office at the Positive Health Program, Deeks looked over test results and told Brown that his immune cells, out of balance since his transplant, were returning to a normal ratio. Brown, in turn, told Deeks about his recent visits to a physical therapist and a neurologist and about his troubles dealing with Social Security caseworkers. Brown is an unusual patient since he doesn’t have HIV, so Deeks helps him in other ways. He referred him to a brain injury clinic for therapy, and hospital social workers helped him get his room at the Ambassador.
I met Brown there one recent morning, and we talked in his small room. The space was cluttered but clean, with a double bed that serves as a couch and a radiator that he uses as a desk, his iPad and MacBook balanced precariously atop. Although his body has vanquished HIV, there’s a fragility about him. He moves and speaks slowly, sometimes pausing for a few seconds before answering. He doesn’t hesitate, though, when asked what brings meaning to his days now.
“My purpose is to try to effect a universal cure,” he says simply—an idea he expresses elegantly on his website: “My dream is not to be the man who stands before you and says, ‘I am cured,’ but to be the man who stands before you and says, ‘We are cured.’”
This article appeared in San Francisco Magazine, written by Rob Waters on May 21, 2012 it can be found here.