Gero Hütter’s paper begins: “A 40-year-old white man with newly diagnosed acute myeloid leukemia (FAB M4 sub-type, with normal cytogenetic features) presented to our hospital.” Yet behind the cold scientific facts lay a mosaic of human experience. Timothy’s journey didn’t stop when he was cured of HIV. He wasn’t the same person as when he first entered Charité hospital in 1995. He had gone through chemotherapy, a brain biopsy, ablative therapy, and a bone marrow transplant. It was enough to change anyone. Timothy walks with a slight limp and speaks slowly and softly. He occasionally gets confused, a side effect that will lessen as the years go by.
In 2011, Timothy moved to San Francisco. He was excited to return to his native country after spending the last decade in Germany. But things weren’t as easy in the States as they were in Europe. In Germany, Timothy received money from the government for his housing, food, and medical care. Everything was covered. This was important because, given Timothy’s condition, he couldn’t work and he still needed significant medical care.
Many people believe that because Timothy Brown is the Berlin patient, widely touted as the first person cured of HIV, he must make a decent living. This couldn’t be further from the truth. Timothy lives in a run-down government apartment building outside Chinatown. His neighborhood is not safe nor is his apartment building, whose residents frequently have problems with violence and drug abuse. His apartment is a single cramped room with just enough space for a twin bed and a hot plate. Unpacked boxes line the walls; there is no place for Timothy’s meager belongings. It’s difficult to keep pests out; his mattress is full of bed bugs. He has a tiny attached bathroom and access to a larger communal kitchen down the hall, which is too disgusting to discuss, much less cook in. In some ways, the apartment is barely his own; he is limited to the number of nights a week his guests can spend with him, limiting the amount of time he has with his boyfriend.
Timothy recently spoke with Marcus, the man who told him he needed to get tested for HIV eighteen years ago. As Timothy shared his story, how he was cured of HIV, he could sense Marcus recoil. “But who cares about curing HIV?” Marcus asked. Marcus had been on antiviral drugs for over a decade and couldn’t contemplate the millions of HIV-positive people who have trouble taking drugs or don’t have access to them. “You’re wasting your time,” he said to Timothy. Timothy was hurt by these words. Timothy’s hope was that by sharing his experience, an experience that was difficult, he would create enthusiasm for the long-awaited cure for HIV. To have a friend tell him that a cure wasn’t important wounded him.
Timothy is generous with his time, speaking at conferences in both the United States and Europe, usually without compensation. The audience has little idea that the man before them is barely able to pay his bills. Timothy is also generous with the donation of his blood and tissues, which he gives regularly to the lab of Steve Deeks at the University of California, San Francisco. Scientists regularly test his blood and rectal biopsy samples by ultrasensitive PCR for traces of the virus. Given that Timothy had traces of a CXCR4-utilizing virus, researchers believed the virus would rebound quickly in him. That’s because the donor cells Timothy received were naturally resistant to CCR5-utilizing viruses, not to CXCR4. All along, researchers had been warning Hütter that this would happen because CXCR4-utilizing viruses tend to pop up late in infection and cause rapid disease. The presence of CXCR4-utilizing virus in Timothy’s gut was a sure sign that the virus would grow and Timothy would have to restart his antiviral drugs.
Surprisingly, this did not happen. And no one knows why. Researchers postulate that perhaps CXCR4 viruses need some modification or weakening of the immune system from CCR5 viruses in order to grow. Although this doesn’t explain the rare cases in which individuals have been infected with CXCR4 and not CCR5. Some have postulated that perhaps the Δ32 mutation confers some resistance to CXCR4 viruses as well, altering some trafficking of the chemokine that we don’t understand. Probably the most logical answer is that there is some level of virus we can control. Although it’s difficult to quantify what the tipping point is, there’s a measure of virus we can live with without ill effect. This goes hand in hand with the experience of Christian, who also has a tiny amount of detectable virus in his resting T cells and lymph nodes. Despite this, he hasn’t had to take medication in fifteen years. Similar as well is the toddler who was declared functionally cured but has some detectable HIV in her resting T cells. Again, this is the real point. We may not be able to eliminate every trace of virus in a person, but we don’t have to. We simply need the right tools, be they gene therapy inspired by Timothy or early antiviral and eradication therapies inspired by Christian, to bring the virus down to a level we can deal with.
Steve Yukl, a colleague of Steve Deeks’s who works closely with him on Timothy’s case, made this fundamental point in 2012 at a small workshop on HIV in Sitges, Spain. Yukl had just announced some unusual results. He had sent out Timothy’s samples to multiple collaborators spread across the country to test for HIV. Using a highly sensitive PCR test for HIV RNA, they detected a low signal. The results, he cautioned, weren’t consistent, and because of how the assay was done, they weren’t reliable. In fact, he added at the conference, it was likely they had been contaminated. PCR takes advantage of the natural ability of DNA to bind and the power of the polymerase enzyme in order to produce infinite copies of a specific gene or other target. While PCR can be highly reliable, the more times it’s repeated on a single sample, the more unreliable it can get. This is because, by repeating the reaction multiple times, you use less and less of the original sample.
Timothy underwent numerous procedures and biopsies to give these samples to science. The samples are taken from his blood, rectum, ileum, lymph nodes. He even underwent a lumbar puncture to get a sample of his cerebrospinal fluid. The number of cells taken from each of these procedures is small, so the RNA amplified from them needs to be amplified an unusually high number of times. The more cycles of PCR done, the more likely a false positive. In an interview with Science, Douglas Richman, an HIV researcher at the University of California, San Diego, explained it this way: “If you do enough cycles of PCR, you can get a signal in water for pink elephants.”
Other problems in the analysis occurred. When different collaborators sequenced the virus they had amplified by PCR, it didn’t match the original virus Timothy was infected with. However, it also didn’t match among the collaborators. This was a sign of contamination. It was obvious that the results needed to be repeated since they brought up more questions than answers. Steve Yukl decided to share the preliminary results from Timothy’s samples as a means to discuss HIV reservoir with the group. Perhaps naively, he didn’t expect that the small group of scientists would be misled by the data. Why was this a big deal? Any sign that the Berlin patient might not actually be cured was sure to grab headlines. Although for those who were familiar with the case, it wasn’t news that Timothy might have virus hidden in his body. After all, in the original New England Journal of Medicine paper, Hütter discussed the traces of CXCR4-utilizing virus hidden in his gut. Technically, this wasn’t even news.
On June 11, 2012, a French HIV researcher who attended the meeting in Spain issued a press release with the headline THE SO CALLED HIV CURED “BERLIN” PATIENT STILL HAS DETECTABLE HIV IN HIS BODY. Contrast this headline with the title of Yukl’s talk at the meeting: “Challenges inherent in detecting HIV persistence during potentially curative interventions.” The press release mentions none of the caveats that Yukl made when presenting the now infamous data. It does not mention the strong possibility of contamination. Instead, it presents Yukl’s results as a “challenge” to Hütter’s cure data. Both Yukl and Deeks were perturbed when they saw how their data had been twisted in the media. In an interview with Science, Yukl sought to clear up the controversy, saying, “The point of the presentation was to raise the question of how do we define a cure and, at this level of detection, how do we know the signal is real?”
The press release reads, “These data also raise the possibility that the patient has been reinfected.” For Timothy, and others reading it, this suggestion was an insinuation about Timothy’s sex life, since the only logical way that Timothy could be reinfected is by having unsafe sex. The personal implication of the remarks made about Timothy reveals an inherent flaw in the relationship between scientist and research subject. Because our studies keep a distance between researcher and study subject, we lose our empathy. For Timothy the effect was humiliating. He watched as the popular press discussed his sex life and questioned his cure. Many HIV-positive individuals were also affected. Now confusion swirled around what these results meant and whether the Berlin patient was truly cured. It’s the kind of news that deteriorates hope in HIV-positive people who have suffered so many previous disappointments. It’s also the kind of news that shakes the public trust in science. Since that time, new data has shown that these preliminary results were false. In fact, when the tests were repeated no lab could find detectable virus. Yukl has said that Timothy’s treatment surpasses that of Bruce Walker’s HIV controllers: “Even the most extraordinary ‘elite’ controllers described in the literature have more robust evidence for persistent infection.” He has even gone a step further in saying that Timothy, while he is described as having a functional cure—that is, detectable virus in his body—“may even have had a sterilizing cure.” That is, no remaining virus at all.
This is not to say that scientists shouldn’t question the results they hear at conferences or that they shouldn’t openly discuss all the implications of new research. It’s important for researchers to do this, for it makes the community stronger. However, we need to consider the human factor when discussing research studies. Timothy is not simply the Berlin patient. In light of all he’s given research, he deserves our human respect.
• • •
Christian is in a very different place in his life compared to Timothy. Where Timothy’s life is tumultuous, Christian’s is stable. He says his life is relatively untouched by HIV. It’s the life dreamt of by many HIV-positive people waiting for a cure. Today, he has all he could have asked for at twenty-seven, when he was first infected with HIV. He hasn’t taken antiviral drugs in fifteen years. He has a job he loves. He travels the world on exotic vacations. He has a long-term partner whom he cares for deeply. Yet, his identity is muddled.
He considers himself HIV-positive, although he hasn’t harbored the virus in over a decade. He is not alone in this identity. Timothy, too, identifies himself as HIV-positive, although he’s cured of the disease. It’s almost as if the virus carries an identity of its own, and all those who have carried it, no matter how briefly, will have their lives forever changed by it. Being HIV-positive has become part of the Berlin patients’ characters, less a disease than a force that defines who they are.
Christian may identify himself as HIV-positive, but he has a harder time identifying himself as the Berlin patient. Given his mild personality, he dislikes connecting himself with the dramatic medical cure. For this reason his long-term partner, Greg, didn’t know he was the original Berlin patient until a year after their relationship started. Greg smiles when he describes the moment Christian first asked him to go with him to see Jessen. Greg was nervous; after all, what could Christian have to say to him that needed to be told at a doctor’s office? Was he sick? Imagine Greg’s surprise when he learned that Christian wasn’t sick or contagious. He was the original Berlin patient. Greg remembered the news coverage of the Berlin patient, the fantastic case of a man cured of HIV in Germany. He never would have expected that his boyfriend was at the center of such a dramatic medical story.
Christian and Greg have shared their lives for eight years. They spend holidays with each other’s families. They take wonderful vacations. They are the epitome of a happy couple, supported by their loving families. Christian remains in perfect health, having no lasting effects from his HIV infection. He thinks little about HIV research these days and doesn’t follow developments in the field. But hidden away in a drawer of his house lies a complex, handwritten schedule from 1996. It serves as a memento of the therapy he endured.
Timothy’s life is almost the reverse of this serene picture. His living situation is dreadful. His love life is tumultuous. His health is fragile as he suffers physically from the cumulative effects of his cancer and HIV therapy. Unlike Christian, Timothy is disabled and can’t work. Timothy is also committed to being part of bringing his HIV cure to others. In 2012, with support from the World AIDS Institute, Timothy launched the Timothy Ray Brown Foundation, a nonprofit dedicated to raising money for HIV cure research. It might seem an unusual move for a man with no money of his own. Timothy hopes that simply the power of his name and his story will bring attention to risky cure research in an era with shrinking funding for science.
Bruce Walker has found a way to combat the dwindling money for science. He has sought out private investors, angels in disguise, willing to put their money into risky research projects. This private funding, from donors like Mark and Lisa Schwartz, Terry and Susan Ragon, and Bill and Melinda Gates, is filling in the gaps. Without these sources, it’s hard to say what would happen to research projects with great promise but limited data. With this funding, Walker has built an entire institute on the shoulders (or rather the blood) of elite controllers. In the pipeline are new therapies and vaccines based on the personal genetics of those whose bodies control HIV.
Gero Hütter’s life has also changed in the years since he published his results on Timothy Brown. First ignored, then hyped, then adapted, Hütter’s research went on a roller coaster of influence. Given the scholarly articles published and the attention in the press, what happened next is surprising. Charité hospital shut down its transplant program. With funding problems shaking public hospitals and governments all over Europe, the Berlin hospital wasn’t immune to the budget cuts. The successful program, the first of its kind to cure a person of HIV, was slashed. While all those in the medical community assumed that Hütter would continue his work and find another HIV-positive person who needed a bone marrow transplant, he was, in fact, looking for a new job.
Today, Hütter is head of the Institute of Transfusion Medicine and Immunology at Heidelberg University in Mannheim. He has identified two other men with cases like Timothy’s who are HIV-positive but, because of their cancer, need a bone marrow transplant. He plans to use donors with the mutant Δ32 version of CCR5 in an effort to repeat Timothy’s success. He works with collaborators all over the world, including Sangamo. Although he’s the doctor who cured a man of HIV, his salary is modest. When he visits Berlin, he stays in a hostel. Hütter is married and has a son, born in the summer of 2012.
Heiko Jessen still runs his bustling practice in Berlin, working long hours and holidays. He loves his patients and treats them tenderly. He calls his young male patients his baby boys. He worries about them and takes their personal turmoil to heart. He sees his patients as part of his family. His own family is precious to him. He is close to both his brother, a fellow physician in the practice, and his sister, an infectious disease nurse. His parents, who are enormously proud of their son, visit several times a year. His sister’s preteen daughter, Mala, a beautiful, vibrant young girl, is like a daughter to Jessen. He spends much of his time with her. What Jessen does not have is a partner to share his life with. No one has yet compared to Andrew, the one who got away, the inspiration behind the Berlin patient. Jessen fills the void with close friends, his medical practice, and his family.
On a warm summer night in Berlin, I sit with Jessen on a rooftop terrace overlooking the city. He asks, “Do you think I should look at hydroxyurea again? Should I revisit the patients I gave it to?”
I nod my head. “You never know what you’ll find.”
The capital spreads out beneath us, a glittering masterpiece of contrasting architecture, on one side the stark modern buildings of the East, on the other the historic, ornate buildings of the West. The world of HIV once seemed as hopeless as the healing of Europe’s twentieth-century wounds. But that night the cure seemed to sit peacefully in each of our laps. . . . Patients keep fighting their personal battles; researchers keep fighting their institutional battles; doctors keep trying to bring the two groups together for their mutual benefit. And for all of us.