In 2008, Timothy was coming back to life. When everyone was sure he would die—his doctors, friends, and family—he began to recover. He turned from a “vegetable” that lay in bed all day to a man who wanted to go for long walks. After the doctors repaired the torn membrane in his brain, he slowly returned to moderate activity. In a matter of weeks, he went from certain death to a rehab clinic. He kept to himself in the clinic, making no friends. Instead, he wandered around the hospital with his vision blurry and his legs weak. He found an Italian restaurant nearby that he liked, often eating there alone. Pieces of his normal life were coming back. Lucas, deeply relieved by his recovery, visited him, his new boyfriend in tow.
Life was moving on in a way. Timothy’s memory was limited and his brain foggy. He had no job nor prospect of one. He felt lucky to be in Germany, where 26.7 percent of the gross domestic product is channeled back into the public welfare system; it’s one of the most comprehensive welfare systems in the world. Compare this to the United States, which channels 15.9 percent of the GDP into welfare programs. Timothy relied on the small monthly stipend and free medical care he received from the German government to survive.
Hütter prepared to show other scientists Timothy’s data. For the past year, since his first transplant, Hütter had organized a team of collaborators, all intent on analyzing Timothy’s cells. In a show of solidarity, departments from all over the hospital donated their time and resources to this one-of-a-kind patient. They sequenced the virus hidden in his cells and measured the HIV-specific antibodies Timothy’s body was making.
During this tense year, Hütter was inching closer to his hopes for Timothy. Each appointment brought the same news; the virus was undetectable and the CD4 T cells were steadily climbing. It was remarkable. However, the road still had some bumps. One of Hütter’s biggest scares came five months after the first transplant, when a rectal biopsy was performed on Timothy. In the pinches of cells the biopsy had collected were CCR5-expressing macrophages. These findings were in direct contrast to what they found in the blood, where 100 percent of Timothy’s cells were CCR5-negative and resistant to HIV. This was a bad sign. It meant that the strategy hadn’t worked; they hadn’t been able to replace all of Timothy’s normal CCR5-expressing cells with the Δ32 mutant version the HIV-resistant donor had provided. Worst of all, these cells were located in the gut, HIV’s breeding ground. Hütter was, again, unnerved. Oddly enough, the CD4 T cells in the same biopsy pinches were CCR5-negative.
He was about to get even worse news. Ultra-deep sequencing of Timothy’s gut revealed the presence of viruses that use CXCR4. Here was a disaster. The infectious disease specialists had told him this would happen. HIV would sneak around his lock on CCR5 and use a different receptor, CXCR4, instead. He waited patiently, fully expecting the CXCR4 virus to take over, even stronger than the original virus.
Though Hütter waited, the virus didn’t come back. Neither did the new CXCR4-using virus take over. It didn’t make sense. Was it possible Timothy was able to control the virus on his own? The cells in the rest of Timothy’s body remained CCR5-negative, the virus was undetectable, and the CD4 T cells, which were close to zero in the days before the first stem cell transplant, were flourishing. They had slowly climbed to the normal, healthy levels of a person who has never had HIV. No doubt about it, Timothy was controlling what had once been decades of an insidious viral infection. Hütter’s risky, unconventional experiment had worked.
He first presented the data at a small hematologist meeting. His data received no response. Hütter wasn’t surprised. He had been expecting this. He knew hematologists like himself wouldn’t be interested in Timothy’s case. He had to bring the data to infectious disease doctors and HIV researchers. They, he knew, would not take his data so lightly. Excited, he applied for a talk at the Conference on Retroviruses and Opportunistic Infections, or CROI, one of the biggest meetings for HIV researchers. He knew his unique patient would capture the attention of those interested in new therapies.
At the same time, Hütter decided to write up his findings. He put together the data and wrote the manuscript. Just as with Jessen’s paper, a major battle over authorship ensued. Eckhard Thiel, the chief of transplantation medicine, although coming into the study late, took the senior-author position. He replaced Wolf Hofmann, originally considered the senior author. As compensation, the paper states “Drs. Hofmann and Thiel contributed equally to this article.” The battle didn’t end there. It was the first time the hospital would have a paper in The New England Journal of Medicine, and the power of being published in such a prestigious journal made everyone act a little nutty. All over the hospital, physicians were coming out of the woodwork, asking to be included on the paper. One physician who disliked Hütter challenged his first-authorship. This colleague even threatened to remove his name from the manuscript when he didn’t get his way.
In the midst of this insanity, Hütter submitted the paper. It was an exciting period since it was the first time he had ever written a research paper. Not only was it his work, which he was immensely proud of, but he was submitting it to the top journal in his field. His excitement grew when he got the reviewer comments back. Scientific articles pass the first stage of acceptance when they are sent out for peer review. The article is sent to other experts in the field who anonymously cite the strengths and weaknesses of the paper and either recommend or reject it for publication in the journal. Though the reviewers exert significant interest, the decision ultimately rests with the journal’s editor.
Although he didn’t know it, Hütter was entering this process handicapped. One of the reasons Jessen’s paper on the first Berlin patient was accepted so quickly was because of his collaborators. Reviewers like to see names they recognize; it helps them trust the data they are evaluating. Hütter, with no prior record in HIV, and no collaborators in the field, was an anomaly. What’s more, his data were provocative. There had never been a documented case like it. Speaking to the strength of the data, the reviewer comments were positive. The editor, however, was unimpressed. Hütter had no background in HIV research. He couldn’t publish an article from an unknown entity; it was taking too much of a risk for the journal.
Hütter decided to resubmit his manuscript as a letter. This would mitigate the risk for the journal, for the responsibility for the contents of letters rests on that of the sender, not the publisher. In science journals, letters are not simply quickly jotted pieces of correspondence. They are highly crafted, peer-reviewed articles in their own right, and they carry significant prestige. Much to Hütter’s dismay, the editor rejected his letter.
As this was happening, he learned from the organizers of CROI that he would not be awarded a talk. Instead, he would be allowed to present a poster of his data. Here was another blow. Poster sessions at CROI, while still valuable, are not nearly as prestigious as a talk. It showed how little the HIV community thought of Timothy’s case. Hütter simply couldn’t understand it. Here he had proof that a stem cell transplant from an HIV-resistant donor was able to turn the cells in Timothy’s body into a lean, mean CCR5-negative machine able to keep HIV at bay. He had transformed Timothy from an HIV-positive person who took HIV medicine for a decade into a man who hadn’t taken antiviral drugs in more than a year. How could the HIV community not be excited about this?
He traveled to Boston in 2008 for the CROI, carrying his poster entitled “Treatment of HIV-1 Infection by Allogeneic CCR5-Δ32/Δ32 Stem Cell Transplantation: A Promising Approach.” His wording was careful; nowhere did he mention the word cure. Instead, he suggested that these results presented a therapeutic option for HIV-positive patients. It was a snowy afternoon in Boston as Hütter stood by his poster in the large conference hall. Right next to his poster was one from Bruce Walker and his collaborators in New York. Their poster, which was on reprogramming storm trooper T cells to make them HIV-specific, won a poster prize. Crowds gathered around the poster, full of eager, excited questions. Hütter’s poster, on the other hand, remained quiet. It seemed no one was interested in his patient.
Just when it seemed his experience at the conference couldn’t sink lower, Hütter attended a talk with some worrisome implications for his study. During the conference, trial results were released for a new drug: maraviroc. Maraviroc is designed to mimic the action of the Δ32 mutation. It sits protectively on top of the T cell, blocking HIV from using CCR5 to enter the cell. It is a similar philosophy, although a different approach, to Hütter’s stem cell transplant. This particular study, because it looked at a skewed patient population, had some disappointing results. Hütter was stunned to learn that in 64 percent of HIV patients taking maraviroc, HIV switched from the common CCR5-using virus to a more aggressive virus that uses a different receptor: CXCR4. This was dangerous. Viruses that use CXCR4 cause a person to accelerate to AIDS faster. Hütter fretted over the implications for Timothy. Even if he succeeded in making Timothy resistant to the HIV he harbored, it seemed the virus would find another way.
Hütter’s heart was heavy as he returned to Germany. Timothy might be dying in Berlin. The HIV community wasn’t taking his research seriously. He couldn’t publish his results. He was returning to a bitter hospital environment. In his hands, he held data proving that he had effectively cured a man of HIV. But he didn’t know it yet. The future was bleak.