The Conference on Retroviruses and Opportunistic Infections had been a difficult journey for Hütter as he struggled to establish himself as a researcher in the HIV community. Although his poster wasn’t widely attended, he made some critical connections that would carry him on the path to publication. He met Steve Deeks, a physician and HIV researcher at the University of California, San Francisco, and Jeffrey Laurence, director of the Laboratory for AIDS Virus Research at Weill Cornell Medical College. Laurence, talking about Hütter’s poster at the conference, said, “I thought it was the most exciting thing I’d heard about since the discovery of the virus. I couldn’t believe people didn’t take notice.” Enticed by his work, Deeks and Laurence invited Hütter to a “think tank” sponsored by the Foundation for AIDS Research, or amFAR, later that year.
Returning to Boston in September, Hütter had a very different experience. He was no longer standing quietly next to an ignored poster in a crowded conference hall. He was now able to present his data to the HIV researchers in the community who could best appreciate it. The think tank discussed CCR5, reservoirs, eradication strategies, and viral latency. In 2008, it was a field that was blossoming, with new data pouring in from labs all over the world.
In the think tank, data were presented from John Zaia, a researcher at City of Hope hospital in Duarte, California. Zaia was pursuing a high-risk strategy in a small group of patients who had the same kind of cancer as Timothy: acute myeloid leukemia, or AML. Zaia was interested in a gene therapy approach to treating HIV. He was looking at no fewer than three different methods to knock out the CCR5 gene that HIV needs to enter human T cells. The first method built on work that Lisziewicz had done nearly two decades earlier during her time in the Gallo lab. Zaia used small pieces of HIV RNA, called short hairpin RNA, capable of binding to the virus as it tried to reproduce itself in a cell, so that the virus couldn’t make more of itself. His gene therapy also included a decoy molecule, called a TAR decoy, to which HIV mistakenly binds when trying to insert itself into human DNA. Finally, Zaia’s ambitious project also included a ribozyme, which is a uniquely structured RNA molecule that has an effect like an enzyme. The ribozyme he included was able to bind CCR5 on the body’s cells, rearranging the atoms of the gene and blocking them from HIV’s grasp.
He delivered these three very different gene therapy components using HIV itself, or at least a version of the virus crafted to be innocuous. The way most gene therapy works is that a virus takes genetic material into the body and circulates it. It might sound scary, but we can create viruses that are not harmful in themselves and, if they carry the right genes, can be extremely beneficial.
Zaia was testing this highly experimental gene therapy in patients who had both AML and HIV, just like Timothy. This patient population was ideal for his study, for they needed to undergo the dangerous conditioning regimens necessary to receive hematopoietic stem cell transplants. Adding the gene therapy seemed like a small risk in comparison. There was another reason this was an ideal population on which to test a gene therapy: It was a patient population with a high mortality rate, making it a group of people more likely to take big risks. Just as HIV patients in the late 1980s were desperate for any clinical trial, today AML patients with HIV have a high mortality rate and are in desperate need of new interventions. Physicians and researchers are likewise torn about protecting the safety of their patients versus giving them a chance at survival.
When John Zaia heard about Hütter’s patient, he was stunned. Here was the proof that his strategy could actually work. Even though their methods were worlds apart, they were both targeting the same goal: Take down CCR5 to take down HIV. Zaia knew that the existence of a patient such as Hütter described was exactly the “proof of principle” that the HIV gene therapy field needed to take his study seriously.
Just as Jessen couldn’t have published the data from his Berlin patient without the backing of those hard-hitting HIV researchers who reviewed and bolstered his data, Hütter couldn’t get published without the help of the same major players in the HIV world. At the top of the list was Bob Siliciano, the same researcher who used his ultrasensitive HIV test to measure virus in resting T cells from the first Berlin patient; he now turned his sophisticated techniques to Hütter’s patient. Once again, vials of cells and blood sera were being shipped from one patient in Berlin all over the world.
At the think tank, Hütter also met Mark Schoofs, a Pulitzer Prize–winning journalist. Considering Schoofs was a journalist and not a scientist, he would have a surprisingly important role in Hütter’s finally getting his paper published. In 1998, exactly ten years earlier, Schoofs had interviewed Heiko Jessen, Bruce Walker, and other key scientists on the first Berlin patient for The New York Times Magazine. He had conducted the first of the only two interviews with journalists that Christian would ever submit to. Schoofs had played a key role in the subsequent media storm over the first Berlin patient. Now, here he was talking to Hütter, about to break the story of the second Berlin patient. Schoofs wrote up the story in November 2008 for The Wall Street Journal in an article entitled “A Doctor, a Mutation and a Potential Cure for AIDS.” When Hütter read the article, complete with his picture, he worried. Like Jessen before him, he hated seeing the “c-word,” cure, in the headline. He also worried that he had stepped over a line. To go to the press before publishing in an academic journal is a scientific sin. Those who fall prey to the lure of media attention usually pay for it with rejection from prominent journals. Hütter still hoped to be published in The New England Journal of Medicine. Had he dashed his chances?
Data began to roll in from Hütter’s new collaborators. Siliciano hadn’t been able to find any traces of virus, and neither had his other collaborators. The verdict was unanimous: Timothy had a functional cure. When Hütter told Timothy, he was unimpressed. “But what about the cancer?” he asked. Being cured of HIV was beside the point for Timothy.
Hütter revised his paper based on what he learned at the think tank and through the help of his new collaborators. However, the data in the paper didn’t change. Hütter resubmitted his paper to The New England Journal of Medicine, this time, thankfully, getting a new editor and reviewers. He waded his way through thirty pages of reviewer comments, a process that was new and overwhelming to him. The reviewers nitpicked every piece of his data, sometimes, it seemed, willfully misunderstanding him. Despite the torture, Hütter answered all the reviewer comments himself.
The article Mark Schoofs wrote had the opposite effect than anticipated. Instead of making Hütter’s actions seem self-aggrandizing, the article leant Hütter legitimacy in the eyes of the prestigious journal. His article was accepted and then published on February 12, 2009. The article itself, “Long-term Control of HIV by CCR5 Delta32/Delta32 Stem-Cell Transplantation,” was a spectacular achievement. The Berlin patient who had been whispered about for almost a year in the HIV community was finally in print.
Hütter’s paper begins: “A forty-year-old white man with newly diagnosed acute myeloid leukemia (FAB M4 sub-type, with normal cytogenetic features) presented to our hospital.” Behind the clinical description stood a frightened man. Timothy, in the wake of the publication and subsequent publicity, didn’t believe he was cured. He worried about his identity becoming known. He hated the idea of getting attention for his “cure” only to have the virus return. Timothy had been HIV-free for only two years, two very difficult years. A quiet, reserved person, Timothy couldn’t imagine ever giving up his anonymity.