It was a disingenuous dismissal: New treatments often start out dangerous, inconvenient, and expensive. It is only with additional research that they gradually morph into, say, a one-pill-a-day therapy that can be administered anywhere, as anti-retrovirals now are. “Picture Alexander Fleming with his vats of penicillin,” says Cannon, “and people saying, ‘Oh, yeah, that’s totally going to work in sub-Saharan Africa.’ ”
Among the big questions remaining about gene therapy is whether all relevant receptors need to be disabled to achieve full HIV resistance. CCR5 is by far the most important of those receptors, but it isn’t the only one, and we don’t yet know how significant this is. With Brown, it didn’t seem to matter. This could be because he had ablation—his immune system was wiped out by chemotherapy and radiation before his transplants. But that raises another puzzle: Could ablation itself be a necessary ingredient to a cure? Full ablation is a punishing experience, and even partial ablation requires hospitalization. No cure is practical on a wide scale if it must employ it.
Science, of course, has ways to find out. Building on Cannon’s work, a clinical trial in San Francisco and Philadelphia is testing whether using the genetic scissors not on stem cells but on T-cells—immune-system cells—to modify them with the CCR5 mutation can also yield HIV resistance. The use of T-cells has some disadvantages, but its big plus is that the procedure wouldn’t require ablation. “If that virus moves, it’s kind of a new universe,” says Jay Lalezari of Quest Clinical Research, one of the trial’s leaders.
Gene therapy is only one possible path to an AIDS cure, and the fact is, it may not be the best one. There is also a less flashy approach, one explored before cure acquired its air quotes: eradication, in which a patient on anti-retrovirals is given an additional drug that wakes up the latent virus so that it can be eliminated. Scientists have identified several different substances that can turn the virus on or off, but so far, none has worked safely in people.
Answers may be years away, but until recently, nobody was even asking the questions. They’re asking now—the International AIDS Society has just set up a working group on an AIDS cure. Despite the early doubters, “the Berlin Patient proved to be a tectonic shift in the way the scientific community looked at this issue,” says AMFAR’s Frost. “I’ve lived it—we started to talk about it internally, then in public. I got e-mails from prominent scientists warning me I was raising false hope. It wasn’t until there was a scientific consensus that the Berlin Patient was cured that people came around.”
If a cure for AIDS is no longer “the C-word,” it’s not yet clear that sufficient money will follow the renewed sense of hope. Gene-therapy research has been almost entirely financed by two new entities: One is Sangamo; the other is the California Institute for Regenerative Medicine, or CIRM, which since 2007 has given out more than $40 million in grants for AIDS-cure research, including $14.5 million to Cannon.
While the pharmaceutical industry has sunk hundreds of millions of dollars into developing AIDS treatments, most drug companies are sitting out cure research. (One big exception is Merck, which is funding studies of some of its drugs’ possible uses in eradication; Gilead is also looking at its compounds for cure candidates.) It’s no mystery why. “The whole field suffers from the lack of a business model,” says Jeff Sheehy, a San Francisco activist and CIRM board member. “A cure may make sense from a public-policy point of view, but not to a company.” Unlike treatment, which must be taken daily for life, a cure would be a one-time intervention. “It’s not that it’s sinister and they don’t want a cure. But it doesn’t fit.”
Drugmakers’ indifference can doom promising potential cures, as compounds owned by a company can’t be used by anyone else. Many AIDS researchers are particularly excited about the eradication possibilities of a substance developed by Medarex. But Medarex was bought in 2009 by Bristol-Myers Squibb, which is testing the compound on cancer but doing nothing visible with it on HIV. (A spokeswoman says the company is “considering the use” of the drug in HIV research, but no trials are set.)
Nor has the NIH’s National Institute of Allergy and Infectious Diseases, the world’s largest funder of AIDS research, made a priority of cure research. According to its own figures—as obtained and published by Krauss—the NIAID spent $40 million on cure research in 2009. That’s 3 percent of its total AIDS-research budget. (Fauci argues that this doesn’t take into account other research that may eventually apply to a cure.) Until recently, the NIAID did not even have an internal code for AIDS-cure work.