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The first reaction when you hear Timothy Brown's story is disbelief. For such a historic figure, he is remarkably anonymous.
Brown is known to scientists as "The Berlin Patient," the only human known to have been cured of HIV/AIDS. Brown, who lives in San Francisco, carried the virus for more than 10 years until it essentially disappeared with an experimental treatment in 2007. Ever since, scientists from around the world who have tested him have yet to find any sign of HIV infection in his system.
So Brown may not be well known to the public, but "he's a rock star to scientists," said Paula Cannon, a microbiologist at USC. "We appreciate what he represents, but it's also because he was able to come out and say, 'I was that person.' "
Brown's apparent cure came from a blood transfusion involving a donor who had a rare mutation of a single gene found almost exclusively among northern Europeans. The mutated gene, believed to be traced to the Black Death, can prevent the human immunodeficiency virus, or HIV, from infecting a cell.
Today, Cannon is working with a team of scientists to duplicate the cure with funding from the $3 billion stem cell bond passed by California voters in 2004. It's going well. It has proved to be safe and to eliminate HIV in humanized mice. And in coming months, scientists hope it will receive federal approval to begin human trials.
"Basically, this will give hope to the rest of the world," Brown told me in an interview. "I believe what I went through was actually good because it's led to a lot more research. It's shown a case in point that HIV can be cured."
The possibility of curing a global pandemic like AIDS with funding from the California bond is exactly the kind of exciting potential that inspired voters to approve Proposition 71 by a wide margin. But the HIV research is also a good example of the challenge facing the state's stem cell agency as it tries to show voters that they made a good investment.
None of the research under way will reach patients until long after the 10 years of funding by the ballot measure runs out. With the HIV project, researchers hope to be in human trials by 2014, but it is likely to be at least 10 years before they can show it might work in humans. And in the case of a stem cell cure for AIDS, it would be many years after that before a treatment is widely available.
That's partly due to the caution of dealing with new and powerful techniques, and the reality that each scientific step takes time to assess. Even with rapid scientific advance, it also shows how much is still unknown.
Nobody thought stem cells might be used to cure HIV when the bond passed. Far from the embryonic stem cell treatments that inspired the ballot measure, the HIV research involves a new and growing integration of stem cell and genetic science.
Scientists have known since the early 1990s that the rare mutation of a single gene called CCR5 can protect against HIV infection. Brown was the test to see if it would work in somebody who did not have a natural mutation.
Brown required a blood transfusion to treat leukemia, which he developed more than 10 years after he was diagnosed with HIV. And he was fortunate to be living in Berlin at the time. His doctor, Gero Hutter, was aware of the CCR5 mutation and invited Brown to participate in an experimental transfusion aimed at both the leukemia and the HIV.
It worked. But it also took several more years for scientists to accept that Brown had actually been cured. Today, they're still working to determine whether he has a "sterile cure," where all of the virus is eliminated, or a "functional cure," where harmless traces remain.
Cannon is part of a team that is developing a genetic treatment to essentially duplicate the northern European mutation by shutting off the CCR5 gene. The treatment involves a technique developed by Sangamo BioSciences in Richmond, a collaborator with Cannon and the City of Hope in Los Angeles, beneficiaries of $14 million in state stem cell funding.
The technique, called the zinc finger nuclease, involves a molecular scissors that was discovered years ago as a defense mechanism used by some bacteria. Scientists can attach a set of biological instructions so that the scissors will enter a cell and snip the DNA precisely at the location of the CCR5 gene. When the DNA reproduces an exact copy of itself, it includes a non-functioning CCR5 gene.
Blood stem cells are then used to spread the modified DNA throughout the body. Scientists have known for decades that stem cells in the blood and skin regenerate for long periods of time so skin and blood are constantly replaced. Unlike embryonic stem cells, which can grow into any cell type, the blood and skin stem cells reproduce only themselves.
The human trials that scientists hope to begin by 2014 will be limited to lymphoma patients who also have HIV. Lymphoma patients require a blood transfusion, and scientists plan to introduce the treatment during that process.
Even if it works, the transfusion is considered too traumatic and risky to treat patients who already manage their HIV with drugs. But if it's successful, scientists hope someday to deliver the treatment in other ways, perhaps with a vaccine that would work like a virus, tracking down cells in the immune system and penetrating them with a zinc finger nuclease.
"It is something that we will be able to do," Cannon said. "I want to be able to transport this thing down to South Africa," where the vast majority of those infected with HIV are living.
Jeff Sheehy, a prominent AIDS activist and a board member at the stem cell agency, called it "the global home run. That's not in 10 years. But this could be the beginning of something really amazing."
Cannon's confidence is not based solely on the potential HIV cure. The ability to modify genes and to deliver the treatment with a virus-like vaccine is a technique that can be used for many hereditary conditions. "This is really the holy grail of gene therapy," she said.
Several other approaches to cure HIV also are under way. And while the stem cell approach has received considerable attention among scientists and AIDS activists, it's still unclear which technique will prove most effective.
It's an exciting time for scientists who considered AIDS incurable just a couple of years ago. But for patients and the public, the excitement is tempered by the years of research ahead.
That's also a challenge for the state's stem cell agency, known as the California Institute for Regenerative Medicine. In a report adopted last month, it set ambitious goals for the five years left in its funding even as it described the lengthy time frame.
"As CIRM seeks to bring discoveries from the laboratory to new treatments it does so with the knowledge that the cycle of discovery to translation often takes decades," the report said. "CIRM is working diligently to rapidly accelerate this process, but it is important to understand that the full fruition of CIRM's investments to date will likely take many years."
The high cost of research and the distant payoff is also a deterrent for other funding sources. So among the biggest unknowns in stem cell science, one is about how it will be sustained at a time of shrinking government budgets.
"I know what needs to be done next," Cannon said. "But it's incredibly high risk, and I think it will take a long time and quite a bit of money. But it's incredibly worth doing."