As the founder and sole owner of software company InterSystems, Phillip “Terry” Ragon is worth about $3.1 billion, according to Forbes. Now, he is applying his successful long-term approach to business toward a new challenge: curing HIV.

Ragon and his wife, Susan, have donated about $400 million to HIV cure research. What makes the billionaire businessman think his Ragon Institute in Cambridge, Massachusetts, will see more success than HIV researchers across the globe have experienced during the past four decades? (To date, no HIV vaccine has made it beyond Phase III trials, and a cure has been elusive.)

Ragon is funding riskier, earlier-stage research, he tells Forbes, instead of putting the money in projects deemed not only important but also more likely to succeed.

“We started to evolve this whole idea of a Manhattan Project on HIV,” Ragon said, making a reference to the program that helped build the first atomic bomb during World War II. “If you tried to do the Manhattan Project back during World War I, you would have failed because we didn’t know about quantum mechanics. If you waited until World War III, you’d have been too late.”

He believes that scientific progress sees long periods of slow growth and then experiences a paradigm shift. We are due for such a game-changing advance in the world of HIV cure research, and to spur it along, Ragon is bringing together scientists, mathematicians and other experts who don’t usually collaborate.

The HIV cure research team at the Ragon Institute is inspired by “elite controllers,” folks who are living with HIV but show no symptoms of illness despite not taking HIV meds; in fact, they control the virus naturally and don’t have a detectable viral load. To read a POZ cover story on one such elite controller, Loreen Willenberg, see “An Exception to the Rule.” Willenberg may be the first person considered cured of HIV without having a stem cell transplant. (The handful of people who have been cured so far have undergone stem cell transplants to treat their leukemia. For a recent example, see the POZ interview with Paul Edmonds, “Sharing the Hope.”)

Bruce Walker, the founding director of the Ragon Institute, says researchers are trying to replicate the powerful immune systems of elite controllers. “If we could achieve that state in people who are infected,” Walker tells Forbes, the results could lead to a “functional cure.”

For this HIV cure project, Ragon scientists have teamed up with researchers at the Gates Foundation, the International AIDS Vaccine Initiative and the Italian drug developer ReiThera, according to Forbes. Next year, they plan to start Phase I clinical trials of a T-cell–based vaccine that they hope will replicate the immune system of elite controllers.

Despite a losing track record, the quest for an HIV vaccine and cure continues on many fronts. To read a collection of POZ articles on the topic, click #Cure. You’ll find headlines including: