This Mysterious Billionaire Thinks He Can Cure HIV. Here’s Why.

Ragon, who is the sole owner of InterSystems and is worth an estimated $3.1 billion, believes — despite all evidence to the contrary — that we are on the verge of a similar scientific breakthrough in curing the estimated 39 million people worldwide living with HIV, the virus that causes AIDS.

It’s a little crazy. After all, massive organizations with far greater resources than the Ragon Institute have spent decades trying to develop an HIV vaccine. After years of trying and promising $500 million, Johnson & Johnson withdrew from the last major trial in 2023, a vaccine based in part on Ragon Institute research. In total, governments, nonprofits and companies have spent about $17 billion on HIV vaccine development over the past two decades, according to the nonprofit HIV AVAC. None have made it past phase 3 clinical trials. But Ragon is undeterred. He says government funders typically evaluate research proposals not only on their validity but also on the likelihood of the experiment succeeding. That’s never made sense to him. “You would expect most experiments to fail,” he says, which is why he believes his efforts, focused on funding riskier, earlier-stage research, will succeed where the bigger players have failed.

The need is enormous. HIV and AIDS have been largely contained in wealthy countries with expensive drugs, but the disease still killed about 630,000 people in 2022, mostly in sub-Saharan Africa and Southeast Asia. A U.N. study estimates that ending the epidemic could generate economic benefits of $33 billion a year in lower-income countries by 2030. The CDC says about 1.2 million Americans are HIV-positive; the lifetime cost of treating each person is about $420,000, according to a 2021 study.

Ragon’s approach involves bringing together scientists who don’t typically collaborate, including doctors, engineers, physicists, mathematicians, and virologists. The goal is to redesign people’s immune systems to cure them, which could have far-reaching implications for other diseases, such as tuberculosis, malaria, and cancer. “I’ve learned more from my failures than from my successes,” Ragon says. “And I think the same is true for science.”

Indeed, Ragon’s decades-long business success was the result of failure in another field: music. After graduating from MIT with a degree in physics in 1972, Ragon packed up his guitar and moved to London—his British rock heroes included Led Zeppelin, Jeff Beck, and Cream—to make it as a rock star. It didn’t work out. Returning to Boston, desperate to find a paying job, he noticed that job boards were filled with offers for computer programmers. After a few failed interviews, he was in the running for a position at Meditech, an early electronic medical records company. “I really don’t know much about computers,” Ragon recalls telling the interviewer, looking up to see a poster of Mick Jagger. “But I play guitar.” He got the job, which turned out to be an intensive course in an early programming language known as the Massachusetts General Hospital Utility Multi-Programming System, or MUMPS.

After a year and a half, Ragon left Meditech to co-found a medical billing company based on MUMPS. In 1978, he founded Interpretive Data Services, which he later renamed InterSystems. While other database companies like Oracle and SAP were offering companies a way to organize transactions into neat rows and columns, Ragon took a chance on a different type of database, coded in MUMPS and organized like tree branches connecting to central trunks. It was fast and reliable, and it was soon adopted by the Department of Veterans Affairs for medical records. InterSystems grew slowly: It took 24 years to reach $100 million in revenue—driven by its two largest customers, the VA and electronic health records company Epic Systems—and another 21 years to reach $1 billion by 2023.

Ragon remains optimistic that HIV will be cured in his lifetime, in part because he has taken a similarly methodical, long-term approach to building his software business. He draws inspiration from philosopher Thomas Kuhn, who famously argued that science progresses through long periods of slow evolution punctuated by radical revolutions that Kuhn called paradigm shifts. “Every once in a while,” Ragon says, “you get something that just turns the world upside down.”

His personal paradigm shift came during a hospital visit in South Africa at the invitation of Bruce Walker, an infectious disease researcher at Mass General and a professor at Harvard Medical School. It was 2007. InterSystems had just acquired an electronic health records company called TrakHealth, and Walker wanted to show Ragon the software in action. He recalls a frail young woman walking into a doctor’s office and the doctor pointing out a pulsing vein in her neck, indicating heart failure. “I’m sitting there watching her die,” Ragon says, overhearing the doctor ask if she believes in Jesus. “This would be a good time to schedule an appointment with my Maker,” he recalls the doctor saying before he discharged her. The United Nations estimates that 4,000 women between the ages of 15 and 24 are infected with HIV each week—3,100 of them in sub-Saharan Africa. Ragon knew he had to do something.

When HIV enters the body, it hijacks our cellular machinery to pump out new copies of the virus. Unlike Covid or measles, HIV inserts instructions directly into the DNA, meaning that the human host will be forced to make copies of the virus for as long as it lives. It is also “extremely variable,” says Daniel Kuritzkes, chief of infectious diseases at Brigham and Women’s Hospital in Boston, meaning that “each person has a virus that is slightly different from the next person’s virus.” The combination of these two properties makes developing an effective vaccine incredibly difficult.

To defeat one of nature’s most challenging viruses, Ragon Institute scientists are taking inspiration from an amazing and rare natural phenomenon: people who have HIV but have no symptoms and essentially can’t spread the virus. Known as “elite controllers,” their T cells are incredibly effective at attacking and killing the virus. Walker, who became the founding director of the Ragon Institute, first encountered the elite controller in the 1990s and has been trying to unlock the secrets of the immune systems of such patients ever since. “If we could get that state in people who are infected,” Walker says, we would have a “functional cure.”

Walker expects to begin phase 1 clinical trials in 2025 for a new T-cell vaccine that mimics a phenomenon in elite controllers in which the body attacks amino acids critical to the virus’s structure. Partners in the project include the Gates Foundation, the International AIDS Vaccine Initiative and Italian drugmaker ReiThera. Will it work? “We’ve been wrong before, and we may be wrong again,” Walker says.

Fifteen years ago, “about half the scientists said a vaccine was impossible,” Ragon says. Will there be a cure for HIV in his lifetime? He doesn’t waste a moment: “Yes.”

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