George Painter, PhD, is the chief executive officer of DRIVE, a not-for-profit company wholly owned by Emory University but with the independence to run like a biotechnology company. He recalls his career and its intersection with the innovations in Dennis Liotta’s lab, where critical HIV antiretroviral drugs were created.
Meeting Dennis Liotta: Dennis came to Emory in 1976. I was a senior graduate student, and he was a young assistant professor, so he was here (at Emory) all hours of the day and night as was I, so we became acquainted. But really, the reason I kept coming and going from Dennis’s lab was his first student. There was a woman working in his lab and I was way more interested in her than Dennis Liotta. Ultimately, we were married and have been married since 1981, so we all sort of feel we’re family. Over the ensuing 35 or so years, Dennis and I worked on a lot of projects together.
University advantage: Being connected to a major research university is an advantage over other drug developing groups when trying to get investors and access to assets. You’ve got the intellectual power of the entire university.
Collaboration: When Dennis made that major step of separating enantiomers (mirror-image molecules) I had moved to Burroughs Wellcome (a non-profit company developing drugs for medical needs in the developing world) and was in the division of virology, so it was a natural thing for us to get together. Working with Dennis was very easy for me. First, we were friends, and second, Dennis is a good-hearted guy so he’s easy to get to know and to interact with. We formed a somewhat seamless relationship between Dennis’s group at Emory and the virology group at Wellcome and we worked very, very well together in generating the data and getting the drug positioned to move into clinical studies.
Resistance: To test resistance, you grow virus in cells—in this case it was HIV—and put drug on them and then isolate virus that’s been exposed to drug and you re-infect cells and expose it again to drug, and that’s called serial passage. Over time, populations will emerge that are resistant to the drug. Some amino acid change will occur that renders the virus insensitive (phenotypic insensitivity.) Well, with emtricitabine, that only took one passage. And we were like, “Oh my God, it isn’t going to last a week.” Furthermore, there was some evidence emerging out of the lamivudine trials that were ongoing that patients were breaking through. People look at pharmaceutical companies and think wow, they’re like the Roman army, there’re in a phalanx and they’re all aligned. Well that isn’t necessarily true. There was rivalry between the U.S. and UK divisions. And they didn’t hesitate to call up and tell us that the drug wasn’t going to make it. So I passed that on to Dennis.
Risky business: In this business you can invest two to three hundred million dollars and 10 years of your life, and you wake up one morning and it’s all gone. This risk leads to a lot of reluctance to invest, and demand for a high return, which leads to expense. All of these pieces of the story are tied together—none of them function independently.
Keep on keepin’ on: My wife threw a surprise 60th day party for me, and a lot of people involved in the drug project were there. I looked around and realized how many millions of lives they had all impacted positively. People realized the impact they could have… knowing what they were doing was a real motivation.
The aha moment!: Out of that experience came the idea of combining drugs. The synergy between AZT in those patients and FTC was an enormous breakthrough. It led to the first combination drug, Combivir, which was the first fixed-dose combination pill. The precedent for combining drugs against drug resistance had history in cancer and even in antibiotics so there was precedent that suggested that might be the way forward. Molecular virology was progressing, understanding of DNA and RNA sequencing was progressing, so we began to find the resistant genotypes and were able to isolate the virus. That led to being able to test drugs in combination. This provided treatment for people who had exhausted their options. Now, no drug is approved for use by itself. They’re all approved for use in combination. Now if you look at antivirals, combination therapy is standard of care, it’s more potent.
We are family: One of the most interesting times for me was being deposed in patent suits. And of course, I was at the heart and soul of this, and was a favorable witness for Emory. This young woman was interviewing me, and she asked me, “How did you become friends with Dennis Liotta?” As if it was some sort of conspiracy starting in 1976. They have a tone, you know. And I said, “Well, I didn’t really care about Dennis Liotta.” And she got a rather shocked look on her face and said, “What do you mean?” I said, “There was a woman up in his lab and I was interested in her, so I had to become acquainted with Dennis Liotta.” And she said, “Who is this woman? “And I said, “My wife.” And her assistant said a four-letter expletive. And then afterword, I saw him and he said, “You know what, you guys are tight, this is all family.” And I said, “Yep, you know, you’re right.” I don’t have any regrets about the path I took.
Go here to watch the stories of those involved and those who benefited from the discovery of 3TC & FTC. Go here to read the full series of blog interviews with inventors, patients, and others.