Evolution of an Epidemic: Taming a Killer Virus

AIDS—acquired immunity deficiency syndrome—was named in 1982, at the beginning of the epidemic in the U.S. It was another two years before it was known that human immunodeficiency virus (HIV) was the cause of this strange new disease. Death rates rose steadily and steeply over the next decade. By the mid-1990s, AIDS was the leading cause of death for Americans ages 25 to 44 and more than 250,000 people had died from AIDS or AIDS-related causes.

“Some of our most creative people were taken away from us by this terrible disease,” says Emory synthetic chemist Dennis Liotta. “I became increasingly convinced that I had to do something that would make a difference, even though I didn’t know anything about virology. That was my driving force for getting into it and I never looked back.”

HIV virusDeath rates began to decline after multidrug therapy became widely available. Emory researchers were front and center in the discovery of this therapy.

“At the time, we didn’t know too much about HIV. We didn’t know if it was a respiratory virus, we didn’t know if it would affect us personally. But we worked on it because there was a need and an urgency,” says organic medicinal chemist Raymond Schinazi. “When you’re young, you want to save the world. We took the gamble and it paid off.”

HIV is now a chronic, not fatal, diagnosis, largely due to drugs made from compounds that emerged from Emory labs. More than 90 percent of people in the U.S. who have HIV, and many around the world, take at least one of the drugs invented by Emory researchers Liotta, Schinazi, and Woo-Baeg Choi.

Liotta, Professor of Chemistry and Executive Director of the Emory Institute for Drug Development, and Schinazi, Walters Professor of Pediatrics at Emory and Director of the Laboratory of Biochemical Pharmacology, are still hard at work, developing other novel therapeutic agents and furthering vaccine development.

Emtriva bottle“This is an incredible example of the impact that academic research can have on people’s lives,” says Todd Sherer, Emory Interim Vice President for Research Administration. “We are very proud that the work by Drs. Liotta, Schinazi and Choi has helped so many people.”

Untold numbers of people around the globe have benefitted from this basic research. Go here to watch the story of how the discovery unfolded, and to see patients whose lives were saved by a dark-horse drug regimen that became the most common HIV treatment in the world. Go here to read the full series of blog interviews with inventors, patients, and others.

Marianne Swanson: The Survivor

Marianne Swanson, a senior staff nurse at Grady Health System’s Ponce Center, was born and raised in Brooklyn, in a close-knit Italian-American family and community. She lost her first husband and two of her three children to AIDS, and she is HIV positive. This is her story:

Starting a family: Jeff and I were in a singing group in a Catholic Church, that was where we met. We fell in love and got married in a small Christian church in Brooklyn. We were married for about two years before I got pregnant with our first son, Jonathan. My second son was born in 1985. I remember we had gone to New York to visit when he was 5 or 6 months old, and a friend of mine had contacted me and told me that he was sick with HIV. It was the first time that HIV hit close to me. I didn’t know at the time, hearing about his illness, that it would even come closer.

HIV positive: Our second son, Joshua Paul, was sick a lot. He was over a year old and started getting swollen lymph nodes and a runny nose. Doctors thought he had a mysterious form of cancer. I guess it was in 1987 that Jeff suggested we get him tested for HIV. Jeff had a previous lifestyle that could be cause for an HIV check-up. Sad to say, Joshua Paul’s disease just got worse and worse until he passed away. After he died, Joshua Paul’s oncologist told us his HIV test had come back positive. I was like, OK, well, during his cancer treatment, he had some blood transfusions. She said they were screening the blood transfusions at that point, so there’s no way he could have gotten it from a transfusion, the only way he could have gotten it was from me.

Marianne & Darrell SwansonFrom me? I was like, excuse me? I had always been the wife of one person, faithful to my husband, I’m not a gay man, never had a blood transfusion. What happened? How could this have come to our family? We were advised by our obstetrician and different doctors that all of us get tested for HIV. It was a very long, drawn-out process back then. Jeff tested positive for HIV, I tested positive for HIV. Jonathan, my oldest son, was HIV-negative. I was pregnant at the time with our third child, and the fate of our unborn child was unknown at the time. There was a 50-50 chance she would be positive. That was a grief-filled period.

Holding out: In 1987, my daughter Annalisa was born. She was sick from six weeks of age and was diagnosed with full-blown AIDS. So that was really a hard pill to swallow. After Annalisa passed away, Jeff’s health started to fail. We were just sort of holding out, we knew that there were a lot of things scientists were working on to try to develop a therapy for HIV. It was a little bit too late for Jeff. When combination therapy came out, he was already in hospice care. They did try to put him on an experimental therapy, but he couldn’t eat, couldn’t swallow, never really worked for him. Jeff passed away in 1996.

Remarkable recovery: I feared that I was going to be next. I had just watched everyone wither away and die. I had only 73 T cells. But I was not about to let my last child become an orphan. At the end of 1995, I went on combination therapy—Combivir, AZT and 3TC with crixivan—and showed a remarkable recovery. My HIV became undetectable and my T cell count was above 200. Now it is in the 600 range. I’ve been undetectable ever since. For me, the therapy that came out at that time was literally a lifesaver.

Figuring out a future: I was diagnosed in 1987 but I knew I had it in 1985 because that’s when my son was born. So now here it is, a decade later, and they’re saying, here are these drugs, you’ve got to live, now figure out your life. What does living look like now? Part of living for me was always being involved in a church. I started teaching Sunday school in a church singles group. Everybody in my church, everybody in the singles group, knew about my HIV so I’m like, OK, I’m not here for a man, I’m just here for friends. I told myself I’d be a single parent forever.

Met a guy: There was this guy that I became friends with in the singles group and he kept looking at me with these eyes that didn’t look like friendship eyes. I was like, wait a minute, no, back off, we’re just friends. Anyway, Darrell Swanson entered my life and started pursuing me in a romantic way, which felt so unusual to me because I hadn’t done that for years. He didn’t mind my HIV status. Lo and behold, in June 2000 we got married and have been married ever since.

Back to work: When my son went to Georgia Tech, I went back to work. I always said I wanted to work at Grady, at the Infectious Disease Clinic. I was a patient there and they saved my life. I’ve chosen to do battle as a nurse in HIV care. Now, young people are getting diagnosed without a knowledge or the experiences of the HIV crisis. Some have a hard time maintaining their medicine regimen. They need organizational skills, help with paperwork. And there are still people who are getting diagnosed too late and dying.

Status update: I went from a very complex regimen to a very simple one. I developed some resistance, so I take an additional pill, but it’s still pretty simple. This is all just routine for me. I don’t feel like HIV controls me, I feel like I control it. I’m a warrior.

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.

Nina Martinez: The HIV Positive Twin

Public health analyst Nina Martinez is 35 years old and has been living with HIV for all but six weeks of her life. Her father was active duty Navy, and she’s a twin. She has HIV while her twin does not. This is her story:

How it happened: My twin and I were born 12 weeks early and at that time in the mid-1980s you needed to take a lot of lab work. Because they took labs so often, we were both anemic. We required blood transfusions at 6 weeks old. I was transported to San Francisco and she remained at San Jose, so we got transfusions in two different cities. I ended up with HIV and she did not.

Diagnosis: I didn’t know I was HIV positive until I was 8, in 1991. I got chicken pox like everyone else. It was just an accident that I was tested and a complete surprise. It turned out the Department of Defense knew for a year and a half that the donor from 1983 had tested positive. They had sent a letter to Hawaii, but my family was living in New Jersey then and didn’t get it. After I was diagnosed, I started taking AZT (azidothymidine).

Nina Martinez

Photo credit: Johnnie Ray Kornegay III

Magic Johnson and me: When Magic Johnson made his announcement, I was diagnosed about a month later. That’s the only association I had with it. I honestly believed that Magic Johnson and I were related. I needed someone to look up to. I would go around and tell my classmates that Magic and I were related, and they were very confused.

School days: At 8, you don’t know what HIV is, you just know what you hear on TV. My classmates would tell their parents that somebody at their school was living with HIV. Parents at that time just didn’t want me to go to school with their kids. But thankfully it was against state law to discriminate against children living with HIV.

Teenage rebellion: I used to flush bottles of medication down the toilet as a teen, rebelling to the regimen. I was angry that the responsibility was being put on me. The teen years are hard enough without adding a chronic illness on top of it. At 16 it was quite overwhelming.

Unexpected adulthood: Around that time, I had access to the internet, which was such a huge learning experience. It really shortened the distance between people. I didn’t meet anyone else with HIV until I was 17, despite having it my entire life. My childhood, I was told that I was going to die. And then when I didn’t, and I did graduate high school, it was kind of this unexpected adulthood. “What do I do now? I guess I’ll go to college.” It wasn’t the same as for a lot of people, that it’s expected for you to go to college. For me, it was, OK, now that I’ve survived into adulthood, I need to learn how to manage this, and how am I going to provide for myself.

Insurance cap: Everything revolved around my medical care and getting health insurance, and making sure I could take care of myself. That’s one of the reasons I decided to go to college and graduate school—to get on an insurance plan. But health insurance plans back then, particularly student plans, didn’t have the kind of pharmacy cap that would accommodate the cost of HIV drugs. At the time, there was a $1,000 pharmacy cap. Since just one of my medications was $700 a month, I didn’t really know how to make that work. Now, because of student advocates who are living with chronic illnesses, the pharmacy cap is $100,000, which makes access a lot easier—and it makes it easier for you to get through your college or graduate school experience and help set you up for success.

Spreading awareness: While in grad school I traveled about 30,000 miles cumulatively to talk to college students about HIV and HIV prevention. I spoke about non-sexually transmitted HIV and being a lifelong survivor. I wanted to help make sure that people weren’t scared of being tested

What if time is short?: When I finished my coursework, the first person I knew living with HIV died. He was 31 and I was 25. I had never been to a family funeral, so this was my first experience with death. I saw him about three weeks before he died. That shook me, it kind of set me back. I had gotten used to thinking, “Oh, I’m going to have this normal lifespan.” But when he died, I started to think, am I spending too much time on my academic career when I should be out living life? I was offered a job at the CDC, and federal health insurance was better than what I had, so I started work immediately.

Combination treatment: I went on a “drug holiday” between 2006 and 2011, at which point I was ready to go on combination pills. I took Trizivir, which had 3TC (lamivudine) in it, and went from taking four pills a day to two and was able to sleep through the night. Who doesn’t love sleeping through the night?

Treatment: One of the great things about having access to treatment is that you do get to have a somewhat normal life. You wouldn’t be able to tell I have HIV just by looking at me, it would be something that I have to mention. But again, here come these challenging, long-held beliefs—that people living with HIV are supposed to look sick. People think because I don’t look sick, it must not be a problem for me. They don’t realize all the work that had to go into making sure I had access to medication, like running up student loans.

Lingering stigma: The South is the epicenter of HIV, that’s why I work here. People are receptive to my story, they see me as ‘innocent.’ But when I talk about friends who got HIV sexually or through drug use, they judge them. My friends are just trying to live the same life that I’m trying to live. There is still just that stigma we have to chip away at. Everyone just needs to meet someone with the disease.

Misperceptions: Because people only see what they see, that’s where you get the common perception that HIV is not a big deal, because people think all you have to do is take a medication and then you’re done with it. But they don’t really understand all the economics that go into that. They don’t understand what HIV stigma looks like: the fact that we’re still placing labels on people living with HIV, like, ‘they deserved it,’ or that they’re ‘dirty.’ There’s still this visceral reaction when somebody says they are HIV positive. I get a lot of ‘I’m sorry.’ What are you sorry for? That I lived? At its core, it’s a virus. We should treat it as such.

Overcoming illness: I’ve run five half-marathons and the Marine Corps marathon. I realized that even I had my own internalized stigmas. I thought I’d never be an athlete. I ran for charity, to raise awareness of HIV and also for HIV charities. And as a nod to Magic Johnson. It’s almost like a celebration of my body, paying respect to everything that it’s been through and the fact that it can still do more than I think it can.

Advice to younger self: If I wrote a letter to my newly diagnosed self, the top things I would say are:

  • You’re not going die anytime soon

  • People will say hurtful things, so be prepared

  • People living with HIV are part of the solution not the problem

  • You are probably not related to Magic Johnson

  • Don’t flush your medication down the toilet

  • Just go out there
  • Stigma is going hurt, but it hurts more not even trying to do the things you want to do

Fun fact: I taught Peter Piot, dean of the London School of Hygiene and Tropical Medicine, and co-discoverer of Ebola, the Macarena at the Googleplex, of all places.

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.

Addendum: Nina was the first HIV-positive woman to donate a kidney to a HIV-positive recipient, read all about it in this CNN story.

Dennis Liotta: The Chemist

Synthetic chemist Dennis Liotta, PhD, Samuel Candler Dobbs Professor at Emory and executive director of the Emory Institute for Drug Development, is the co-developer of an antiretroviral drug that has saved the lives of countless people living with HIV around the world.

Starting out: Liotta says he was “genetically coded to be a chemist.” Not only was he naturally drawn to the field, he was able to follow the footsteps of his oldest brother, an organic chemist at Georgia Tech. “Charles was my first scientific role model,” Liotta says. “He is one of the most gifted teachers I’ve ever seen. He has a knack for being able to take even the most complex subject and translate it down until you understand it. He’s just remarkable.”

Dennis LiottaPath to academia: He never deviated from his desire to be a chemist—but he did find it a bit difficult to focus for a few years in college. “I got rejected by most graduate schools so quickly, I didn’t even know post mail could go that fast,” he jokes. CUNY had the foresight to accept him, however, and he was soon back on track. “It never really occurred to me that I would ever be anything other than a professor. I interviewed at some pharmaceutical companies. They were perfectly fine, with smart people. But I wanted to do my research, I wanted to teach,” he says.

Novel compounds: Liotta came to Emory in the late 1970s, at the time a “regional university with a few pockets of excellence.” The camaraderie appealed to him. “You can make up your own research structure. The collective wisdom and creativity of the group is allowed to emerge,” says Liotta. He began developing new methods for making novel compounds. “It was like a candy store,” he says. “I’d think of ideas and we would try them.” He gained a reputation as one of the most creative synthetic chemists working on antivirals.

A new epidemic: In the mid-1980s, the magnitude of the AIDS crisis was starting to become apparent. “Some of our most creative people were taken away from us by this terrible disease,” he says. “I became increasingly convinced that I had to do something that would make a difference, even though I didn’t know anything about virology. That was my driving force for getting into it, and I never looked back.”

FTC Structure

FTC Structure

Fortuitous partnership: Liotta began working with Emory Professor of Pediatrics Raymond Schinazi and post-doc Woo-Baeg Choi and found an affinity for drug development. “There are a lot of hurdles to finding something that could be potentially a drug, and each time you’re able to figure out how to get over that hurdle, that’s very satisfying,” he says. “Emtricitabin (Emtriva) was important because it not only had the good potency and good safety profile because it paired up well with other drugs,” he says. “Because of that pairing, we were able to take AIDS from a death sentence to a manageable chronic disease.”

Still hard at work: Liotta is not content to rest on his laurels—he is still hard at work at Emory and through partnerships around the world and is hoping that scientific research will eventually lead to a cure for HIV as well as treatments and cures for other neglected diseases.

With a little downtime: He enjoys spending time with family and friends and cooking on the grill—a friend gave him a grilling apron with the title “The Grillfather.”

Sharing credit: Liotta may be one of the only synthetic chemists who is regularly recognized in public. A sampling of encounters: At a restaurant with his wife, their waiter thanks him for his discovery, saying, “I’m on that drug and it’s changed everything for me.” A close personal friend on Emtriva is flourishing. Mothers thank him for saving their sons’ lives. While proud of his contributions, and deeply touched when he is thanked by someone whose life has been saved or transformed, Liotta is quick to spread the credit around. “Thousands of dedicated scientists had their fingerprints on this drug development process,” he often tells a grateful recipient. “While you’re being thankful, let’s thank them all.”

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.

Raymond Schinazi: The Virologist

Organic medicinal chemist and virologist Raymond Schinazi, PhD, the Frances Winship Walters Professor of Pediatrics at Emory and director of the Laboratory of Biochemical Pharmacology, was born in Egypt to Italian parents. In 1962 his family was threatened by the Nasser regime and immigrated to Naples as refugees. He went to boarding school in the UK, where he was a chemistry major at Bath University, and later came to the U.S. and studied pharmacology at Yale University before beginning his career at Emory.

The path to chemist: I was actually pretty good at chemistry. I wanted to by a physicist, but because of my background coming from a Middle Eastern country, I couldn’t really walk into a nuclear reactor and work on radiation, bombs, and things like that. I was very talented in physics but I got blocked from doing this because of my circuitous route, going from an immigrant, to a British student, and then an American student. So basically, I had no choice but to go into chemistry. It ended up being a good choice for me, though, since I worked on natural products first, and subsequently on nucleosides, which are basically the building blocks for DNA and RNA. If you think about it, just about every virus on this planet has DNA or RNA.

Raymond SchinaziMy mentor: At Yale, I worked with William Prusoff (“the father of antiviral chemotherapy”), who developed the first drug for herpes of the eye. When I started my career at Emory in 1978, I was working on combination chemotherapy drugs for herpesvirus. Unfortunately, at the time, even for herpes, people didn’t believe in combination therapy for viruses. We already had combinations for TB and cancer, but nobody believed you needed them for viral infections.

Academia versus industry: I’ve always been in academia, never had a real job in industry, trained in industry but I never actually took a job with a salary from industry, ever ever, but I also realized rather quickly academia is not a great place to develop drugs once you’ve discovered them.

Proudest career moments: Our background in nucleoside chemistry propelled us to the front of the line, and laid the foundation for what we know today. We were the first to, for example, set up the first HIV lab at Emory University. At the time, we didn’t know too much about HIV. We didn’t know if it was a respiratory virus, we didn’t know if it would affect us personally. But we worked on it because there was a need and an urgency. When you’re young, you want to save the world. We took the gamble and it paid off.

3TC Structure

3TC Chemical Structure

I worked with Dennis Liotta for several years developing antiretroviral agents. Probably one of the most successful was FTC (emtricitabine), a very powerful anti-HIV drug that’s used widely in many drug combinations today for HIV. About 94% of people with HIV take one of our drugs invented at Emory. The other drug was 3TC (lamivudine). This led to a whole plethora of compounds. Subsequently we moved on to Hep B, because we found that some of our HIV compounds were also effective against it, killing two birds with one stone.

A lot of scientists discover things that sit on a shelf. I couldn’t tolerate that so I took the risk to move the compass, even using my credit card, to be able to form companies like Pharmasset, that became hugely successful and eventually sold for $11.4 billion—that’s billion with a “b” not an “m”. The company sold 13 years after being founded, that’s pretty fast. There were a lot of bidders, a lot of interest. Today our drugs are widely used and have saved millions of lives. When I wake up in the morning, I’m really happy to have saved so many lives. Not only me, but also my collaborators, we all worked together on this, industry, academia, advisers, consultants, medical teams, everybody was involved in this. Success is not really measured by the amount of money you make, it’s by the lives that you save.

Advice to young scientists: Keep trying, I have failed many times. I have drawers full of grants that never got funded. If you have a good idea, follow your heart and follow your brain and be stubborn and persist and you’ll get the funding.

Meeting people saved by your drugs: My cousin died of HIV in 1990 and it was devastating to me. A patient—a person I should say, because they’re not patients anymore—who takes our drugs has the opportunity to live longer. When they are revived, it changes everything for them. It’s like going to church and getting a wafer, you’re saving them in more ways than one. The (antiretroviral) drugs saved our florist’s boyfriend, and I get a lot of flowers for very cheap.

Fun fact: I’m an avid fisherman, I enjoy catching trout in North Georgia as well as deep sea fishing. Catching a fish is very similar to developing a drug, you throw in the bait, you hope a big fish hooks it, and then you have to reel it in. You’ve gotta realize the fish is there.

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.

George Painter: The Corporate Partner

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.

George PainterUniversity 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.

CombivirThe 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.

Jeff Lennox: The HIV Physician

Jeff Lennox, MD, is an Emory professor of medicine, Emory chief of internal medicine at Grady Memorial Hospital and the former medical director of the infectious disease program at the Ponce de Leon Center. “At Grady, we see patients from every continent except Antarctica, so we take care of patients with a wide variety of infectious diseases,” he says.” In addition, Grady has one of the largest populations of HIV-infected patients in the United States.” Here, Lennox tells how he came to specialize in infectious disease and HIV. 

A new disease: As a medical student, I was fascinated with bacteria and how infections circumvent our immune system. In my second year of medical school, there were reports from San Francisco and New York of a group of patients who had a new syndrome of acquired immunodeficiency. At first, the thought was that it might be due to a known pathogen, a toxin exposure, or possibly to an unknown infection. There was a nervousness among healthcare personnel about such a mysterious ailment.

Jeff Lennox

Pessimism prevailed: Once the viral cause was discovered, people could better understand it, but there was a lot of pessimism around viral infections. They were difficult to treat effectively. The pessimists, luckily, were ultimately proven wrong. The success of HIV treatments shows you the amazing things that medical technology can do in this modern era.

First treatment for HIV: There was essentially no treatment for AIDS until 1987 following the approval of Zidovudine (also known as azidothymidine, or AZT). When it was approved, it brought a lot of hope to people, but it was a very difficult medicine to take. Side effects included nausea, headache, anemia, and it had to be taken every four hours. Initially it only added four months of life for the average patient.

More breakthroughs: Doctors began checking for the amount of virus in the blood, so they were able to tell more accurately if a medicine was working, as opposed to waiting for results of one- to two-year-long clinical trials. One of the reasons I came to Emory is because Emory investigators contributed to the development of 3TC. In 1995, lamivudine (also known as 3TC) was introduced. It showed strong promise when combined with other drugs. In 1995-96, a combination of Zidovudine, 3TC, and a protease inhibitor was a huge step. It reduced viral load to undetectable levels, patients’ T-cell levels actually went up, and death rates fell.

Eureka! When we first saw this data, short of my wedding day and the birth of my children, this was the most euphoric moment in my entire life. All at once it was clear that we could offer patients real, long-lasting benefits.

AtriplaDown to one pill: The next major breakthrough was the introduction of integrase inhibitors. They are nontoxic, very potent, and rapidly reduce the viral load—in two to six weeks it becomes undetectable. Now, more than 90 percent of people with HIV start treatment with just one pill once a day that includes an integrase inhibiter, and obtain an undetectable viral load.

A cure? Not yet. But let’s just say that 10 years from now in 2028, I can’t even imagine the technology were going to have. If you had told me in 1998 what we’d be doing now, twenty years later, it would’ve just amazed me. I mean, I couldn’t even have comprehend some of the things were now doing, so I’m very hopeful for the future.

Crossover impact: With virus treatments, many times there are benefits that help other diseases. For example, 3TC and FTC help against hepatitis B—the World Health Organization has 3TC on their list of essential medicines because of activity against both HIV and Hep B. Medications are being repurposed to see if they will help patients with HIV, not by attacking the virus itself, but some of its symptoms. Researchers are also testing treatments to prevent HIV associated bone fractures, and statins used to prevent heart attacks are being tested in HIV infected patients.

Innovative care: The Ponce center was purchased for a dollar. There was some resistance to having an HIV treatment center in Midtown Atlanta, but people rallied, put up signs. Once opened, it was one of the most innovative HIV care centers in the U.S. It offered treatments for cancers associated with HIV, dental care, psychiatry, a pediatric unit, even a food pantry and assistance with transportation and housing. The Ponce Center itself is a bright, colorful, cheerful building, with donated artwork. There was a coming together of the community to really try and provide an environment where patients felt like people were caring about them and caring about the fact that they were suffering from AIDS. Only the sickest of the sick were funneled into the Ponce clinic, making it unique. The center partnered with the AIDS Clinical Trials Group, which was an NIH-funded research group testing breakthrough therapies.

Current research: I am researching acute HIV—when you first get the virus. There is evidence to show that treating people very early on might lower the number of latently infected cells, which could help with cures in the future. I am also testing medications for cure strategies, and medications for preventatives. Currently a combination of FTC and Tenofovir, taken together, prevent someone from getting HIV. We are also testing injectable antivirals, so no pill has to be taken every day, and injectable antibodies that might be able to prevent HIV.

Why are there still AIDS cases? Some patients are not completely adherent to treatment, some have no insurance and no access to treatment. People who are not on treatment can pass the infection on to others.

Advice to younger self: Find something you’re passionate about and pursue it. Also, throughout life, keep an open eye for unexpected paths that lead you to your goals.

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.

What Does Mixing Math, Physics, Computers, and Imagination Give You? A Pioneer in Radiation Oncology.

Ian R. Crocker, MD, FACR, is a radiation oncologist specializing in brain and eye tumors, who worked at Winship Cancer Institute for over 30 years. Throughout his career, Crocker was an active member of multiple innovation and research teams that sought to develop new medical technologies and methods to improve treatment outcomes and patient care. Some of his most notable successes include his co-invention of the BetaCath system to prevent the re-narrowing of arteries after an angioplasty and his involvement in the Emory start-up, Velocity Medical Solutions, which produced new, widely used imaging software to improve cancer treatment. Now retired from Emory, Crocker continues to be involved in medical innovation by continuing his work for Velocity under the larger umbrella company of Varian Medical Systems.

What drew you to radiation oncology?

I always found the field of oncology to be very interesting because there was a lot to be done to improve it. When I was in the first year of the medical oncology program I was exposed to radiation oncology for the first time. I loved that it combined math and physics and computers, things that I was interested in and curious about. So rather than pursing medical oncology, I chose to transfer into radiation oncology.Ian Crocker

I finished my residency in radiation oncology and took a faculty position at Duke University for three years. In 1986, I came to Emory, which at that time only had a very small radiation oncology department. At first, when I started seeing and treating patients at Emory, I would see anyone that walked in the door including pediatric and adult patients, all with different types of ailments. There was not really an opportunity to specialize in any area. But over time, I restricted the types of patients that I saw to adult patients with certain conditions.

You worked both in a clinical and research setting, how did you balance the two and what were the challenges and rewards of working in both practices?

I loved patient care and I found it very rewarding. Patients by-and-large were very grateful and appreciative of everything that we did for them and what is not to love about that? In working with patients, I saw the need to improve and change things about existing treatment methods. I would say that my clinical work helped inform my research and vice versa. They were complementary of one another.

What has your involvement in commercialization been during your career?

In academic medicine, there is an underlying interest in research and teaching as well as clinical care. When I came to Emory, I initially became involved in an ophthalmology project that was looking at whether radiation could help fix retinal detachment. Our study indicated that the radiation seemed to work great. But I later found out that the study was only meant to be a lab experiment and it was never meant to be used as a patient treatment. I was disappointed because I was hoping that we were doing something that would help people.

Fast forward a couple years and a cardiology fellow from Israel named, Ron Waksman, asked me whether I though radiation could be used to prevent the re-narrowing of arteries after a coronary angioplasty. I told him that I thought radiation could help and I had in mind a system to combat the issue. But, I emphasized that if we found radiation to be effective, I wanted to see it translated into patient care. We did the animal experiments and radiation worked great. We decided to work with this small start-up company in Atlanta called Novoste to help further develop our product, with the goal of launching a clinical trial and receiving FDA approval for that product. In the end the product reduced the occurrence of re-narrowing from 80% to about 10-20% and really changed a lot of people’s lives.

After that I became involved in more attempts to develop and commercialize products to improve patient treatment and care. The next thing that I worked on was macular degeneration, the most common cause of blindness in adults after diabetes. I believed that applying radiation to the area where the blood vessels were proliferating, the cause of this type of macular degeneration, would reduce the incidence of blindness. I worked with two separate companies to develop radiation devices to be used in humans to halt macular degeneration. Although these showed efficacy, they never received U. S. Food and Drug Administration (FDA) commercial approval due to the development of a drug that was equally effective and easier to administer.

After this I embarked on research with Tim Fox, PhD, formerly with Emory, in automating the radiation planning process. We received funding from the Georgia Research Alliance (GRA) to create a company, Velocity Medical Solutions, to do this. We ended up not developing the automated radiation planning software, but instead developed a product which would allow physicians to use biologic information in the treatment planning and follow-up process. The product is FDA approved and is now installed in over half the top 50 cancer centers in the U.S. It was so successful that Varian Medical Systems, the biggest manufacturer of radiation treatment, came along and bought our company two years ago. I recently retired from Emory but have now resumed working with the Velocity group, helping them create new products for the market place.

What have you found most satisfying in being part of the innovation teams and being one of the first doctors to implement these new innovations?

I love having the opportunity to use my imagination. Medicine is in general very deductive. It is like being a detective and trying to uncover what the problem is so you can do something about it. Trying to imagine or invent a solution to a problem uses a whole different skill set. It allows you to think outside the box and I like that.

I am proud of being one of the first doctors to use the technologies and methods that I helped develop. But, I am probably prouder of having created the products and brought them to the market place, because when you do that anyone can use the product and even more patients can benefit.

You are a founding member of the Emory start-up, Velocity. What was your experience of getting that project off the ground l like?

It was hard. We had an idea for a product that we thought was needed. We had a bit of intellectual property around our ideas and GRA awarded us some funding to help commercialize those ideas. Unfortunately, it was not near enough money to finalize the product, get it FDA approved, start selling it and trying to develop a successful company around it. But, we believed enough in the company and the idea that we put in our own money. I still had a full-time job at Emory and when I finished work there, we would get together and work on company related issues. This was both stressful and rewarding. At the start, it was a month-to-month question of whether the business could stay operational. But, we managed to make the money last until we could turn a profit. We were lucky that many people saw the value of our product and purchased it as soon as we started selling it.

How has your work in the field of radiation oncology changed over your time in practice and how do you think it will change in the future?

The practice of radiation oncology today is completely dissimilar to what I learned as a radiation oncology resident. The roles of the personal computer, imaging, 3D visualization of the treatment plan, and the capacity of newer treatment machines to deliver precision radiation treatments are developments we could not have imagined when I was in residency. I feel very lucky to have been at an academic medical center where we were involved in implementing and practicing these new medical advances. I got to be part of so many firsts in my field like the first image guided radiosurgery.

Moving into the future, one of the projects that I am working on is using imaging to characterize the biology of a cancer much like people in genomics do to predict how a tumor might grow. There is this developing field of radionics which looks at the imaging characteristics of a tumor and trying to predict how it might grow and respond to treatment. I think this is going to be important moving forward.

Who has influenced you the most in your career and why?

The person that inspired me the most was the former head of Radiation Oncology at the Princess Margaret Hospital in Toronto, Dr. Bill Ryder. When I began training people did not know what you could and could not accomplish with radiation treatment. Unlike many people who just stick to established guidelines, Bill Ryder was someone who explored what you could do with radiation. He was on the forefront of multidisciplinary cancer care. He used to have a clinic for residents called the “odds and sods” clinic, where he would show you all these advanced cancers that he had taken on, treated and cured, when others had labeled them incurable. He made me believe in radiation and what it might accomplish.

What would your advice be to your younger self?

I would tell myself to balance my life a little bit better. It takes a lot of time away from family and friends to be at the forefront of new developments in any field. When I look back on it, maybe I tried to do too much.

Tell me something about yourself that many people do not know.

When I was growing up I raced sailboats competitively and at one time was a Canadian champion in sailing. I got invited to try out for the Canadian Olympic sailing team. The same day I got that invitation, I was also accepted to medical school. I showed my mother the letters and she took the Olympic sailing one and ripped it in half and said, “You’re going to medical school.” I think she made the right decision for me.

Lessons from Baseball: Applying Passion and Competitive Drive to Radiation Oncology

Tim Fox worked at Emory University as an Associate Professor & Director of Medical Physics from 1994 to 2014. In 2005 he and three of his Emory colleagues created the Emory start-up, Velocity Medical Solutions, which built and sold a multimodal medical imaging software. Velocity was later acquired by Varian Medical Systems and in 2014, Fox left Emory to accept a full-time position as the Associate Vice President of Imaging Informatics at Varian. Fox grew up playing baseball and now applies that same passion and drive to his entrepreneurial endeavors Just like the famous line from the baseball movie, Field of Dreams, Fox is living proof that “If you build it, they will come.”

What drew you to radiation oncology?

It was the combination of technology and medicine. It was the one area back in the 1990s where you saw computers being applied to the diagnoses and treatment of patients.

How did you move to software and cancer imaging informatics?

I always loved computers and started to become interested in them when I was 15 years old. When I got to college I majored in physics and minored in mathematics and computer science. I wanted to focus on the computational and software side of physics. I later found medical imaging and software projects in nuclear medicine and radiation therapy.

Then when I came to Emory I used my computer skills to build software programs like the radiosurgery treatment planning system, a computer oriented optimization program, and advanced molecular imaging software. Back in the 90s, computers were still evolving, so you often had to build these tools yourself, which is what I did. Over my career, I developed a philosophy about identifying problems and building products and solutions to fix those problems. Being part of a cancer care team in the clinic and immersing myself in daily challenges allowed me to observe an inefficiency in existing cancer imaging techniques and inspired me to build a solution to that problem.

Did you always know that you wanted to apply your computer skills in a medical setting?

Tim Fox, PhD

Tim Fox, PhD

No–my senior year as an undergraduate, I participated in a summer internship program at Oak Ridge National Labs in Tennessee where I was able to study nuclear physics doing particle simulations with computers. Working with PhD scientist, I learned about the field of medical physics, and I applied to a graduate research assistantship at Georgia Tech in 1990 to further pursue this field.

Who has influenced you in your career the most and why?

I think it would have to be my parents. They always said “Go get as much education as you can. No matter what you want to do, go and get all the education you can in that area.” They instilled in me the desire to attain the highest level of education possible. I always knew that I would do an undergraduate degree and then of course, graduate school.

Describe the development process for your software.

In 2005, we started Velocity Medical Solutions and approached some large companies with the idea of using PET imaging to improve cancer treatment planning. But, none of them were interested in working with us on solving the problem. Eventually, we approached the Georgia Research Alliance (GRA) and got a commercialization Phase 1 grant and decided to build the software ourselves, knowing that at the very least it could improve research and clinical care at Emory.

Our small team set up a series of smaller milestones. The first milestone was to build a solution to using PET imaging in treatment planning and create a business plan. The next milestone was to see if we could receive Federal Drug Administration (FDA) clearance, which would allow it to be sold on the market. This was probably the biggest hurdle we had to overcome. We got our first 510k FDA clearance in 2007 and our second in 2008. Our next milestone was to see if we could get a cancer center to purchase our software. We hired a team and started to commercialize our platform.

Your technology was licensed to an Emory start-up – what was that experience like?

There were both upsides and downsides to building our company; academics and industry do not always mix well, especially in the field of health care.

We did not think about everything at once, but set small milestones using the GRA Phase 1, 2 and 3 grant program. GRA was a game changer and a big supporter through the whole process. Without them we would have never made it. It allowed us, as university faculty members, to take the ideas and intellectual property we had and to actually build the technology. They helped us make the leap from having this great idea to having an actual technology.

A challenge that we encountered as faculty members at academic institutions was managing conflicts of interest between the university and entrepreneurial endeavors.  In the past, the word “commercialization” was typically viewed as a problem.  Today, the National Cancer Institute (NC) sponsors Academic-Industry Partnership grants since we realize that it does take a partnership to move ideas from the clinic to patients.  Being able to manage the conflicts of interest with the GRA Phase 1, 2 and 3 program presented obstacles along the way, but we worked through them with Emory and OTT.

Aside from the challenges, I love that this has been an opportunity for me to combine life sciences, computer technology, and medical healthcare. This startup and my transition to working for Varian Medical Systems has allowed me to continue to work on products in the field of cancer therapy. I think this type of innovation would be impossible without the growing relationship between academia and industry, which supports and expedites the innovative process.

What made you decide to follow your technology into the corporate world and how has that transition been?

After working at Emory for 20 years, I decided to leave to work for Varian because I recognized the need for partnerships between academics and industry. I knew that I could understand both sides of this partnership and hopefully facilitate and nurture it.

Additionally, I had worked with Varian over the years through Emory. Therefore, I was familiar with Varian’s team and technology development. I saw this job change as a new opportunity and new challenge that I wanted to explore. I definitely miss academic medicine, but I wanted to focus solely on building software.

What have you found most satisfying in seeing your work reach the marketplace and help patients?

It’s wonderful to go in and see people using the software. It is even better when users show us patient cases where they have used the software in ways that we did not anticipate. We built Velocity to address one initial problem, but people are applying it to other problems, which helps us figure out how to further improve and expand our software. From working in industry, I have come to appreciate that we provide physicians with tools and they get to use them in a multitude ways to help their patients.

Where do you see imaging in the oncology field going?

We like to say “seeing a patient is important, but seeing inside a patient is more important.” Medical imaging allows you to see inside the patient in a clear way, whether it is anatomical imaging like computed tomography (CT), which shows structural detail, or more advanced imaging like PET, which shows you molecular metabolic activity. It gives a more defined picture of a patient’s condition.

In September 2016, the NCI Blue Ribbon Panel announced their ten broad Cancer Moonshots. One of those 10 items was to develop new cancer technologies and treatments using new radiological imaging and deriving data from that imaging. That is exactly what we are doing, and we are partnering with academic centers around the nation. In the future, as new types of medical imaging are developed our software will be able to incorporate them and provide more comprehensive imaging package that will improve patient care.

Tell me something about yourself that many people do not know.

I think many people do not know that I played baseball through college and considered being a college baseball coach instead of a physicist. I did get to coach my son’s little league team though, which I enjoyed.

What advice would you give to your younger self?

“Work smart.” It is not just about working hard but being smart about what you are doing. Find what you like to do, but also find where you can add value to a company or a team.

I think it’s important to find a career path and then make it what you want it to be. Find ways to incorporate your passion into your occupation. For me it has been to use my love of teamwork and competitive drive, which I got from my passion for baseball, and use those skills in my chosen profession, and it has worked well.

Treating Anxiety Disorders: Balancing the Real World and the Virtual World

Barbara Olasov Rothbaum, PhD, is the Associate Vice Chair of Clinical Research in Emory School of Medicine’s Department of Psychiatry, a professor in the Department of Psychiatry and Behavioral Science, and director of Emory’s Veterans Program and Emory’s Trauma & Anxiety Recovery Program. Dr. Rothbaum specializes in treatment of anxiety disorders, with a focus on Post-Traumatic Stress Disorder (PTSD). With over 200 scientific publications, Rothbaum has changed the field of PTSD and was a forerunner in the use of virtual reality in treatment of anxiety disorders.

What initially drew you to the field of psychiatry?

I went to UNC-Chapel Hill as an undergrad. I actually went as a math major and that didn’t last long; My freshman year I decided to take a freshman seminar course, which meant there were only fifteen students, on how to design an experiment. It was a psychology course and I had no interest in psychology going in, but it sounded interesting. The course had the kind of teacher you always hope to have, or hope your kids have; the research bug bit me and I loved it. I kept taking more psychology classes and then got involved in research.

Who has influenced you the most in your career and why?

Barbara Rothbaum

Barbara Rothbaum

I learn every day. I learn every day from somebody, from every patient I see. When I think of real turning points; I think of my first professor my freshman year. He changed everything, I gave up all my math courses and went into psychology. When I was an undergraduate, I worked in a fetal alcohol lab under Carrie Randall, PhD, a professor at the Medical University of South Carolina, for a summer. I learned methodological control and precision from her. I also learned that I wanted to work with people after working with animals in Carrie’s lab. Working here at Emory with Michael Davis, PhD, Yerkes Researcher and Robert W. Woodruff Professor of Psychiatry, I started to get into translational research, asking questions of animals and then translating to humans and translating back to animals.

What was the process of integrating virtual reality and anxiety disorder work like?

In 1993, Larry Hodges, PhD, an Associate Professor in the College of Computing at Georgia Tech, contacted me about an Emory-Georgia Tech seed-grant program. Larry specialized in virtual reality and he found out that I was an exposure therapist, meaning that I help people confront their fears in a therapeutic manner. We originally wanted to do the research on fear of public speaking, but in the 1990s virtual reality was clunky. Virtual reality at the time worked more in angles, and people move in arcs. This made it difficult to do public speaking, so we decided to do fear of heights because of the angles and you can easily represent height in virtual reality. Our line at the time was, we “weren’t sure if we were on the cutting edge or the lunatic fringe.”

Could you describe the development process for the first virtual reality treatment incorporating computer scientists and clinical psychology?

Virtual Reality Therapy

Virtual Reality Therapy

I would go to Georgia Tech and I would explain exposure therapy to Larry’s brilliant computer science graduate students to help them understand why people get anxious. For example, we were working on the virtual airplane, there was just way too much room. About half the people who fear flying have a claustrophobia-focused fear that induces panic. Part of the trigger is feeling closed in so you need to remove the feeling of roominess. I would work with the programmers to help them understand the fear cues so they could go back and create them.

Your work has been brought to the marketplace through an Emory start-up Virtually Better – what was that experience like?

The first study was published in 1995, and the response was really amazing. Emory and Georgia Tech thought that there might be a marketable product, so they took us [as inventors] by the hand and drove us to a lawyer to incorporate, and that was Virtually Better. As soon as we incorporated, I received a letter saying that I had a conflict of interest since I was doing research in that area. That freaked me out, and I didn’t understand conflicts completely at the time. I ended up serving on the School of Medicine’s Conflict of Interest Committee for six years. It did limit my research for a while. Now we’ve learned how to manage conflicts; as a result I am able to do more research with virtual reality.

What types of challenges are there for the utilization and growth of virtual reality in psychiatry?

At Virtually Better, we often looked more like an academic department rather than a company trying to make money. This allowed us to get numerous grants, which supported more R&D. Every product we released had good data on efficacy. What scares me now is that people can be working on virtual reality in their garages. We have always had the input from clinical psychologists and computer scientists, we were cutting edge in both fields and releasing what we knew was a good product that a person can benefit from therapeutically. I worry now about quality control and efficacy.

Do you think virtual reality will be a game-changer in Post-Traumatic Stress Disorder (PTSD) treatment?

Well nothing works for everyone. One of the most important things we can have is alternatives and choices. Research has shown that if a patient with PTSD can choose their course of treatment they are more likely to respond positively. With this generation of veterans, which is a video generation, they tend to like virtual reality. It feels a little bit less like therapy to them and feels more “techie.” There was a study done with active duty military populations, that showed that people who feel less comfortable going to therapy would try virtual reality therapy.

What has been the personal satisfaction for you in seeing the progression in PTSD research and treatment?

It has been satisfying and challenging. When I started working in PTSD, there were no indicated treatments, it was just a diagnosis. Psychologists were extrapolating from other treatments for other anxiety disorders. It’s really nice to see that evidence-based treatments for PTSD exist now, but what’s still challenging is that none of them work for everyone. Also, I think some of it is the nature of the beast [with PTSD]. People with PTSD are avoidant; they don’t want to talk about it or go in for treatment. We need to not only develop effective treatments, but also acceptable treatments.

Many who work with PTSD, and other psychological disorders, experience burnout; how do you avoid burnout or compassion fatigue?

I exercise; I do yoga, I ride my bike. We talk about experiences at work in a group setting with supervision as part of the Emory Veterans program. There are some cases that we are talking about that bring tears to our eyes. It’s important that we are able to support each other, it’s not something you can go home and talk about over the dinner table. We hear the worst of the worst. So it’s about work-life balance.

What advice would you give to your younger self?

Problems and roadblocks used to really upset me. I now have the attitude that problems will occur daily, some large, some more manageable, and my job is to navigate them, so I can approach them with more equanimity, wisdom and creativity. I have also had to learn to not take things so personally, for example not receiving a grant or a paper rejection, and to bounce back and start working on the next one. I do give myself a little time (not more than a day) to “wallow” (I wouldn’t use that word for anyone else) following big disappointments. We are only human.

To learn more about Virtual Reality Therapy view our success story. To learn more about Virtually Better go to their website.