Oncology, Etc. – HPV Vaccine Pioneer Dr. Douglas Lowy (Part 1)

Vaccine development is a tremendous scientific breakthrough benefitting countless human lives. In Part 1 of this ASCO Oncology, Etc. Education Podcast episode, you will hear from the pioneering co-developer of the HPV vaccine Dr. Doug Lowy who serves as Principal Deputy Director of the National Cancer Institute , He speaks about how he got into the cancer field through the influence of his parents (4:49), the path that led him to focus on HPV (8:04), and his collaborative professional partnership with fellow HPV vaccine developer Dr. John Schiller (9:31). He also discusses his ongoing trial of one-dose administration, which promises to boost HPV vaccine uptake and reduce the burden of cervical cancer globally. If you liked this episode, please subscribe. Learn more at https://education.asco.org, or email us at [email protected]. TRANSCRIPT Pat Loehrer: Hi, I'm Pat Loehrer. I'm Director of the Center of Global Oncology and Health Equity at Indiana University. Dave Johnson: I'm Dave Johnson. I'm a Professor of Medicine at UT Southwestern Medical Center in Dallas, Texas. Pat Loehrer: And this is Oncology, Etc. Dave, what have you been reading lately? Dave Johnson: Well, you and I have talked about a couple of books, but I thought in light of our guest today, I would mention a book I actually read probably nearly 60 years ago called The Microbe Hunters by Paul de Kruif - very interesting book, written, if memory serves me correctly, in the '30s, about many of the early bacteriologists and physicians who were interested in microbes; Pasteur, for example, and others. And I don't remember all the details, but it certainly was one that was influential for my choice of Medicine as a career, much like Arrowsmith. It was a really impactful book. I doubt many of our listeners today would've read that book, but if one is interested in the history of Medicine, it's a really interesting book to read. Pat Loehrer: You said 60 years ago. Okay, when I was reading books back then, it was about Dick and Jane. Dave Johnson: It's my understanding that you're not past Dick and Jane yet. Pat Loehrer: Good, good point. Good point. Well, it's such an incredible honor today, we have Dr. Doug Lowy as our interviewee today. Doug is the Principal Deputy Director of the National Cancer Institute and Chief of the Intramural Laboratory and Cellular Oncology Program at the Center for Cancer Research. He has served as Acting Director more than any other person - he served as Acting Director between April of 2015 and October of 2017, between April of 2019 and October of 2019, and most recently, he served as an Acting Director until Monday of this week, October 3rd. I had a chance of seeing Doug, I think, about a year ago, a week after he took over, and this is great to have that bookend here. He has had this title of Principal Deputy Director since July of 2010 and he leads many of the NCI's key scientific initiatives. He graduated from Amherst College, I think in Art History, I may be wrong on that, received his medical degree from New York University School of Medicine, trained in Internal Medicine at Stanford, and did a Dermatology Residency at Yale. His focus has been on papillomavirus and the regulation of normal and neoplastic growth. The papillomavirus is in close collaboration with Dr. John Schiller with whom he's co-authored 150 papers over the last 25 years. In the 1980s, he studied the genetic organization of papillomaviruses and identified oncogenes that were encoded by the virus, and he's been integrally involved and instrumental in the development of the papillomavirus vaccine. His laboratory did work with the RAS gene family and other suppressor genes, and as you can guess, he's just one heck of a smart guy. For his body of work and together with Dr. Schiller, they received the Federal Employee of the Year Award in 2007 and the Partnership for Public Service Award, the Dorothy P. Landon American Association for Cancer Research Prize for Translational Research, the Albert B. Sabin Gold Medal in 2011. In 2007, he got the Medal of Honor for basic research from the American Cancer Society, and President Obama awarded him the National Medal of Technology and Innovation in 2014. And in 2017, he received the Lasker-DeBakey Clinical Medical Research Award, which is considered one of the most prestigious honors in biomedical research. He is listed in the Institute of Scientific Information as one of the most highly-cited authors in Microbiology, and obviously, he's a member of the National Academy of Science and the National Academy of Medicine. Although these are notable honors, I'm told that none of them match the opportunity to speak with Dave and I today, and we really thank you so much, Dr. Lowy, for joining us. Thank you. Dr. Doug Lowy: Pat, I am speechless. Pat Loehrer: I so wish that Dave Johnson was, but could you tell us a little bit about your upbringing and your early life? Dr. Doug Lowy: Sure. I grew up in The Bronx, in New York City. I'm the younger of two boys. My brother is two and a half years older than I am. Both of my parents were general practitioners. My parents were both Americans, but my father had a classic sophomore slump when he was an undergraduate and was unable to get into a medical school in the United States. And so, he actually went to medical school in Austria, in the University of Vienna, and needed to learn German in order to go to medical school. But my parents were both very successful private practitioners. They had separate practices but practiced in the same office, and I learned about medicine, in large part, through them. They would go to lectures, and from the time I was probably nine or 10 years old, they would be telling me about cancer, and I became interested in that area. And then, when I was 16, my mother developed a deep melanoma on her leg, and so, cancer literally came home. And luckily, she had very good surgical treatment and lived for almost another 40 years - she lived until she was 80 and actually died of metastatic stomach cancer. But I got involved in thinking about cancer really through my parents. They talked with me about the role of tobacco in the development of lung cancer, and I heard about the Hammond and Horn report from the mid-1950s when it came out. Pat Loehrer: That was when Dave was reading the Microbe Hunters. Dr. Doug Lowy: I was reading it at about the same time. I must say that, although I found it very interesting, it didn't really speak to me, and now that's what I need to go and do. Although, in retrospect, that's what I've ended up going and doing. Pat Loehrer: Was it because of your mother that you had an interest in dermatology? How did you swing into there? Because we think of you mostly as a translational researcher. Dr. Doug Lowy: The dermatology was really when I was at NYU. I worked in the laboratory of Jan Vilcek, who had recently come from Czechoslovakia to NYU, and in his lab was Alvin Friedman-Kien, who was a dermatologist. And Alvin subsequently was among the first people to identify the AIDS epidemic through the Kaposi sarcoma. But Alvin talked with me about dermatology, and potentially, this might be an interesting field for me to go into. And then, when I went to Stanford, I did Internal Medicine for internship and a year of Medicine, and I did a rotation in Dermatology. And I was very impressed that the people who smiled the most were the dermatologists. And they had time also to think about what was going on with patients. And since I was at Stanford, it was a tertiary care facility and so we were taking care of people who were terribly sick, largely people with lymphoma and other types of cancer. And I thought that I might be better suited to taking care of people who were less sick than that. Dave Johnson: Is that where your interest in Papillomavirus started? Dr. Doug Lowy: Well, that was indirect. I first went into dermatology and then said, "Well, I want to be doing research. What can I do in research that might be connected both with dermatology as well as with cancer?" And the closest that I was able to come was Papillomaviruses. And when I started working on them, they were not yet clearly associated with cancer the way they are today. It was known that they were associated with an uncommon condition called Epidermodysplasia Verruciformis or EV and this is a condition where people have widespread HPV infection. And on sun-exposed areas, a subset of them develop skin cancer, but it's distinctly uncommon. The real interest, if you will, came from the identification of HPV infection and cervical cancer, which is one of the more common cancers, especially on a worldwide basis. And that was really the link with cancer. Pat Loehrer: You had an incredibly long-term collaboration with John Schiller, and as I mentioned, you published more than Dave and I have written letters to our wives with this man. Tell us a little bit about that relationship, that friendship, and that professional partnership. Dr. Doug Lowy: John, actually, he was at the University of Washington in Seattle doing his PhD, and it was so long ago that he sent me a letter, and I had been doing research on retroviruses. He sent me a proposal that he was doing his PhD in bacterial genetics, but he wanted to learn about mammalian viruses and so was writing to me about doing work with retroviruses. I wrote back to him and said, "That's very interesting, but I had just started working on papillomaviruses." And I thought the room for development and learning more was even greater there than with mouse retroviruses, which is what I was working on and what he was proposing to do some post-doctoral research on. Of course, he had never heard of papillomaviruses, so he had to look them up. But he developed a project with papillomaviruses and was able to get an NIH award to come as a postdoctoral fellow to work in my lab, and he actually did the research that he proposed, and it led to our improved understanding of the genetic organization of papillomaviruses. But then, it was clear that John and I got along very well, and it looked like both of us might be able to work together. So, he ended up getting tenure after he had been at NIH for about 10 years. And it's just been an amazing collaboration for me because John knows a lot of things that I don't know, and he thinks that I know some things that he doesn't know. And working together has been terrific, really, because when one of us doesn't want to do anything about something, the other one tends to step in. And so, it's been an amazing partnership that we have had for this time. Dave Johnson: This is really important. One of the reasons we agreed to do this podcast is to provide insight to up-and-coming faculty and fellows about mentoring and partnerships. What is the most important aspect of your partnership with Dr. Schiller? Dr. Doug Lowy: I think treating him as an equal colleague from day one, that probably is important. And then, since I was senior and he was junior, trying to make sure that he got credit when discoveries were made because the default, otherwise, was going to be that it was Doug Lowy who was doing things, whereas it was very clear that John was a key part of this collaboration. Dave Johnson: Now that your relationship is a long-lasting and mature one, how do you make those decisions now? Dr. Doug Lowy: Well, we've just worked together for a long time, and we enjoy talking, and actually, over the last few years, we are collaborating less rather than more. We're still very close colleagues, and we're in the same lab. But since I've been Deputy Director, especially during the last seven and a half years, I've been Acting Director for about three and a half out of the last seven and a half years, and there just isn't enough time to devote to the lab. And it would've been inappropriate for me to have been considered a co-principal investigator with John, who has gone off and done a lot of amazing research, more or less independent of me. Like everything else in this world, it develops, it continues to evolve, but we still are very close colleagues. As Pat was mentioning, this is my first week in several months not being Acting Director, and yesterday, John and I simply reveled in the opportunity to talk informally for 30 minutes without having to look at my watch because I needed to go someplace else. Dave Johnson: I'm glad you've reviewed that. I think a lot of junior faculty and fellows think that being in a leadership position is a cush job, and I'd tell them that it defies the laws of Physics because all poop flows uphill in this setting, and you have to deal with it. Pat Loehrer: I do want to spend some time talking about the NCI and your role there, but talk a little bit about how you have seen and where you envision that vaccines, particularly, HPV and maybe hepatitis vaccine - where you see it's been, and where it's going, and the impact that this potentially has on cancer worldwide? Dr. Doug Lowy: Well, one of the areas that John and I are continuing to work on closely is more research on the HPV vaccines. We noticed, quite a number of years ago, that the HPV vaccine performance was quite different from that of other so-called subunit vaccines. So, this is not an attenuated live vaccine, but instead is a subunit - it's just made up of one protein of the papillomavirus, the protein that gives rise to the outer shell of the virus. And what we noticed in a clinical trial that we were doing with colleagues in the intramural program, but who are medical epidemiologists - they are the leaders of the research, and what was happening was that although everyone was supposed to get three doses, there were some young women who were getting either two doses or one dose, in the trial, and this is in Costa Rica, where historically, cervical cancer has been the number one cancer of women. And it turned out that there was no difference in level of protection whether the women got one dose, two doses, or three doses. And even more surprising was that the antibody levels over the first few years were remarkably stable. And this led John and me to wonder whether it might be possible to get away with just a single vaccine dose. So, a lot of the research that we have been doing with our colleagues over the last few years is to develop stronger evidence that one dose of the vaccine would be sufficient to confer strong protection that's long-lasting. We've now carried out the studies in Costa Rica, with the initial trial to more than 10 years, and the antibody levels continue to be very stable, and the protection does not seem to have waned. Because this was not a pre-specified outcome, it's not enough to change standard of care. So, we and our colleagues are conducting a non-inferiority efficacy trial that is comparing two doses versus one dose of two different FDA-approved vaccines. One, GARDASIL 9, which is the HPV vaccine that's available for sale in the United States. But also Cervarix, which is made by GlaxoSmithKline, it's approved by the FDA, but it's no longer sold in the United States. And we anticipate that the results will read out in another couple of years. And if the results show that one dose and two doses are pretty comparable, we're expecting that this will lead to a worldwide change in recommendations for the HPV vaccine. So, whether you are in a high-income country or a low or middle-income country, that one dose is what will end up being recommended. Pat Loehrer: They could almost completely eradicate this disease, the most common cancer around the world. It's huge. Dr. Doug Lowy: So, Pat, the problem is that although the vaccine was approved 15 years ago, only about 10% of eligible young women in low and middle-income countries have actually been vaccinated up to now. And we think that the logistics and the cost of one dose could really be transformative, especially for those young women. It also would save the United States a great deal of money because needing only one dose would be far less expensive, and the government actually pays for about half of the HPV vaccine that is delivered to teenagers through the Vaccines for Children program.   Dave Johnson: Well, this concludes part one of our interview with Dr. Doug Lowy, Principal Deputy Director of the National Cancer Institute and Chief of the Intramural Laboratory of Cellular Oncology in the Center for Cancer Research. In the second part of this episode, Dr. Lowy will give his insight to vaccine hesitancy in the COVID era and the evolution of accomplishments over the past 50 years working at the National Cancer Institute. We want to thank all of our listeners for tuning in to Oncology, Etc. an ASCO Educational podcast, where we will talk about just about anything and everything. 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