Parents naturally try to shelter their children from harm. As co-inventor of the first human papilloma virus (HPV) or “cancer” vaccine, C. Richard Schlegel, MD/PhD ’75, a father of three, unwittingly took his paternal drive to new heights. When the Food and Drug Administration approved the HPV vaccine, Gardasil, in 2006, Dr. Schlegel not only contributed to the prevention of a disease that annually kills a quarter of a million women worldwide but also protected his loved ones.
“My two daughters, Jennifer and Kimberly, both got the full course of HPV vaccinations,” says the chair and professor of pathology at Georgetown University. “There often aren’t many opportunities when a scientist can see concrete applications of his or her research. I was fortunate to be working on the right virus at the right time. The unexpected outcome is that it can protect our daughters, granddaughters, and grandsons from cancer.”
More than 40 of the some 150 strains of HPV are spread via sexual activity. Some of these viruses cause benign genital warts, while other high-risk strains account for almost all cervical cancers in women, as well as the majority of anal and a growing number of oral cancers in men. One of the most common sexually transmitted diseases, HPV will infect as many as 80 percent of Americans. For 20 years, Dr. Schlegel and his research team studied HPVs and their role in cancer. Their findings led to the breakthrough vaccine and subsequent development of Gardasil, manufactured by Merck. The original formulation blocks two strains of the virus that cause up to 75 percent of cervical cancer cases and two others that lead to about 50 percent of genital warts. Merck plans to unveil a next-generation vaccine that will protect against 9 HPV strains: 7 high-risk and 2 low-risk varieties.In October, the Centers for Disease Control (CDC) and Prevention’s Advisory Committee on Immunization Practices endorsed the routine use of the HPV vaccine for boys, ages 11 and 12. It also suggested that males, 13 to 21, be inoculated if they missed the initial vaccination. This most recent announcement follows the federal panel’s recommendation made six years ago that girls and young women, between the ages of 11 to 26, be immunized – a suggestion that quickly sparked controversy on both moral and political grounds. Most notably: some opponents believe that preventing HPV infection might actually encourage girls to engage in or increase their sexual activity. And while vying for the Republican presidential candidacy last fall, Gov. Rick Perry of Texas came under fire for proposing a mandate that girls in the Lone Star State be vaccinated.
“I don’t understand the rationale about the vaccine promoting promiscuity as there isn’t any evidence to support it,” says Dr. Schlegel. “The social climate could change, however, with the recent recommendation. If boys join girls in being inoculated, the HPV vaccine may gain more credibility as an effective way to prevent an infection that can cause a variety of cancers.”
The Accidental Scientist
An Internet search a few years ago led Dr. Schlegel to his very first mentor: high school biology teacher Wayne Moyer. “He taught an experimental biology course during an exciting era in molecular biology: scientists were just figuring out how RNA made proteins,” remarks Dr. Schlegel, who grew up in East Brunswick, New Jersey. “I tracked him down to thank him for inspiring me to go into biology and then medicine.”
After graduating from Rutgers University in 1968, Dr. Schlegel came to Northwestern. The medical school’s strong clinical reputation appealed to him as he had planned on becoming a pediatrician. Then after his first year, a summer stint in a microbiology lab at the medical school changed everything. He discovered a passion for research and promptly applied for the combined MD/PhD program. And he also met his future wife, Susan Banks-Schlegel, PhD ’73, who was a graduate student in microbiology.
In 1975 the couple moved to Boston, where Dr. Schlegel completed a residency and postdoctoral fellowship in pathology at Harvard. Following his specialty training, both Dr. Schlegel and his wife found positions at the National Institutes of Health (NIH). There in the National Cancer Institute’s Laboratory of Molecular Biology in the early ’80s, Dr. Schlegel launched the work that would lead to the HPV vaccine. Interested in how viruses alter normal cellular behavior and induce tumors, the young investigator began studying a cow papilloma virus for its rapid cell transforming system. At first Dr. Schlegel didn’t think his research would yield much clinical benefit until a German research team showed a definitive cause-and-effect link between HPV and cervical cancer. Dr. Schlegel soon switched to studying HPV oncoproteins (E5, E6, and E7). He says, “That discovery committed me to the field forever.”
Creating the Vaccine
A biologist at heart, Dr. Schlegel met immunologist A. Bennett Jenson, MD, a Georgetown University faculty member, in 1988. What began as a casual chat about defining different types of neutralizing protein properties of the human papilloma virus eventually resulted in a serious conversation about creating proteins in the laboratory that could provide protection against HPV – in essence, an effective vaccine. The two, along with postdoctoral student Shin-je Ghim, PhD, decided to fuse their efforts. Their collaboration began slowly while Dr. Schlegel was at the NIH and ramped up significantly when he joined Georgetown in 1990.
“I entered the field of immunology kicking and screaming as our areas of expertise were so different. Yet I was comfortable with what we were doing because of Bennett’s experience,” recalls Dr. Schlegel. “Since the virus had been found to cause a human cancer, it was obvious to us that a vaccine was the route to go – if we could do it.”
The collaborators worked through the usual hits and misses of drug discovery. Overcoming the challenge of making proteins with the right shape and properties proved to be exceedingly difficult but not impossible. In 1995 Dr. Schlegel and his colleagues published their findings in the Proceedings of the National Academy of Sciences. They showed in an immunized canine model that their novel vaccine provided a 100 percent protection against a mucosal papilloma virus like that seen in cervical cancer. By achieving this major milestone, the investigators had shown they could, indeed, do it.
Collaborating with an international group of investigators and supported, in part, by a $3.5 million grant from the Bill and Melinda Gates Foundation, Dr. Schlegel is now working on an inexpensive, portable version of the vaccine for use in the developing world. Researchers hope to reduce the current going cost of the HPV vaccination – which requires three shots – by 10-fold. Currently some 80 percent of deaths from cervical cancer occur in countries where women do not have easy access to routine PAP smears and/or follow-up HPV care.
The recipient of Georgetown’s 2011 Patrick Healy Award for his contributions to science and medicine, Dr. Schlegel still marvels that he had a hand in creating a vaccine that can save lives around the world. He credits the unforeseen twists and turns in his career that allowed him to become a key player in this major discovery.
“It was really a little bit of serendipity,” says a very humble Dr. Schlegel. “A lot of things just came together all at once that helped us to achieve our ultimate goal.”