The Shots Felt Around the World

The Shots Felt Around the World

How two Bethesda scientists' collaboration led to the HPV vaccine against cervical cancer

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It was a jump up-and-down, pop-the-champagne, high-five kind of moment. Drs. Douglas Lowy and John Schiller, two Bethesda residents working at the National Cancer Institute, had overcome one of the main obstacles in the development of a vaccine against cervical cancer. Their work would lead to the immunization of millions of schoolgirls and represent a major step in eradicating a leading cause of cancer deaths among women worldwide.

But Lowy and Schiller couldn’t know that at the time, so they weren’t ready to celebrate just yet.

“It was quite promising, but there were a bunch of different places where this could have failed,” Schiller recalls nearly 20 years later as he sits with his partner in Lowy’s window-lined office at the National Institutes of Health in Bethesda.

Drug manufacturers were skeptical that a vaccine could successfully target human papillomavirus, or HPV, the sexually transmitted infection that causes virtually all cervical cancers. Lowy and Schiller’s team had shown, however, that “virus-like particles” generated by an HPV protein triggered a strong immune response in the laboratory.

Could inoculating girls with the virus-like particles protect them against HPV?

As it happened, it could.

Last year, Lowy and Schiller won the 2011 Albert B. Sabin Gold Medal Award for their HPV research. “Millions of lives will be positively affected by Lowy and Schiller’s dedication in developing the world’s first vaccines against cervical cancer,” Sabin Vaccine Institute President Dr. Peter Hotez said in announcing their selection.

The story of how they did so is one of timing, a bit of genius and the result of an unusual collaboration between two scientists.

In the mid-1800s, an Italian physician observed that cervical cancer was common among prostitutes but rare in nuns, suggesting that sexual transmission might play a role in the disease.

Then, in the 1930s, two American scientists found that a papillomavirus induced warts in rabbits that could progress to a type of skin cancer. However, since genital warts in humans almost never progress to cancer, HPV was pretty much ruled out as a cause of cervical cancer.

By the early ’80s, recombinant DNA technology and molecular cloning had enabled scientists to figure out that there were many different types of HPV. The types that caused genital warts didn’t cause cancer, and vice versa.

Around that same time, a German virologist named Harald zur Hausen came to NIH to speak about his research showing that, contrary to earlier findings, HPV did indeed cause cervical cancer.

The scientific community was slow to accept zur Hausen’s findings, though the virologist would go on to win the 2008 Nobel Prize in Physiology or Medicine for his discovery.

Previous population-based studies suggested that the herpes simplex virus caused the disease. Try as he might, zur Hausen couldn’t find the herpes virus in most cervical cancer biopsies, but he found HPV in virtually all of them.

Schiller, who had recently come to Bethesda as a postdoctoral fellow to work with Lowy on tumor virology, was in the NIH audience that day. After listening to zur Hausen, “my eyes were sparkling,” Schiller says.

“There was at least a five-year period when there were believers and skeptics,” Lowy says. “We were in the camp of believers, because we thought that the molecular evidence was very strong.”

By the late 1980s, he says, “it became crystal clear that HPV infection was a necessary cause of cervical cancer.”

All that remained was to find a vaccine.

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