Medicine

You Can't Guide Scientific Discovery: A Lesson from the HPV Vaccine

Highlights from our "Backing Breakthroughs" event on September 5 at Carnegie Institution for Science

Dr. John Schiller and his research partner Dr. Douglas Lowy have prevented an estimated 360,000 cases of cervical cancer and 150,000 related deaths.

Schiller and Lowy are the creators of the vaccine for the Human Papillomavirus (HPV), which causes cervical cancer. They didn’t set out to develop a vaccine but through research flexibility, they developed the life-saving technology — and earned the 2012 National Medal of Technology and Innovation for their efforts.

“When we first started developing this vaccine … we were studying how the virus causes cancer. We weren’t studying vaccines,” Schiller said, describing the unforeseen path to the HPV vaccine at a joint program between Carnegie Institution for Science and the National Science and Technology Medals Foundation.

“We knew nothing about vaccines. We knew nothing about immunology. We nothing about the virion proteins, which became this vaccine,” he added. “We had an idea and we were allowed to pursue this idea without anybody telling us that it wouldn’t work.”

Schiller, now the deputy chief in the Laboratory of Cellular Oncology at the National Cancer Institute (NCI), noted that every researcher’s road to discovery is unique and made possible by “crawling up on the backs of giants.”

For Schiller and Lowy that giant was German scientist Harald zur Hausen — who won the 1983 Nobel Prize for discovering "cervical cancer in humans is caused by certain types of papillomaviruses.”

“I didn’t anticipate this, I could not have anticipated this, but it added so much more interest into the research we were doing at the time,” Schiller said. “If he had not discovered this, we could not have done what we did.”

"We had an idea, and we were allowed to pursue this idea without anybody telling us that it wouldn’t work."


A large series of studies bolstered zur Hausen's findings and further solidified HPV as the "necessary cause" of cervical cancer.

"None of these studies were initiated with the HPV vaccine in mind," he said. "You can't guide discoveries."

“What we discovered is that the vaccine, this pseudovirus, has an amazing ability to bind and infect tumor cells, whereas they don’t infect normal tissue,” Schiller explained. The technology is now being tested for treating other cancers.

The vaccine was also made possible by the partnership — and friendship — between Schiller and Lowy.

“The first thing you need if you want to make great discoveries is to have great mentors and great colleagues,” Schiller said. “I’ve been extremely fortunate to have one guy be both.”

Schiller credits Lowy’s guidance and partnership as a driving force in his career.

“Why do you need good colleagues? Because that’s who you bounce ideas off of,” he said. “… It also helps you separate the good ideas from the majority of ideas, which are bad.”

“I can’t tell you how many times an idea has come to me because I’m talking to somebody, that I’ve never had by myself — except for shaving. I actually have really good ideas while I’m shaving,” Schiller added.

Schiller also discussed the processes that drive scientific breakthroughs with experts Dr. Devaki Bhaya, Dr. John Spiro, and Kei Koizumi.

For Schiller, breakthroughs that led to the HPV vaccine were possible through the National Cancer Institute’s funding mechanism.

“One of the great things about being in the NCI intermural program is basically they give me money for four years to do what I want, and at the end of four years they say ‘what did you do for us during those four years?’” he said. “… If they like what you say they give you stable funding for the next four years.”

“We really have been blessed with the ability … to [pursue] new ideas without having to ask a grant committee whether we can do this or not.”

Schiller noted that without the flexibility to follow where his research led him — often absent in the traditional grant proposal process — he and Lowy would not have found the path to the HPV vaccine.

Koizumi, American Association for the Advancement of Science visiting scholar in science policy, echoed Schiller’s point that scientists should decide which ideas are worth pursuing. Today’s scientific funding mechanism started with Carnegie Institution’s fourth president, Vannevar Bush, based on the proposals of scientific investigators.

“He recommended creating a government-wide effort that supported basic research and applied research — creating the system that we know today,” Koizumi said. “He outlined how the U.S. government should do it, by policies that encourage investigators to come up with their own ideas, sometimes wild and risky ideas, and that federal agencies should support those ideas, with money, tools, and infrastructure.”

"You can start to see science not necessarily as a competitive enterprise, which often it is seen as, but as a collaboration."


Bush’s recommendations also led to the creation of the National Science Foundation.

Bhaya, the current National Science Foundation program director, said funding is only half the battle, the other half is nurturing scientific discovery.

“There is a huge passion for doing science. It’s not something that goes away very easily. It’s there, you have it and you keep trying to do it,” she said.

“One of the things we need to really think about from when you start as a kid to when you are a mature scientist is that we make an ecosystem that allows all of science to flourish,” said Bhaya, who is also a Carnegie Institution staff scientist in the Department of Plant Biology.

In this “ecosystem” she emphasized that “the trees need to talk to each other.”

“A single investigator can push their ideas, their intuitions, but very often that doesn’t work — you’ve got to do it in a group,” Bhaya said. “… [Then] you can start to see science not necessarily as a competitive enterprise, which often it is seen as, but as a collaboration.”

“There are areas where you have to have a biologist maybe talking to a physicist,” she added. “Classically, those have been domains that have been kept separate, by funding agencies, universities, and the rest.”

In research, collaborative efforts can produce great science but blur the lines of who can claim credit. But Spiro, the deputy science director for the Simons Foundation Autism Research Initiative, argued collaboration can amplify research potential for paradigm-shifting results.

“People would rather be part of a big team that hit a home run and really sort of opened up a field, as opposed to being senior author on a small paper that had an extremely high likelihood of not being replicated,” Spiro said.

But a researcher’s mission doesn’t end once a life-saving technology is discovered  — it must make it to market, where people can benefit from the research. For the HPV vaccine, it was a 15-year process from discovery to licensing.

“For these types of public health interventions, getting to the point where they can start doing some good can take a long time, so you have to be in for the long haul,” Schiller said.