University of Wisconsin-Madison Professor Emeritus James Dahlberg received the Bayh-Dole Coalition’s American Innovator Award for his work turning university research into a Human Papillomavirus (HPV) screening device used by over 19 million people.
For Dahlberg, the journey from biochemistry research to a nationwide screening tool started not with a business plan, but with scientific curiosity and a few strands of DNA. Dahlberg’s discovery led to a diagnostic test that has detected more than 623,000 cancers in the last decade alone and launched a decades-long journey of entrepreneurship and invention which has helped make Wisconsin a biomedical hub.
Dahlberg, who served in UW-Madison’s Biochemistry department for 36 years, used his research at the university to create an enzyme and DNA combination capable of identifying virtually any DNA sequence.
A chance discovery
While Dahlberg was a professor at UW-Madison, he stumbled across a unique function of the DNA replication process Polymerase Chain Reaction (PCR), a laboratory tool used to rapidly generate millions or billions of copies of a specific DNA sample.
When inserting triple-stranded DNA into PCR, he noticed an interesting reaction: the PCR enzymes would not only replicate the DNA, but also “cut” the DNA, separating unneeded strands out of the replication sequence. At the time of this discovery, Dahlberg said there were “no enzymes that would cut DNA specifically.”
The discovery allowed researchers to further sequence genomes and conduct screening tests for a range of diseases, including HPV.
Dahlberg’s method of using PCR enzymes to cut triple-stranded DNA was patented by the Wisconsin Alumni Research Foundation (WARF) in the early 1990s. UW-Madison researchers apply for WARF patents when they discover or build material that could be applicable in an industry setting. Typically, these patents are licensed out to companies through the university, and in the early 1990s when Dahlberg’s discovery was patented, WARF only allowed established companies to license their patents.
“[In the] early 1990s, WARF had two policies,” Dahlberg said. “One is that they would not pass or not license discoveries back to the university inventor. The second problem was that even if they did, they wanted cash for license fees, and we certainly couldn't afford that.”
Dahlberg and two fellow professors created the company Third Wave based on his patented research, and with the help of WARF’s newly elected CEO Dick Leazer, his team became the first ever researchers at UW-Madison to bring their discovery to market. Leazer gave the team the rights to their research and bought a stake in the newly-founded company to give them funding.
After applying for federal grants and receiving seed money from private investors, research on how to apply Dahlberg’s discovery could begin in earnest. But becoming a businessman didn’t come naturally to the veteran researcher.
“There are ups and downs in anything,” Dahlberg said. “I mean, times when we thought that our product was so good it could solve all the problems of the world. Then, of course…we started to burn money in a way that we shouldn't [have].”
After hitting hard times, Dahlberg and his team hired a new chief executive officer who consolidated the team’s vision around a singular application: detecting HPV.
HPV is one of the most common skin-to-skin transmitted viral infections in the world, with over 80% of all sexually active men and women estimated to be infected by the virus at least once in their lifetime. While the virus itself is usually minor, and most infections usually do not lead to cancer, certain strains can develop into five different types of cancer.
Third Wave realized they could use the PCR enzyme’s “cutting,” or “cleavage,” activity to probe inside DNA molecules, finding changes in their sequences that would have previously remained undetected.
Using this discovery and a newly directed focus, Dahlberg and his team synthesized “probe” DNA structures to combine with a patient’s existing DNA and see if it would create a cleavable structure, indicative of being HPV positive.
After years of research and development, Third Wave was eventually bought out by the women’s health company Hologic in 2008, marking the start of commercial sales for Dahlberg’s research, which has now been used for more than 19 million screenings.
Looking to the future
While Dahlberg is now retired and occasionally spends time consulting different labs, he warned of a slowdown in medical research if the Trump administration continues cutting research funding.
“I think it’s a tragedy that many investigators have to shut down very productive discoveries and research programs,” Dahlberg said. “If you say the wrong thing, or do the wrong thing, then they can come in and wipe you out.”
Federal agencies have already cut at least $12 million in research funding and over 20 student research positions at UW-Madison.
Dahlberg also advocated for professors being able to commercialize their research, a practice which only started becoming commonplace at UW-Madison after his successful research venture.
