Basic Science and the Unexpected Path Forward

Recently while my wife (Norma Gilson ’70) and I (Ian Gilson ’70) were strolling along our beloved lakeshore path along Lake Mendota on the University of Wisconsin campus, we passed a marker that brought back memories. Dr. Howard Temin, who walked this path many times during his tenure as a cancer researcher at McArdle Cancer Research Lab, and to whom this path is dedicated, gave a lecture that I attended as a University of Wisconsin undergraduate in a genetics course in 1969. He discussed his discovery of a novel enzyme he called RNA-dependent DNA polymerase. He found this enzyme to be present in tumors of chickens, mice, and cats. It broke the cardinal rule of genetics, which is that DNA makes RNA, which makes protein. The concept of an enzyme which allows RNA to make DNA was revolutionary. He stated that this may be a key to the cause of human cancer. He won a Nobel prize for this work in 1975. As it turns out, he was wrong — the only human cancer ever linked to this enzyme is the rare T-cell leukemia. However, this discovery turned out to be the most important concept I learned in college for the impact on my future medical career. In 1985, I saw my first patients with AIDS. Dr. Temin’s enzyme, now called reverse transcriptase, was detected in lymph nodes of people with AIDS and was produced by a virus initially called HTLV3, later renamed HIV. This virus infected T cells and devastated the immune system of those who carried it, leading to invariably fatal infections and secondary cancers. I was able to refer one of my first AIDS patients to the first clinical trial of a drug that blocked reverse transcriptase — AZT — and after the trial was shown to be successful, I was able to treat patients and extend their lives for a short period of time. Other reverse transcriptase inhibitors followed, with more efficacy and less toxicity, and then protease inhibitors and integrase inhibitors, which, in combination with reverse transcriptase inhibitors, led to highly successful combination therapy with restoration of the immune system and close to normal life expectancy. This was where we were in the late 1990s. But we could see the immense suffering that AIDS was causing in Africa and other developing parts of the world where these drugs were not available. In 2003 the PEPFAR program was created, making these lifesaving drugs available in Africa. In teaching trips to Kenya in 2004 and 2007, I saw some of the first East Africans to receive antiretroviral drugs, and then witnessed the dramatic turnaround in their medical status. In 2008, I became a volunteer speaker at an annual Uganda HIV management conference, which was started by a collaboration between Dr. Frank Graziano, UW clinical immunologist and founder of the UW AIDS program, and Dr. Peter Mugyenyi, whose work at the Uganda Joint Clinical Research Centre was fundamental to the start of the PEPFAR program. Reverse transcriptase inhibitors are still the mainstay of therapy in the western world and their use in the PEPFAR program has saved over 26 million lives in Africa and other developing countries.

So speculation by a Nobel laureate about the implications of his groundbreaking scientific discovery that I learned about in college turned out to be wrong, but it led to the most powerful healing I could do in my subsequent career and the most impactful health intervention in the history of American foreign aid. Sometimes basic science takes us down a path whose destination cannot be imagined at the moment of discovery.