It was my honor to nominate Patricia C. Giclas for the Pioneering Women in Complement award and I was delighted to hear she was chosen as an awardee with such distinguished company as Dr. Gigli and Dr. Janatova. When Dr. Giclas learned of her nomination her son told me that it brought a smile to her face and she and her husband Hank started to plan for her return to ICW in 2020, but that trip was not to be. Instead of her presence, this article stands as a poor substitute. Her tales of the early use of complement work in the US were clearly lively and sometime continuous. It was my privilege to hear Dr. Giclas tell the tails but I cannot relate her stories with the candor and humor we all know so well.
When I think of how Dr. Giclas’ impacted complement starting with her pivotal research (we would be well served to revisit her work in light of today’s pandemic) to her early understanding of the importance of quality, accurate complement testing in the diagnosis of human diseases (something that has gained traction only in recent year), I am impressed anew with her pioneering spirit. Dr. Giclas started her academic career at the University of Arizona in 1956 where she studied physics and mathematics. Before finishing that degree Dr. Giclas made the decision to put her family first and stepped away from her schooling for 10 years to raise her two sons. When they started school, Dr. Giclas herself returned to her studies, finishing her BS in Biology with high honors at New Mexico Institute of Mining and Technology. From there Dr. Giclas moved to Tucson where she completed her PhD in Molecular Biology at the University of Arizona. It was during her graduate studies that Dr. Giclas started her work in complement immunobiology. Then she was off to the Scripps Clinic and Research Foundation where she worked from 1975 to 1977 in one of the nation’s more dynamic and active complement research programs. In 1977, Dr. Giclas made the move to Colorado to continue her work in complement at what was then known as National Jewish Medical and Research Center, following her mentor Dr. Peter Hansen. It was at National Jewish Health that she built her career. Eventually she and Hank bought a house in the inviting foothills of the Rocky Mountains but in her early years in complement research she demonstrated her tenacity for the field by living in Denver with one son while Hank’s work kept him and their other son in New Mexico.
When I look back as Dr. Giclas’s publications, I am struck by how much of her early work has bearing on the current pandemic and ‘new’ questions arising from the advent of complement therapeutics. It reminds me again how deep her ‘unpublished’ knowledge of the complement system went and how lucky I am to have her as a mentor. Dr. Giclas’s PhD work and early publications focused on the activation of complement by subcellular membranes, particularly the membranes of the cardiac mitochondria. She also outlined several mechanisms of activation of complement that are outside our textbook thinking about complement. Specifically, in her early work she helped define an IgG independent activation of complement by monosodium urate crystals, as well as activation of complement by a specific strain of Western Red Cedar. The latter was a help in figuring out why a specific group of loggers and sawmill workers were coming down with asthma. This work was a prelude to her important role in complement diagnostics and therapeutics. Dr. Giclas adeptly utilized studies of rabbit complement to broaden our understanding of innate immunology, elucidating the acute phase response of C3 and C5, as well as work on the interaction of complement and plasma kallikrein. But an area of work that was met with derision at the time but now o is most salient to the current pandemic is Dr. Giclas’ work in complement and the lung. In the 1970’s and early 1980’s her grant applications to NIH to work on the lung and complement were given poor scores. She shared with me that she often received comments like ‘there is no complement in the lung so there is no merit to the application’. We know now that that is far from the truth and have seen strong evidence for a role of complement in the dramatic effects of COVID-19 where complement therapeutics show promise. We may all do well to re-read her work elucidating complement and the lung in general and the role of this complement cascade in the acute respiratory distress syndrome, specifically.
Dr. Giclas was not one to walk away from her belief in the role of complement because some reviewers could not see what she clearly saw. She stayed in the field, using her strong skill set and her aptitude for complement analysis to answer the queries of physicians and patients. At the time complement testing was not at all common in the US and where it was available it was highly limited. Dr. Giclas soon recognized there were more patients suffering from undiagnosed complement disorders than had been previously recognized, so she put her expertise to work to develop reliable diagnostic testing. She soon proved not only was she a pioneer in complement but also was a pioneer in clinical immunology testing. She quickly built her reputation for a deep understanding of the clinical effects of complement activation, authoring numerous chapters and books on complement testing. This too was pioneering work, as we now see complement testing in some form in almost all large clinical testing laboratories. Dr. Giclas joined with her colleagues from across the globe to start the efforts that are now the ICS Committee for the Standardization and Quality Assessment of Complement Measurements.
This increase in testing is driven by not only the increase in awareness of the role of complement in human disease, but also by the advent of biologic-based, novel new drugs, an area again where Dr. Giclas was a pioneer. In the 1990’s Dr. Giclas was part of the team who determined that the new class of therapeutics based on small interfering RNA could dramatically activate complement through the alternative pathway after unexplained and dramatic effects were seen in pre-clinical trials. This launched her work in Investigational New Drug development under the US FDA drug development requirements. This preceded the advent of the first complement specific drug, but set up the framework for this regulated work and added to her deep understanding of the potential clinical consequences of unwanted complement activation.
While I could not do justice to her stories, I hope I was able to share enough of her work to paint the picture of Dr. Patricia C. Giclas as a tenacious, complementologist who didn’t take ‘No’ for an answer. She paved her own path, balancing her career and her family in ways that would have been too hard for some. She moved research, diagnostics and therapeutics forward for the benefit of so many.