The phage lab has been a center for undergraduate research at Evergreen since Elizabeth (Betty) Kutter and Burt Guttman both came here in 1972, one year after the college opened. From the beginning, it was supported by an NIH grant Betty brought with her, which was followed by an unbroken series of crucial grants from NSF and/or NIH. The early work focused on phage genetics and the transition from host to phage metabolism after infection of E. coli by T4, particularly on the roles of T4′s use of 5-hydroxymethylcytosine (HMdC) in place of cytosine in its DNA, the gradual degradation of the host DNA and the role of T4′s gpAlc in the shutoff of transcription of cytosine-containing DNA. In 1975, we held our first small Evergreen Phage Meeting, which gradually expanded to the biennial Evergreen International Phage Meetings, building on our experiences at the classic Cold Spring Harbor meetings. Through the years, collaborations with Evergreen colleagues and many members of the phage community added new strengths and directions, such as the T4 genome project of the 1980s and 1990s (involving Japanese, German and Russian collaborators), ecologically relevant simulations and a variety of new phages.
We first learned about the therapeutic applications of phage in 1990 when Betty Kutter spent 4 months in the Soviet Union working on T4 transcription regulation and the T4 genome project under an exchange program between the US and USSR Academies of Science and made two brief visits to Tbilisi. As the walls between East and West crumbled, we developed a strong relationship with the Eliava Institute in Tbilisi and the Evergreen meetings expanded to include therapeutic and other phage applications to complement our molecular work. From 1995-1999, one of the first 10 NSF “Collaborative Research at Undergraduate Institutions” $950,000 4-year grants brought in protein biochemist Jim Neitzel, computer scientist Judy Cushing, and outside partner Fred Neidhardt of the University of Michigan and greatly benefitted our resources and molecular explorations. During that period, there were usually 15-20 students in our lab, which was still the only externally funded basic research lab at Evergreen.
In 1999, British faculty member Andrew Brabban significantly impacted phage research at Evergreen. Having worked in both industrial and academic settings, Brabban brought expertise in biotechnology and microbial physiology, especially under anaerobic conditions. We quickly struck up a close working partnership, born of a mutual interest in designing new technologies to help society and in “finding answers to the questions people never ask”. We focused particularly on understanding the infection process under conditions better reflecting those in the natural environment, as well as on interactions between phages of different families during simultaneous infection and the building of cocktails for potential therapeutic applications. In efforts to help clear E. coli O157 out of the guts of livestock, we worked with phages isolated from sheep and cattle (mainly of the T4, ViI and T5 families), collaborating with USDA scientists in College Station, Texas. We also studied many phages targeting Pseudomonas aeruginosa from cystic fibrosis patients and from dog-ear infections, in collaboration with scientists at the Eliava Institute in Tbilisi Jane Burns at Children’s Hospital, Seattle, a local veterinarian and colleagues in France, England and Australia.
From 2009 to 2012, we partnered with faculty biologist Ben Simon. Since then, faculty member/veterinarian Mike Paros has had a parallel phage lab at Evergreen, working first on phage targeting bovine mastitis with some support from the Washington State Dairy Association, and then on phage targeting rumen bacteria. We continue to collaborate in various ways. We also have been collaborating with the Phagebiotics Research Foundation that we started in 1997 on supporting clinical applications of phage.