This blog is part of the 'Blog a Book project entitled: The Inside Story -- memoirs of the Microbiology Department (University of Otago) from 1950 - 2010. Blogs are usually shown in reverse chronological order (from newest to oldest). For a 'Blog a Book' the posts are changed to be chronologically displayed (from oldest to newest) as one would in reading a book. Click on the building image in the upper left corner of this blog post to navigated to the beginning of the 'The Inside Story'..
John joined the Department in 1975 after completing a postdoc fellowship with Lewis Wannamaker at the University of Minnesota. He brought with him a ‘passion for streptococci’ and a very engaging teaching style. The following are excerpts from his NZMS Oration given in 2005:
"As far as I now recall, my first significant encounter with the “bad” streptococci was when, as a 12-year old living in suburban Melbourne, a series of sore throats culminated in me developing rheumatic fever. I still remember anxious parents, aching limbs, visits to cardiologists - but most of all, those penicillin tablets: twice a day for 10 years they were a recurring reminder that the streptococcus had got the better of me. From a more positive perspective it seemed that, unlike the case for so many of the other youngsters world-wide who succumb to rheumatic fever, for me there had been no apparent residual heart damage. This, I was reminded, was further incentive to adhere to my daily dosing regimen, since it was known that recurrences of rheumatic fever were far more likely to “bite” the heart. Small compensation that was for a teenager who had soon tired of persistently peeing and perspiring penicillin – it just seemed there had to be a better way to keep the streptococcus at bay.
At Melbourne University
Following high school, I had the opportunity to study at Melbourne University and it was there, in the second year of a science degree, that I was strongly influenced by a truly remarkable teacher, Dr Nancy Millis of the Microbiology Department. Nancy de-mystified microbes for me and I quickly developed a keen appreciation for them and for the central role they undoubtedly played in maintaining the health of humans and indeed of planet earth. We all have special individuals (I think of them as “signpost people”) we meet along the way who clearly make a difference to the path we take. For me, Nancy Millis was one such person. Another was Dr Rose Mushin. With the encouragement of Nancy Millis I had decided to major in Microbiology and a defining experience in final year practical classes was the introduction that Rose Mushin gave to us about the concept of utilising bacterial interference as a means of infection prevention.
I decided to study towards an MSc with Dr Mushin, learning some of the tools of the trade of a researcher. My project concerned the bacteriocins of Pseudomonas aeruginosa, termed pyocins (based on their original species epithet, Ps. pyocyanea). My mission was to develop a practical pyocin typing scheme and to apply this in an investigation of the epidemiology of Ps. aeruginosa infections in Melbourne hospital). In my spare time, I developed strategies for purification of several pyocin molecules and to my surprise found some of them to be the tail components of defective bacteriophages.
At Monash University
Armed now with a range of basic laboratory skills and unexpected new self-belief I turned my attention to my nemesis, S. pyogenes. Nobody at Melbourne University had appropriate research programmes for a fledgling student focused entirely upon gaining knowledge of S. pyogenes and of its role in rheumatic fever. Enquiries of the Microbiology Departments of Monash and LaTrobe Universities drew similar responses. However, in the Pathology Department at Monash Professor Ritchie Nairn, who was skilled in the “art” of immunofluorescence microscopy, suggested a PhD project relating to the role of autoimmunity in rheumatic heart disease. I thankfully accepted, nevertheless quietly convinced that it was the role of the streptococcus in the disease process (not the host response) that I wanted to investigate.
Lewis Wannamaker - University of Minnesota
It was time now to undertake a post-doctoral apprenticeship, and from my reading of the streptococcal literature I knew where I must go. Dr Lewis Wannamaker at the University of Minnesota had established a leadership role in the field and indeed he had been instrumental in helping to develop the guidelines for use of penicillin to provide protection against rheumatic fever recurrences. In 1972 he hosted a workshop “Streptococci and Streptococcal Diseases” at the University of Minnesota attended by all of the leading investigators in the field. In his summing up of the week's proceedings Dr Wannamaker commented that “working with the streptococcus is like a love affair, which I guess explains why so many of us find it difficult to give up”. I found that I could relate comfortably to this sentiment and wrote to him asking if he (for me the “King of the Streptococci”) would consider allowing me work with him, looking for an alternative to penicillin for rheumatic fever prophylaxis. Three heady years of complete research immersion followed and Lewis (signpost person No 3) was generous in his encouragement of me to seek an anti-S. pyogenes BLIS, at the same time cautioning that what the streptococcus really needed was understanding – not extermination. Before leaving Minnesota I wrote (together with Lewis and Adnan Dajani) the first major review in the field of bacteriocins of gram-positive bacteria and upon purifying streptococcin A-FF22 predicted it may belong to the same family as nisin, the best-known and most widely-applied of all the bacteriocins of gram-positive bacteria.
A real job - University of Otago
Now the need was to find a “real” job and although the homing instinct was strong there appeared to be no appropriate job for me in Melbourne at that time. There was one at the University of Otago however, and that seemed close enough to serve as a temporary stepping stone for the inevitable return to Melbourne when the right opportunity arose. The job was mine and I suspect that my PhD supervisor Roy McGiven, a kiwi who had just returned to New Zealand to head the Pathology Department at the Christchurch Clinical School, must have made some helpful recommendations about me to Professor John Miles, then head of the Microbiology Department at Otago.
At this time (1975) the Microbiology Department was in the midst of a substantial growth spurt, having just moved into expansive new quarters and mine was just one of a cluster of new appointments. The life of a young academic at Otago was great - teaching loads were light, research funding was abundant and it appeared relatively uncomplicated to obtain and manage, there was time for reflection and my new colleagues were very supportive. Spirits were high and Dunedin seemed to be a great place to raise a family. Buoyed by this, my wife and I set about raising four sons.
Bacteriocin - chain gang
However, the core agenda for me was still to find a way to tame the streptococcus and it appeared that interest in rheumatic fever in New Zealand was high, since Maori and Pacific Islanders are particularly prone to this disease. Two approaches were taken to finding an antagonist of S. pyogenes. While in Minnesota, I had met many members of an international streptococcal club of sorts, named the Lancefield Society in honour of that venerable lady of streptococcal classification Rebecca Lancefield. I wrote to many colleagues in the club (sometimes known as the “chain gang”) asking that they send me their favourite streptococci so that I might test them for bacteriocins. The response was enthusiastic and we set about systematically screening them against a set of nine standard indicator strains according to a very simple deferred antagonism method similar to the pyocin typing method that I had devised years previously for Ps. aeruginosa. When this bacteriocin production (P) –typing was combined with testing of the streptococci for their sensitivity to a panel of nine different bacteriocin-producing strains (S-typing) it was referred to as bacteriocin “fingerprinting”. Although now probably considered quaintly low-tech and intrinsically simple this procedure has survived as the preliminary screen for all candidate bacteriocinogenic strains entering my laboratory. It soon became clear that most (if not all) streptococci produce bacteriocins of some type and over the succeeding years dozens of post-grads, post-docs and technical support staff have adopted inhibitory streptococci (or sometimes their staphylococcal and lactococcal cousins) and been charged with responsibility for assessing the biochemical and/or genetic basis of their antagonistic behaviour. What transpired was the (sometimes) systematic discovery and categorization of a remarkably heterogeneous array of proteinaceous inhibitory agents, ranging from nisin-like post-translationally modified (the lantibiotics) or non-modified small peptides to larger proteins, some of them muralytic and others having unusual circular conformations. Follow-up reviews have highlighted the profusion and variety of these molecules: streptococci, especially those of the species uberis, mutans and salivarius appear to have been particularly inventive and acquisitive of bacteriocin loci. Recently, we have discovered that S. salivarius utilise very large plasmids as transmissible genetic receptacles for these loci.
The second approach to identifying a S. pyogenes antagonist came in the form of a 6-year prospective study of one-hundred 5-year old Dunedin schoolchildren. The aim was to regularly document the composition of the childrens’ oral microflora throughout the course of the study and in particular to note if and when each child acquired S. pyogenes. The striking outcome was that many of those children who experienced relatively few S. pyogenes acquisitions had large populations of BLIS-producing S. salivarius on their tongues, especially of the P-type profile known as 677. These strains were shown to produce salivaricin A, a lantibiotic inhibitory in vitro to most S. pyogenes. This was very promising, because S. salivarius has had an almost blemish-free record in its association with humans – indeed it is the most common bacterium found in the human mouth and its closest relative is the copiously consumed dairy species, S. thermophilus.
So, things were looking good for S. salivarius as the prime candidate for a bacterial interference approach to the prevention of S. pyogenes infection and it got even better when we discovered a few strains (including S. salivarius K12) that produced in addition to salivaricin A a second lantibiotic (salivaricin B) that appeared to kill all tested S. pyogenes strains, with no sign of any resistance development. It was about now that John Scandrett (signpost person No 4), then director of the University’s Commercial Office, intervened. John quickly realized that I was quite naïve about the practical realities of product development and advised that a patent be put in place on salivaricin B. That done, he arranged for a meeting with the late Howard Patterson, an entrepreneur who at that time had masterminded the funding of several fledgling biotech companies in Dunedin. What followed over the next weeks is still a bit of a blur, but the outcome was formation of BLIS Technologies Ltd in August 2000. Within a short time a CEO (Kelvin Moffatt), a Scientific Director (Chris Chilcott) and a Board of Directors were appointed and the company was listed on the NZ Stock Exchange in July 2001.
As a result of their efforts the first product BLIS K12 Throat Guard appeared on the shelves of pharmacies in early 2002. Several more products have followed and overseas sales are steadily increasing. Further tests are planned to simplify the colonization protocol (powder, lozenge and chewing gum formats have already been developed for different applications) and prospective trials are planned (some back in Australia) to further document the efficacy of this world-first bacterial interference approach to the reduction of streptococcal disease. I feel extremely privileged to have been able to follow my quest for such a long time. My parents, family, colleagues, students and staff, as well as the funding agencies have made it all possible.
May the BLIS be with you all.
60 Minutes programme produced by Brent Fraser - John Tagg and BLIS
While Tagg couldn't be more serious about his subject, when the lecture room doors close he admits that sometimes the clown in him comes out to ease the path to learning. Tagg discovered Microbiology by accident when he signed on for a paper just because it fitted a gap in his timetable. He was inspired by his tutor, Nancy Millis, "whose lecturing style was off-beat, candid, natural and entertaining".
"I attribute a lot of my enthusiasm for Microbiology and my teaching style to her. Although I started in research, the more I taught the more I enjoyed it. And the more I grew in confidence the more my teaching style began to mimic that of my old professor.".
Many students have benefited from Tagg's offbeat approach. "The point of a lecture is not the communication of facts. That's what libraries are for. It's an opportunity to motivate. And if I'm not having fun in a lecture it's probably not working for the students either."
An example of his teaching style can be seen in this TEDxDunedin video:
Each summer, Otago opens its doors to senior high school students for Hands-On Science: a week of field exercises, lab testing, and practical learning aimed at encouraging talented young New Zealanders to consider a career in Science. The popular programme celebrated its 25th anniversary year in 2014. John Tagg, who has been involved with the programme since the beginning, was one of the principle organisers of the event. He was most happy when during the ‘Hands on Science’ sessions he would lead a bevy of students down some path of discovery much like the pied piper of Hamelin.
A gallery of lab photos
John was a very active member of the NZ Microbiological Society (NZMS) and was president from 1994 - 1996. He also contributed to the organization of several international scientific meetings. He has a keen interest in the history of microbiology in New Zealand and has been instrumental in providing some of the archival material used in this book.
Below are some photos from the 2005 meeting of the Microbiological Society at which John gave the Microbiology Oration with which this chapter began.