Interview Trevor Lithgow

A unique interview with Trevor Lithgow, Director Centre to Impact AMR at Monash University, Melbourne, Australia

Interview by Maarten van Dongen (MvD) on 28th June, 2022

MvD: It is my pleasure to interview you at the occasion of the Special Newsletter on the Centre to Impact AMR. Could you please tell me a bit more about your own background?

In my undergraduate degree I studied Biological Sciences and then I worked for a few years as a research assistant in a biochemistry lab. During that time, I was trying to decide whether or not I wanted to do a PhD. I was the first person in my family to go to university, and so I really had no sense of what a PhD was. To be sure about my decision, I went overseas for six months traveling around Europe, and when I came back from that trip I had made up my mind to do a PhD. I started work looking at urea cycle enzymes and how they get imported into mitochondria. I then took up a long-term fellowship from the Human Frontier Science Program to work with Professor Gottfried (Jeff) Schatz at the Biozentrum in Basel. That postdoctoral time was a highlight of my scientific career. I worked with really great postdocs and PhD students in the Schatz lab. Jeff was a fabulous mentor and work in his lab gave me skills for how to lead a research program. By the time I’d finished my postdoctoral work, I went home with clarity of mind that I wanted to set up a research group.

I have always been fascinated by evolution and I wanted my lab to explore the evolutionary links between bacteria and mitochondria. This became the core business in my new lab at the University of Melbourne. I worked a lot of students in this field and had a lot of fun training those students. Most of my students went on to do postdocs, mostly in completely different areas which I also really liked; the fact that they felt confident enough to take what they’ve learned with me and then apply it to something else that they were personally interested in.

I moved to Monash University 13 years ago with a Federation Fellowship from the Australian Research Council (ARC). The Federation Fellowship supports a whole research program at a very high level, and the ARC liked back then to fund something that was relatively risky. I wanted to establish at Monash the infrastructure that you would need to study bacterial cell biology as a discipline. Thinking about the cell biology of bacterial cells … it meant putting to one side the fact that they’re so small that it’s technically difficult to look at them as cells. Allowing for that but forging on with all the principles and approaches that are applied to every other cell type that cell biologists work on. This molecular-cellular approach to looking at bacterial biology was fully motivated by the impending doom around AMR.

While at Monash I was awarded an NHMRC (National Health and Medical Research Council) Program Grant, to pursue a collaborative research agenda together with Dick Strugnell, (at the University of Melbourne) and Gordon Dougan (at the Wellcome Trust Sanger Institute). The resourcing and the interactivity that the Program delivered inspired us to start to really think about sustainable solutions to AMR.

MvD: What has been the starting point, or the rationale for The Centre to impact AMR?

We started the Centre to impact AMR in February 2020 with the main driver being that there were brilliant people at Monash working on solutions to AMR, but we were each of us located in different faculties and departments around the University. We had no visibility, no forum in which we could come together and talk about our work, or even the clarity of purpose that we could do something of significance collaboratively at Monash. There was a really clear case for a new, transdisciplinary Centre. The business case we made to Monash was to establish the Centre with a talented crew of professional staff who would be the people who would action whatever was needed in order to establish transdisciplinary, collaborative research programs directed at sustainable solutions to the problem of AMR. Monash gave us a 5-year budget for establishment.

The Centre has 26 research leaders who come together to brainstorm and plan in working groups. We have five working groups now, each with a distinct theme. The over-riding idea behind each working group is that you should go along, give your best ideas and discussions, and the Chair of the working groups then passes back a nascent or formed plan of what is needed to the professional staff in the Centre Management Committee. This committee then does the work to bring action into being for the working groups. Examples include creating an AMR Survivors Group of public advocates, establishing the Monash Phage Foundry for production of bacteriophage and phage-derived products as new therapeutics, coalescing R&D operations for antimicrobial testing and surveillance operations as a service to our researchers and our industry partners.

MvD: To what extent is that you’re talking about 26 leaders and five working groups. To what extent is the Centre well just a collection of many different types of scientific research or has it now become a Centre focusing on one solution or in one clear direction?

Now we are two years in I feel like we’re coalescing onto perhaps three or four solutions that we’re driving forwards. We have avoided the solutions of developing new drugs and improving stewardship for drugs. These are crucial actions of course, but many other groups are already active in this space. The raison d’être for the Centre to impact AMR has been to identify and enact solutions that will change the parameters around how and where AMR evolves, so that new drugs will be effective for longer, and so that old drugs can be brought back into more effective use.

MvD: We know there’s a lot of excellent science around the globe and academic publications but the challenge is to translate this into effective solutions. It’s not only scientific work but also developmental work. To what extent is the Centre equipped to make this translation from basic science into practice?

Right now we don’t have the resources to do that. But there is hope. For example, our Centre to Impact AMR is discovering new types of phages by working with the Traditional Owners of lands and water that are understudied environments. We are characterizing the structures of phages to understand the basis for transport stability and shelf-life. We have also done preclinical testing to be sure that a cocktail of active phages can be used as a therapy. Based on all of this fundamental and practical knowledge gain, we have combined forces with clinicians from around the country as the Phage Australia consortium, and have applied for a multimillion-dollar development grant from the Medical Research Future Fund to take this into application for the treatment of otherwise untreatable AMR infections.

MvD: It’s all about collaboration and joining forces. What do you see within the Centre as the critical success factors to effectively collaborate to get all the noses in the same direction and effectively communicate with each other and make people feel seen?

You know, effective in my mind doesn’t just mean good outcomes, but also that each person in the collaboration feels that their work is better by being in the collaboration. From the outset in establishing the Centre to Impact AMR, we have aimed to be completely honest with one another about this.

It sounds philosophical, but it has worked in a practical sense. The leaders in our Centre come from seven different faculties, and most of us had never talked to collaborators across such big discipline distances: I had never talked to a social scientist or anthropologist or professional educator in a context other than listen appreciatively and congratulate them on their successes. It was new, but also fabulous, to build up confidence and success in conversations about work that we could collaborate on, and how we could add value to one another’s research endeavours. For example, a medical sociologist explaining to us, from their point of view, why people won’t or can’t do the things that you would wish them to do in order to work against the problem of AMR. We then have a proper and productive discussion about what sorts of things could a scientist provide, in order that a social scientist could deliver messages that would be listened to by people and where behaviours might actually be changed.

This sort of thing is really rewarding, but it’s hard to do. “How does it work?” – you have to spend enough time to really appreciate what’s going on, and you have to have a very high level of trust, where you just believe that these people will value what you give them but also treat you well in the collaboration.

MvD: Personally, I strongly believe in these soft skills and you have been able to build a sustainable AMR ecosystem. I think that at the interface of different disciplines is where the most interesting things happen. It is very important to have excellent communication with all these different disciplines and the integrative approach, especially when you talk about solutions.

To what extent is the Centre a standalone initiative within Monash, and a standalone initiative with respect to other AMR initiatives in Australia?

Within Monash, the Centre operates independently. We run from our own budget, and our Executive Committee (drawn from the Centre Leaders) determines how we use our cash and personnel resources to best effect.

In terms of other operations in Australia there were (at the time the Centre began) two other centres in Australia, one in the University of Melbourne focussed on antimicrobial stewardship in healthcare settings and one in the University of Queensland focussed on drug development. So, in terms of drug development and in terms of stewardship there were already two really great places with great people doing great things. The unmet need back in 2020 was a Centre that would operate within a OneHealth framework and be focussed on Sustainable solutions: if you want to impact AMR then you have to do more than get new drugs and use them wisely. So, our remit was biological and education-based solutions to a better understanding of how and where AMR evolves, focussed on action: we want to reverse the evolution that makes drug-resistant bacterial populations by enacting solutions that favour drug-sensitive bacterial populations. These solutions include behaviour changes (eg. stopping the unnecessary overuse of antimicrobial chemicals in soaps and detergents), innovation in manufacturing (eg. smart surface coatings that disfavour the growth of drug-resistant bacteria without impacting drug-sensitive bacteria), and so on. The intended nett effect of these actions being to increase the usefulness of existing antibiotics, and to create a scenario where new drugs will have longer time frames of usefulness too.

Since 2020, there have been some further developments in Australia that add to our capacity as a nation to act against AMR. The Cooperative Research Centre for Solving Antimicrobial Resistance in Agribusiness, Food and Environments (CRC-SAAFE), and an Industrial Transformation Research Hub to Combat Antimicrobial Resistance, amongst others. An exciting challenge now is to merge the boundaries of these Centres to deliver a coordinated national approach to AMR.

MvD: Did you consider teaming up with a bigger company, a diagnostics company to collaborate with to be responsible for development and commercialization of this?

No, we haven’t done that yet. There are limited opportunities for Australian research to be picked up for investment. Personally, I feel that the prospects for investment and commercialization will be improved in the next few years as it becomes more clear that there is a path forward to a coordinated national approach to AMR.

MvD: What is the situation with respect to International collaborations for the Centre to Impact AMR?

The Centre to Impact AMR has been proactive in working with partners in the Indo-Pacific region to act, guided by each countries National Action Plan for AMR, to identify regions of overlap and particularly to develop synergy in the actions that we can bring to bear at a regional level. This has been really rewarding work, and Monash University has been hugely supportive of our ambitions. This is also where the AMR Insights Ambassador program has been really great for us with some of our youngest Centre members, Dr. Rupinder Dhamoon and Dr. Sue Nang, serving as regional ambassadors for AMR Insights. As the Centre to Impact AMR works with our regional partners to frame and implement our collaborative action, we deliberately look for early career people (in research and other fields) in those other countries. These are the people with the most skin in the game for enacting solutions to the future problems associated with the rise of AMR across the region.

MvD: So, you are talking about Australia and New Zealand, Oceania, the Eastern part of Asia. Is there other regional activity focused on AMR?

That, already, is a big region! When we talk about the Indo-Pacific region, it sweeps across to us from India, through southern and eastern Asia and right across the many nations in Oceania. Almost every one of the 26 countries in this region has a National Action Plan for AMR in keeping with the World Health Organization framework to understand and work against the impacts of AMR.

MvD: What is the seriousness of the AMR problem in Australia?

Of course, it’s serious everywhere, but I was pleasantly surprised reading the recent Lancet paper by the Antimicrobial Resistance Collaborators: it seems like Australia is the best place you want to live if you’re worried about getting a drug resistant infection! Even though the numbers say that Australia is doing quite well, I think we lucked out in many respects: some good choices that were made at the right time, but also some of the bullets that were dodged by moves of good fortune.

There were choices made generations ago based on microbiologists giving advice to Federal and State government departments about restricting use of antibiotics in agriculture. In other countries, where these choices were not made, antibiotics that should have been medicines for people have been wasted for growth promotion or as prophylactics. There is of course also the good fortune of being an island nation where there’s more of an evolutionary bottleneck for drug resistant bacteria getting over the borders. We can’t let down our guard, nobody can when it comes to AMR.

MvD: Thank you for providing the opportunity to interview you!