Hi Simon,

Apologies for the extremely delayed response — I haven't checked back on this post in a long time. I stopped actively working on this project when I ran into hard funding constraints, but a friend recently mentioned it which prompted me to check back in.

Thanks so much for engaging with this, it's genuinely exciting to get feedback from the NAO team itself.

i) Sample access and permits:

You raise a fair point about permits, but I think funding is the much bigger hurdle. The technical and regulatory pathways largely exist already. The Institute of Environmental Science and Research (ESR, NZ's Crown Research Institute responsible for public health surveillance) has demonstrated wastewater surveillance is operationally feasible through their COVID-19 work, and composite sampling protocols are well-established. The real bottleneck is securing sustained government funding for what would be framed as pandemic preparedness infrastructure.

I had preliminary conversations with both ESR and the National Public Health Service in Te Waipounamu (the South Island arm of NZ's public health system) about this proposal. Both were genuinely interested in the concept and confirmed the technical merit, but the response was consistently the same: there's currently no appetite or budget for new pandemic preparedness initiatives, and in fact the system is moving in the opposite direction post-COVID. The Regional Chief Health Protection Officer I spoke with offered to keep it as an idea for when things free up and potentially help present it to senior leaders for a pilot. As this is an election year, government priorities could change.

ESR's response was similar. They didn't see NZ government funding being available anytime soon and felt the cost-benefit would need to improve to justify the effort and expense. As of October 2024, they were about to start some Oxford Nanopore sequencing on aircraft samples, hoping the longer read lengths would improve pathogen identification, though they noted the required sequencing depth was still a major open question. My original cost estimates were all based on Illumina, so I'm thinking about if it's worthwhile to redo them with Nanopore as a comparison to capture the different capability tradeoffs (longer reads, direct RNA sequencing). I could also revise the cost model to assume use of existing lab space and sequencer infrastructure rather than purchasing new equipment, which should bring overall costs down significantly.

Would be keen to hear if NAO has lessons learned from other jurisdictions on how they've secured initial funding, particularly in environments where the political appetite for pandemic preparedness has waned. I'm interested in your view on Illumina vs Nanopore tradeoffs for this specific application. The Nanopore advantages for novel pathogen identification seem compelling, but I'm uncertain how the depth and per-base cost comparisons play out in practice.

ii) What a pilot would look like:

• Sequencing approach: Given your point about not being able to purchase 1.5B flow cells individually, this is where my original proposal needs revision. Would the most realistic approach be either: (a) using a smaller sequencer platform that matches pilot-scale throughput, or (b) batching multiple days of samples to fill a full 25B NovaSeq X flow cell, accepting the detection time delay? Or is there a third option I'm missing?
• Location: ESR would be the natural institutional partner given their existing wastewater sequencing experience from COVID-19. They have sites in Auckland (Mount Albert), Wellington/Porirua, and Christchurch. I'm not sure which sites currently have the relevant sequencing infrastructure, but ideally the pilot would use whichever site is closest to the sample source to minimise transport delay. If sequencing has to happen in Wellington while samples come from Auckland, cold-chain overnight shipping would add maybe a day to the pipeline. I'd be interested in your view on whether that delay materially undermines the early-detection value, or whether it's negligible compared to the total library prep, sequencing, and bioinformatics turnaround.

Would love to hear NAO's perspective on what sequencing platforms and operational models have worked best for early-stage wastewater metagenomics programs elsewhere, particularly for small pilots facing the unit economics challenges you've highlighted.

Thanks again for the feedback. This is exactly the kind of reality check the proposal needed. I'm still very interested in the space and hope to see progress on metagenomic surveillance in NZ eventually.

Thank you Karen. I have been in contact with people at Health New Zealand and at ESR but unfortunately, due to the current administration's cuts to the budget they think it is unlikely to be implemented anytime soon. Feedback from one scientist at ESR was that the sequencing cost was still too high, although perhaps he would change his mind when the costs are compared to the estimated damages.
In regard to industrial animal agriculture, this may be a problem in New Zealand that I am ignorant of, but it seems most likely the pathogen would emerge internationally rather than locally, hence my focus on border detection, although you make a good point and I'm glad that area is not being completely neglected.

Thanks Swan. I have thought about doing that although I haven't written a policy brief before. It seems like this model of screening airports would work best in island countries such as Australia, and I could probably adapt this report for that context. My greatest uncertainty is in the estimate for cost savings as this depends on predicting the frequency and severity of future pandemics. Do you have any feedback on this area?