CPR: Contamination, Prevention, Resilience

Life Finds a Way.

But in mammalian cell culture, its not always the life we want.

Every biology lab deals with bacterial or fungal contamination at some point. Most lab teams know this, but few organizations talk about it openly and effectively reward the due diligence required to mitigate its risk.

I’ve seen contamination halt operations at small and large scales. A variety of organisms from classic E. coli to various strains of Bacillus. Oddly enough, the conversations around what to do were often more difficult than how to handle the contamination itself. Oftentimes the obvious solution to lab personnel is to discard every open reagent, every active culture, every exposed experiment plate, and sanitize or sterilize every piece of equipment that remains. But that so-called “nuclear option” can be an extremely bitter pill for stakeholders to swallow. They needed the data in those assay plates yesterday, surely there is something to salvage for that [figure/grant/meeting].

Story Time: The little classifier that could

In a previous organization, we had a wonderful annual event called ‘Hack Week.’ It presented as an opportunity for scientists, both wet and dry lab, to pause what they were working on to form new teams and dedicate themselves entirely to a new problem. Having dealt with blooms of contamination that resulted in >100k lost in consumables and labor (sometimes in a single event), we proposed a detection and reporting tool that leveraged our AI-powered image analysis pipeline. I was delighted by the interest and the speed at which we were able to form a small team consisting of myself, a senior discovery biologist, a data scientist, a bioinformatics scientist, and the lead of QC analytics team for our high throughput platform. It was a fun week of playing startup from a small, isolated fishbowl style conference room where we devised the strategy and even held a contest to help crowd source data annotation from a wider audience (I started strong but ultimately, happily lost that contest).

At the end of the week, we had a method that could produce a per-well probability score for contamination for in each assay plate in a production experiment with over 90% accuracy in our annotated test data. The Analytics team decided to take this project and make it a part of their QC pipeline. A clear success for our hack week, but still more road to travel and obstacles to clear before our AI-powered sentinel will be fully online.

We did this without any fanfare. We quietly continued the work until it became clear that the prioritization did not exceed the obstacles to implementation. The project, despite initial results and excitement from the lab and analytics teams, was quietly moved from second priority to third, to fourth, and to the dreaded, undefined ‘paused’ state. It was exactly this lack of attention that led to this project’s untimely “pause” from which it was unlikely to return.

I noticed that stakeholders only gave the problem attention when it was on our proverbial doorstep. It was a short demonstration I, as well as others, have seen before: that attention follows acute pain rather than chronic risk. If we weren’t actively discarding experiments worth 10’s of thousands in consumables alone and/or missing critical deadlines, then efforts to de-risk future spread of contamination, like our sentinel program, are silently deprioritized.

That silence is where the problem grows.

Inside the company, any discussion of contamination often stayed within the lab team, operations group, and a small circle of scientific stakeholders. As you move further from direct lab execution, the mentions grow understandably quieter. Investors, collaborators, and partners are very unlikely to hear about it unless a critical milestone or deliverable is significantly and openly impacted.

That silence can create the wrong culture around a very normal risk. (see what I did there?)

In large-scale cell-based screening, contamination risk increases with throughput, handling complexity, shared instrumentation, and scheduling pressure. Teams move plates, maintain incubators, operate liquid handlers, image cells, change media, dose compounds, and manage waste. Every touchpoint adds risk.

 CPR: Contamination-Prevention-Resilience

Contamination: We should remove the stigma from the discussion. When teams fear blame, they delay escalation, soften documentation, or treat contamination as a private lab failure rather than an operational risk. That makes the problem harder to contain and harder to learn from. Avoiding or minimizing discussions of contamination risk, especially during assay hand off or scale up, leaves a large elephant in the middle of your meeting room.

In order to avoid the deprioritization of de-risking practices, it behooves teams to address that elephant early. Before an event can cost unnecessary time and resources to contain.

Prevention: Most scientists and operators already know what good sterile practice looks like. The drift happens when timelines and incentives reward speed while treating biosafety as background work. Teams rationalize shortcuts and delays in routine cleaning when stakeholder timelines do not account for maintenance and budgets do not allow for redundancy.

“I washed my hands.”

“I turned on the UV.”

“No one had time to help me clean.”

Those responses become predictable when teams delay deep cleaning for hoods, incubators, water baths, liquid handlers, and shared equipment because the next experiment always feels more urgent. But the organizational discipline, or due diligence, can free operations teams and stakeholders from the stress of waiting and worrying about that next soil-born bacteria multiplying within the confines of the spinner plate that lives inside TC incubator #7.

Resilience: Prevention costs time and money, but can ultimately save both. It requires more PPE, scheduled downtime, redundant equipment, and clear ownership for routine decontamination. All of these resources are easy to defer when nothing is on fire. Unfortunately, there is often an ember or two under the surface (see ref). The gap between immediate attention to mitigate acute pain and that needed to minimize that chronic risk is exactly the gap our sentinel project fell into.

The tool was not conceived or built to manage a single crisis. It was meant to ensure that low, background-level risk never spreads enough to demand active budget or consideration. But without the acute, attention grabbing, reality of an ongoing contamination event, the organizational attention needed to provide resourcing for de-risking tools simply dried up. A risk assessment, done early and revisited on a schedule instead of after an incident, is one of the few tools that keeps prevention work alive when it isn't urgent. It puts a number and an owner on things that would otherwise just live in a lab team's institutional memory and ultimately near the very bottom of its to-do list. It also gives space to address contamination risk before it becomes a problem, removing any stigma that prevents teams from developing the tools to monitor, mitigate, and minimize the impact of an event.

Contamination will always be part of cell-based biology. Strong platforms acknowledge that reality early, communicate risk clearly, and reward the resilience required to keep the pipeline moving.

An ounce of prevention still beats a sudden stop.