The key to staying safe is to identify risks, mitigate them and prepare—just in case.  This is true for all sorts of hazards, including the threat of biological pathogens, whether naturally occurring or deliberately engineered.

Researchers at the Department of Energy’s Pacific Northwest National Laboratory are working on this problem with the goal of keeping us safer from a host of biothreats, including those that might result from the effects of a warming climate.

In one such project, researchers are seeking to determine whether any of the billions of bacteria in Alaska’s permafrost could pose harm to humans as it melts. This research and similar biodefense projects rely on a novel method developed at PNNL to isolate pathogens in complex samples. 

The multidisciplinary team combined their expertise in microbiology, proteomics, biochemistry and data analytics to create a three-step analytic technique called OmniScreen. 

Unlike conventional analytic methods, OmniScreen allows bacteria to remain alive after being detected and separated from study samples. This enables researchers to go beyond identifying which bacteria are present to evaluating how harmful they might be. 

The first step involves extracting the bacteria. This can result in more than a million different bacteria that need to be analyzed. The second step winnows this huge sample to those that possess traits that make them likely to infect people.

There are only certain ways that bacteria can infect us, such as adhering to our cells or scavenging our cells for something it needs to survive. So, researchers designed color-coded molecular probes that they use to tag bacteria having those traits. 

In the third step, researchers conduct additional analyses on the tagged bacteria to determine if they will infect human cells. Our bodies effectively fend off many of the bacteria we encounter. The goal here is to find those that could have serious effects on human health. This includes flagging sources of a possible pandemic before it starts. 

To this end, researchers expose human gut and lung cells to the tagged bacteria. These genetically modified cells will glow when an inflammation pathway is activated by the tagged bacteria. Watching the cells under a microscope, scientists can see whether the human cells move away to avoid attack. 

Slow defensive reactions are a sign that human cells are at lower risk. Faster reactions, as well as unsuccessful attempts that lead to cell death, are indicators of a pathogen’s lethality. 

Because it takes more than a week to manually analyze the 14,000 microscopy images generated by each experiment, researchers developed a machine learning algorithm to process the images more quickly. With the help of machine learning, they can now determine if a sample has the potential to do harm in as little as 48 hours. 

Understanding the chemical signatures of infection elucidates both how harmful the pathogen may be and the cellular mechanisms responsible for that harm. Scientists can use this knowledge to determine whether a new preventative measure or treatment option is needed and, if so, how to design an effective vaccine or medication.  

Building on this research, scientists are exploring a new technique that allows them to study cell membranes rather than whole human cells, which can be difficult to keep alive for the duration of their research. 

With university collaborators, they are studying toxins that attack cells by breaking through cell membranes. The new research technique involves stripping cell membranes from living cells, exposing them to different bacteria and then applying electric current. Changes in the membrane’s resistance indicate holes are starting to form—signaling the bacteria’s successful attack. 

When it comes to biosecurity, no one knows when or where the next pandemic will occur. Fortunately, scientists at PNNL, along with thousands of like-minded researchers around the world, are working hard to keep us one step ahead by seeking to understand and mitigate the risks.

Steven Ashby, director of Pacific Northwest National Laboratory, writes this column monthly. To read previous Director's Columns, please visit our Director's Column Archive.