Letter From the Editor: Infection, Identification and Intervention

by Stanley Maloy, Ph.D.
Microcosm Editor-in-Chief

The COVID-19 pandemic has taught us that human health depends on proactive planning rather than trying to rapidly develop and disseminate public health interventions in response to a new infectious disease. This preparation relies on basic and applied microbiology research, well-equipped and staffed clinical laboratories, and innovative life sciences companies.

Effectively responding to an infection requires a quick and accurate way to identify whether a person is infected with a particular pathogen.
Before we understood the microbial nature of infectious disease, diagnoses were based solely on a person's symptoms. Because so many different infections share common symptoms, this approach often led to lumping many disparate diseases together. For example, typhus was often mistakenly identified as typhoid fever. Once it became possible to culture bacteria, the culprit could sometimes be identified in a clinical laboratory. Although much better than simply monitoring symptoms, the difficulty of culturing many bacteria, viruses and eukaryotic microbes often makes this approach challenging. Similar arguments can be made for basic microscopy and biochemical tests.

The advent of nucleic acid-based diagnostics, immunological assays and microfluidics dramatically changed our ability to rapidly identify potential pathogens with high levels of sensitivity.
And, as described in the article "Tracking Pathogens via Next Generation Sequencing," new genomic and metagenomic approaches have provided an exquisite ability to distinguish different strains of closely related pathogens, facilitating our ability to track where outbreaks are coming from and possibly suggesting an upstream intervention to limit further infections. The applications of these approaches are wide-ranging, including prediction of antimicrobial resistance and vaccine-resistant variants. However, there are still many clinical laboratories around the globe that lack the resources to run these technologically sophisticated diagnostic tests. This problem may be reduced by the development of point-of-care diagnostics that do not require an advanced laboratory.

These approaches have also allowed us to shift from focusing on the person who is infected to the transmission of pathogens in the environment. For example, testing wastewater for the SARS CoV-2 virus has provided valuable insights into the location of infections during the COVID-19 pandemic. This focus on transmission also allows implementation of the One Health lesson that human diseases are frequently acquired from animals or the environment. The focus on monitoring potential pathogens in the environment has catalyzed the development of a variety of new approaches for pathogen detection, from the use of smartphones and nanomechanical sensors to smart dust. Several of these innovative new approaches are described in the article "One Health: The Benefits (and Risks) of a Comprehensive Diagnostic Approach." But there is clearly more to come: This is rapidly evolving field, with many entrepreneurial opportunities that will likely compete in the marketplace over the next decade.

Some major challenges we have faced with testing for SARS CoV-2 have included the limited availability of supplies needed for testing, inadequate numbers of trained microbiologists in clinical laboratories, and a distrust in some communities that the results are important, reproducible and accurate.

For any of these diagnostic approaches to have sufficient impact to thwart the COVID-19 pandemic or the next pandemic, the public has to trust that the approach is effective and reliable, and that their privacy is protected.
For example, the article on "One Health" emphasizes potential privacy issues that may arise from environment-based diagnostic approaches that may pinpoint a particular community. We need to solve these issues before they become a problem that negatively impacts people's lives, so scientists cannot shy away from ethical issues when designing diagnostic solutions.

Sadly, another concern is fraudulent claims about the effectiveness, sensitivity and reliability of diagnostic tests. The article "Consumer Beware: The Cost of the Rare Fraud in the Biomedical and Diagnostics Industry" describes examples of ineffective products that were promoted by unethical charlatans enticed by financial rewards. These cases are rare in the life sciences industry because of the scrutiny of the FDA, as well as the role of peer reviewers and the scientific community in carefully analyzing the published data that is the cornerstone of most new products. These rare infractions emphasize why it is so important for scientists to have a robust knowledge of scientific ethics, and why this is such a critical component in the training of new researchers.

Although microbiologists have made tremendous strides in responding to infectious diseases, a core concept of microbiology is that there is a tremendous number of microbes, and these numbers allow them to evolve new properties very rapidly. Insights into these mutated microbes often depend on knowledge that we don't yet have and can't predict a priori. As argued in Vannevar Bush's 1945 report "Science: The Endless Frontier," critical new insights frequently come from fundamental research. So, if we are going to be prepared for the next new pathogen or the next pandemic, we need to pay close attention to basic research and research on pathogenesis per se. The article "What's Hot in the Microbial Sciences" includes some published articles that address directed research on pathogens, but also some articles that we thought were interesting, clever and – who knows – may someday lead to an application that makes the world a healthier place.