A study examining the origins of AIDS recently made headlines for debunking the infamous myth that Gaetan Dugas, the French-Canadian flight attendant dubbed “Patient Zero,” brought the AIDS pandemic to North America. The less sensational but perhaps more important story from that study is about the technique the researchers used to create their unprecedented understanding of the disease’s beginnings and initial spread, a technique that could revolutionize the fight against infectious disease outbreaks.
The international team of researchers sequenced the genomes of HIV viruses that had been recovered from more than 2,000 blood samples taken in the late 1970s — before AIDS had been identified in the United States. By comparing those sequences to other strains of HIV in the Los Alamos National Laboratory HIV database, the scientists were able to build a family tree of the disease, also known as a phylogeny. From there they were able to work out which strains were descended from which, how each one was transmitted, as well as how they may have mutated as they spread from place to place and person to person.
That AIDS study is just the latest prominent example to show the profound benefits of genomics and bioinformatics in improving our knowledge of public health crises. By using the evolutionary bioinformatic approach known as phylogenetics, scientists can better identify disease-causing microbes and determine their geographic origin, spread, and route of transmission.
As this powerful technique becomes faster and cheaper, mapping the full scope of a disease’s genealogy via phylogenetic testing shouldn’t be regarded as merely a method for understanding its past, but rather an essential tool in confronting future outbreaks.
The current tests used to identify causal agents in disease outbreaks provide useful information. Yet they are often too general and prone to error. These tests, typically a combination of less specific DNA analysis and tests measuring the immune system response to infection, do not definitively identify the exact species of a pathogen or a particular strain that may be resistant to treatment. In short, phylogenetic testing provides advantages to understanding outbreaks that current methods simply do not by providing more precise information about agents of disease as well as their evolutionary history, allowing for geographic tracking and calculation of how fast a disease might spread.
Tests that can establish the true pedigree of an outbreak can also eliminate errors that inevitably arise when we must heavily rely on personal accounts. Whether it’s hunting the source of a sexually transmitted disease or a foodborne illness, past experience proves that we simply cannot depend on the stories of individuals who may not wish to disclose, or simply might not remember, their past sexual partners or in which grocery store they bought a tainted apple.
Our current limitations on information gathering have very real, even fatal, consequences. In 2011, an E. coli outbreak in Germany was initially misidentified as originating from cucumbers in Spain. This outbreak cost 53 people their lives and hundreds of millions of Euros in damage. The actual culprit, finally identified using phylogenetic approaches, turned out to be sprouts from an organic farm in Germany’s Lower Saxony region. Using phylogenetic analysis on the front line may have helped officials more rapidly identify the correct source of the outbreak and the appropriate response.
Analyzing a microbe’s evolution can also help public health officials sift through the genomic variation in the infectious agent and quickly pinpoint the precise mutations causing a disease outbreak. In another recent example, researchers were able to confirm that a specific mutation during the 2014 Ebola outbreak caused a dramatic increase in infectivity in humans, which helped explain why that particular outbreak was so devastating.
Accurate identification of pathogens, knowledge of where and how they spread, and what treatments they might be resistant to are all fundamental questions that must be answered in each disease outbreak. While phylogenetic testing can do this, it is still an infrequently used tool in our first line of defense. That needs to change.
Public health investigations should routinely incorporate testing that includes a disease’s full ancestral map, and we should ensure that our officials get training to properly interpret the data. If all this information was widely available to the CDC or to the myriad departments of public health across the country and around the world to make informed, targeted interventions, it would lead to faster and more accurate responses to novel outbreaks of disease.
Phylogenetic testing can kill counterproductive myths like Patient Zero of the AIDS pandemic. But, more importantly, it has the potential to save countless lives.
Keith A. Crandall, PhD, is the director of the Computational Biology Institute at George Washington University.