Chapter 1: The Rise of a New Epidemiological Approach

In recent weeks, Trevor Bedford, a biologist based in Seattle, has gained significant recognition as one of the leading epidemiologists globally. His Twitter activity, which garners attention from top scientists and health policy makers, has attracted over 170,000 followers, with new ones joining daily.

Unlike traditional epidemiologists, Bedford, who operates from the Fred Hutchinson Cancer Research Center, does not engage in fieldwork to trace Covid-19 contacts. Instead, he collaborates with a small team of scientists across the globe—from Seattle to Basel, Switzerland, and Wanaka, New Zealand—to analyze hundreds of viral genomes from patient samples. This innovative approach helps them trace the origins of outbreaks, understand their spread, and detect early signs of infection clusters.

The team focuses on monitoring viral mutations that occur over time as the virus spreads. The coronavirus, with an RNA structure of about 30,000 genetic bases, mutates approximately twice a month. While these mutations may not significantly alter the virus's potency, they serve as vital clues for genetic detectives, enabling them to construct extensive “family” trees, or phylogenies, illustrating how the virus has traversed the globe.

Bedford's timely insights, shared swiftly via Twitter, have proven remarkably accurate, elevating his status among scientists and public health officials.

“In the early days, Trevor Bedford provided one of the most meticulous analyses of this pandemic,” noted former FDA Commissioner Scott Gottlieb in a March tweet. “His projections regarding the emerging epidemic in the U.S. should be taken very seriously.”

Three weeks ago, as U.S. officials believed they had a handle on the situation, Bedford was among the first to assert that the virus had been circulating unnoticed in the Seattle area for several weeks. His analysis indicated that the first known patient in Washington, a 35-year-old man who had recently traveled to Wuhan, China, likely infected others, allowing the virus to spread covertly.

“There are significant implications here,” Bedford remarked in a Twitter thread on February 29 that garnered thousands of retweets. “I believe we are confronting a substantial outbreak in Washington State that has gone undetected due to the narrow case definition that required direct travel to China.”

This genomic analysis diverges sharply from traditional epidemiology, which heavily relies on identifying infected individuals and tracing their contacts. “Instead of conventional methods that involve interviewing people about their contacts, we utilize pathogen genetics to understand their transmission patterns worldwide,” explained Emma Hodcroft, a molecular epidemiologist at the University of Basel who collaborates closely with Bedford.

Chapter 2: The Evolution of Genome Sequencing in Epidemiology

Genome sequencing has emerged as a powerful tool for tracking infectious diseases. During the 2014 Ebola outbreak in West Africa, genome analyses traced the origin of a transmission strain that had previously gone unnoticed, facilitating the understanding of the spread in Sierra Leone. However, that process took months. In contrast, genome sequencing is now routinely applied to identify sources of bacterial contamination in food.

Social media, particularly Twitter, has become indispensable for rapid communication. Bedford notes that he has long supplemented his scientific publications with Twitter threads, but the urgency of the pandemic has shifted his focus. “Once the first genome was released in January, I effectively transitioned to conducting science on Twitter,” he said.

Alongside the scientific discourse, Bedford often issues motivational messages. “We can bring this epidemic under control,” he asserted in a thread that received 5,000 retweets. “This is our generation's Apollo program. Let's get to work.”

In a comprehensive 19-part Twitter thread on March 18, he proposed strategies to navigate the crisis, such as implementing extensive in-home testing and drive-through sites to identify cases early, alongside utilizing cellphone location data to trace movements of individuals who test positive.

Bedford describes his newfound fame as surreal. “It’s been very strange,” he remarked. “While I receive attention for my work, so many others are facing severe disruptions in their lives.”

One of his key collaborators, Richard Neher, a computational biologist at the University of Basel, recalls how they conceived the idea of tracking viral evolution in real-time. Their initial focus was on influenza, aiming to assist vaccine developers in predicting which strains might dominate in the upcoming flu season. Over time, their website, Nextstrain.org, evolved to include data from various outbreaks, including Zika and Ebola.

When the coronavirus emerged, Bedford and Neher had already developed customized software for analyzing viral genomes rapidly. “We were able to hit the ground running because the foundational infrastructure was established,” Neher noted.

Nextstrain now operates continuously, staffed by researchers in Seattle, Basel, and New Zealand, ensuring global data analysis as soon as new viral genomes are uploaded to gisaid.org, a platform for sharing genomic data. It takes approximately 20 to 30 minutes to analyze a new viral genome, allowing for frequent updates.

Bedford envisions his work as complementary to existing virus-tracing methods, enhancing traditional epidemiology with new data streams. While the evidence he gathers does not definitively establish transmission chains, he suspects that “nearly everything we have observed in the Seattle area is part of the same transmission network.”

He commenced analyzing coronavirus genomes from China as soon as they became available on January 10. Health officials were asserting that the virus had a limited capacity for human transmission, but Bedford's findings were alarming: the viral genomes were too similar, indicating that the infection had spread from a single source rather than from multiple animal transmissions.

“This genomic data provided one of the earliest and most compelling signs of sustained epidemic spread,” Bedford stated in a blog post on January 31. “I spent the week of January 20 alerting every public health official I know.”

While Bedford and Neher are constrained by the availability of genomic data—only about 1,000 patients have had their viral genomes sequenced compared to over 350,000 reported infections—they are piecing together a clearer picture. The majority of the coronavirus clusters currently surging in Europe and the U.S. likely stem from community transmission that had been quietly brewing for weeks.

“We initially thought,” Neher reflected, “that the problem was confined to China, but that was a misconception.”