¶¶ÒõÈÈÃÅ

George F. Gao walks briskly through the George R. Moscone Convention Center in San Francisco, where he's just taken part in an animated panel discussion about the contributions of microbiologists in the international response to outbreaks like Ebola. Five years ago, Gao was in a very different setting. The West African Ebola outbreak had been ongoing for several months and showed no sign of containment. As then-Deputy Director-General of China Centers for Disease Control and Prevention (China CDC), Gao spent 2 months in West Africa with his China CDC team as they assessed the on-the-ground infrastructure and opened mobile testing labs for diagnosing infected patients.

The Ebola outbreak began in Guinea and fear of the spreading infection led Guinea to with Sierra Leone and Liberia to contain the disease. The number of reported cases continued to grow through the end of 2014, peaking in September in Liberia and in November in Sierra Leone. The motivation to contain an outbreak is understandable, but man-made borders aren't respected by infectious disease. "Any pathogen, any virus—they don't need a passport to travel," Gao says. "They don't need a visa."

Unlike microorganisms, Gao does need a passport and his is well-worn. "Two days ago, I was in Sydney," he says. "Today, I'm sitting in San Francisco. In 2 days, I'll be in Beijing." Gao's intense energy belies any exhaustion he may be feeling due to his rigorous schedule. His roles as Director-General of the China CDC, as professor and director of the Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology and as Vice President of the National Science Foundation of China make Gao an in-demand scientist around the world. His expertise has helped in the fight against SARS, Ebola and influenza, among other infectious diseases.

Gao is sitting on the ¶¶ÒõÈÈÃÅ Microbe 2019 session panel because of his experience on the ground during outbreaks, but his basic scientific training has clearly influenced his ideas about public health applications. Over the course of the next hour, 2 experiences echo repeatedly throughout the conversation: 1: field work is vital for scientists to understand the real-world applications of their scientific discoveries. And 2: basic science is fundamental for laying a foundation upon which new scientific applications can be built.

Coordinating China's Role in the Ebola Response

Gao and China CDC played a critical role during the 2014-16 Ebola outbreak in West Africa, building the infrastructure necessary for patient testing, treatment and recovery. Gao pushed for these actions after spending time in Sierra Leone, arguably the heart of this outbreak. His visit informed the China CDC response as the case numbers continued to build throughout Guinea, Liberia and other West African countries.

The epidemic began in late 2013 in a small village in Guinea, likely due to a spillover event from bats. It was officially declared an epidemic by the World Health Organization (WHO) in March 2014, and by July of that year the outbreak had spread to the capitals of neighboring Liberia and Sierra Leone. This was the first urban Ebola outbreak where the larger, denser population meant person-to-person transmission occurred more easily and became harder to trace. It was Gao's experience in Freetown, Sierra Leone that spurred him to pen a column in Science about .

Gao visited Sierra Leone in 2014. While there, he recognized the role that infrastructure plays in both spreading the disease and putting a stop to its transmission. At that time, Sierra Leone had fewer than 100 registered doctors to identify sick patients, as well as scarce facilities to properly quarantine, treat and rehabilitate the infected. Gao recognized that better infrastructure would be necessary to quell the epidemic, and also more boots on the ground.

China provided not only badly needed infrastructure and supplies during the epidemic, but also hundreds of trained medical workers who . China was also the first to set up a medical facility in Liberia, providing 280 medical staff. The workforce and infrastructure China provided, such as mobile Biological Safety Level 3 (BSL3) laboratories to safely test and diagnose patients, was critical to successfully quenching the outbreak, which was , 2.5 years after the index case.

On-the-Ground Development of Basic Technologies

Gao's on-the-ground experience helped him gauge the real-time environment in Africa. Back in San Francisco, he explains how all scientists should spend time away from the bench to better understand the everyday challenges in disease-endemic regions. "Everyone should go [to these regions], including those who are doing basic research, like me," he says. "What is the most important scientific question to be answered? You can only learn this by going into the field." Traveling to the field is especially important for those who work in medically related or public health fields. "That tells you where the problem is, what the major issues are and what the hurdles are for implementation of public-health measures," Gao says.

Gao's true passion is basic research. He trained as a veterinarian in China immediately after China's cultural revolution, then earned his doctorate from Oxford and did a postdoctoral fellowship at Oxford and Harvard to specialize in structural biology. His lab has characterized structures of viral, bacterial and host proteins important for infection and his affection for these fundamental discoveries may be why he sees basic research as foundational for applied and public health microbiology.

Take nucleotide sequencing, for example. "Some would say [sequencing] looks like basic research, that A, G, C, T nucleotide sequence has nothing to do with public health," Gao says. "But that's wrong." Sequencing plays many roles during an outbreak, including providing an answer to the following question: Would vaccine research-development efforts be in vain?

In Freetown and other urban centers, the Ebola virus was passing from person to person in long chains of transmission that had not previously occurred. As a virus enters a new host species (in this case, human beings), it needs to adapt. "We ran quite a few virus sequences, which told us that the virus mutates very quickly," Gao says. Such rapid viral adaptation may influence the immune response to the virus or, worse for vaccine development, key viral protein epitopes. Gao's team generated 175 genomes by whole-genome sequencing (WGS), allowing . The scientific team used this technology to confirm that the virus's mutation rate would likely not affect the efficacy of vaccines then under development (and since produced) based on historically isolated viral strains.

The Ebola outbreak facilitated the on-the-ground application of still-developing technologies, including new sequencing technologies. At the onset of the West African Ebola epidemic, the pocket-sized Nanopore DNA sequencer was still new to the sequencing world and not yet commercially available. and proof-of-concept trials had been largely run in controlled lab settings. However, its portability and quick data turnaround allowed scientists to quickly assess and halt the chains of disease transmission, proving that basic research to develop methods can have —including new methods addressing what might be considered "solved" problems.

Basic Research Lays the Foundation for Public Health

In addition to the development of new methods and technologies, Gao encourages a very basic application of these sequencing technologies: descriptive science. One of Gao's recent collaborative projects is the , which aims to detect the majority of the planet's unknown viral pandemic threats. The ambitious goal is to prepare for future pandemics so that public health officials can take a proactive, rather than reactive, stand against disease outbreaks.

The Global Virome Project was announced with great fanfare among the disease ecology and biopreparedness communities, but not without . Gao supports the Global Virome Project, citing his experiences with SARS, MERS and Ebola as viruses that emerged to cause major outbreaks, and was one of the authors of the . However, he remains practical about the finances involved. "The potential to have an emerging virus is always there, so of course I think it's worthwhile," he says.

Merely listing the global population of viruses won't suffice for pandemic preparedness, since determining the risk from each new virus requires careful study. How can scientists understand which viral characteristics they should assess to prevent the next outbreak? Gao's answer: basic science, such as what he does in his own lab. "My work is on interspecies transmission," Gao says. "Through adaptation, through evolution, some viruses may adapt to human beings." These adaptations, Gao says, can be detected through the basic research that might help to define characteristics of zoonotic viruses or the receptors likely to interact with human ligands. Answering the why and how surrounding these characteristics, what one might call "mechanistic studies," can help to determine which viruses should be monitored for potential human transmission.

Much of Gao's research efforts come from his role with the Chinese Academy of Sciences, where he runs a lab of around 20 scientists. Gao has amassed a collection of sera from many different sources: various species, geographies and time points. He shares these through collaborations with disease researchers who want to study their favorite microbe. This generosity of collaboration is one reason why Gao has published on Ebola virus, Rift Valley Fever virus, Chikungunya virus, enterovirus B, human immunodeficiency virus (HIV), hepatitis C virus, tick-borne encephalitis virus and yellow fever virus—all in 2019 (plus work on ribosome biogenesis, bat immunity and PD-1 tumor immune checkpoint therapy).

Gao sees collaboration for projects like the Global Virome Project as vital to the scientific process. However, collaboration alone is not the road to a successful scientific career. "To promote the science, to promote public health, to promote societal development, we need 4 Cs, which are collaboration, communication, coordination and competition," Gao says. "Don't forget: Competition is very important." Gao believes that scientists who leave the comfort of their labs benefit from speaking with their colleagues about the important questions in other lab settings and disciplines. Interdisciplinary communication is where new ideas are hatched, he explains, and often relationships between scientists contain parts from each "C" category.

Gao's newest role, as Vice President of the National Science Foundation of China, gives him the opportunity to promote interdisciplinary cross-pollination. He allocates funds for life sciences and medical sciences in this position, putting him in a position to decide whether to fund the basic research that he clearly values, or the development of applications derived from some of these basic discoveries, which are often more highly valued by the public. A balance between basic and translational research can be difficult to achieve.

"In the whole world, from the U.K. to the U.S. to China, we haven't solved that problem," he says. "Sometimes, it's very hard to identify which basic research has potential for translation. Of course, we are trying very hard to identify some potential basic research to put into translational application." Gao speaks admirably of the U.S. system, which not only offers government funds through NIH- and NSF-funded grants for academics and small businesses, but also has a well-connected venture-capitalist network to provide private funds. These networks can help identify and support scientists who want to develop their discoveries into innovative products for the commercial market.

There Is Only One Subject: The Earth

Getting out of the lab and into real-world situations where scientists must interact with society and other researchers can help answer questions that require multiple scientific disciplines. "We don't have subjects divided by nature," Gao says. "We ourselves, because of the limitation of our knowledge, limitation of our mind, limitation of our memory, we human beings divide it into different subjects. But when you go out to the field and look at nature, there's only one subject, and that's the Earth." Preparing oneself with interdisciplinary studies, such as Gao's background in veterinary medicine, structural biology and protein chemistry, can prepare a scientist to address truly interdisciplinary questions. Gao considers himself a student of all of nature, proclaiming, "I am a biologist."

Gao clearly has many roles to fill, including in central Africa. Despite his many duties, when Gao dedicates his attention, his focused and thoughtful answers reveal a quick, ever-processing mind. In thinking about the many roles in basic science and public health that Gao must juggle, one might wonder whether Gao carries a recently discovered mutation that allows some people to . Gao laughs at the suggestion: "I get 7 or 8 hours; I'm a normal person!" After a brief pause (Gao only ever pauses briefly), he continues, "What's important is how you spend your time awake."

Listen to an interview with George F. Gao on ¶¶ÒõÈÈÃÅ's Meet the Microbiologist podcast.