September 24, 2017

Galveston National Laboratory is among the few labs in the world equipped to house and study the deadliest diseases. It plays an essential role in the nation’s defense against biological threats.

By John Flynn
Population Health Scholar
University of Texas System
Master's Student in Journalism
UT Austin Moody College of Communication

On the campus of The University of Texas Medical Branch, in Galveston, Texas, sits the Galveston National Laboratory. From the outside it looks like nothing special, just another mid-level, concrete building on a whole campus of them.

On the inside, however, it is like something out of a science fiction movie. Researchers pass through security checkpoints and airlocks in order to enter, with each threshold building on the safety precautions of the previous. In the Biological Safety Level Four (BSL4) laboratories they positive pressure suits with hoses connecting them to airflow. The air itself is perpetually disinfected through High-Efficiency Particulate Air (HEPA) filters, while all liquid and solid waste is “cooked” by a sophisticated heat, pressure, and chemical system before it leaves the laboratory.

The bones of the building, too, hide secrets. Support pilings go 120 feet into the ground. All labs are locked at all times and are located at least a few stories up, above the reach of anything less than a tsunami of historic proportions. In the event of any potential threat, the lab is able to rapidly shut down and decontaminate. And the structure itself is so sturdy it should be able to withstand a category five hurricane. (It survived Hurricane Harvey with no damage and no interruption to operations.)

To even get into the innermost sanctums of the building, researchers have to pass stringent FBI security checks, undergo thorough health assessments, do months of training and education, and apprentice to experienced researchers.

There is a simple reason for all this complexity. Or rather, a host of reasons, many of them with names to conjure nightmares: anthrax, Ebola, avian flu, bubonic plague, typhus, Zika, West Nile virus, drug-resistant tuberculosis, and more.

In order to protect ourselves against such deadly pathogens—to develop improved means for the prevention, diagnosis, and treatment of the diseases they cause—researchers need a safe place to study them. It has to be safe for the researchers, safe for the public outside, protected from possible theft or attack, and in compliance with national and international guidelines on how to deal with dangerous biological agents.

To address these concerns, the US Centers for Disease Control and prevention (CDC) has designated four levels of biocontainment, each one building on the safety precautions of the previous. The deadliest pathogens are housed in BSL4 laboratories.

Galveston National Laboratory and the smaller Robert E. Shope Laboratory, which is also on the UTMB campus, are the only BSL4 labs in the United States owned by a university, and among the few labs in the world equipped to house and study the absolute deadliest diseases. They play an essential role in the nation’s defense against biological threats, including natural epidemics and bioterrorism.

Building a New Biodefense

In 2001, shortly after the 9/11 attacks, letters laced with spores of anthrax, that began appearing in US mail. The attacks left five people dead and infected 17 others. In response to the attacks, and to the broader threat of bioterrorism, the federal government boosted funding to the National Institutes of Health (NIH) to promote biodefense.

At the time, UTMB was already operating the smaller BSL4 Shope Laboratory. When the federal government requested proposals for the construction of two new BSL4 labs, UTMB’s experience allowed it both to win the bid and to build the new facility in less than three years. It opened for research in 2008 with BSL2-BSL4 capacity, including 12,222 square feet dedicated to BSL4 lab space.

In the past nine years, GNL has become one of the primary sites globally both for basic research into the epidemiology and ecology of the most dangerous pathogens, and for translational work focused on clinical trials and product testing and evaluation. During the 2014 Ebola outbreak, almost every vaccine or experimental treatment was tested at GNL at some point. It has a played a similarly vital role in the more recent global response to the threat of the Zika virus.

Although the original funding for the construction of the lab was directly tied to terrorism, the researchers themselves care as much about naturally emerging infectious diseases as they do about those that could be spread maliciously. The goal in either case, says lab director Dr. James LeDuc, is to develop improved means for the prevention, diagnosis, and treatment of life-threatening diseases.

“A vaccine against anthrax can work in response to an emerging infectious disease as well as to a manmade incident,” says LeDuc, who worked for the US Army, the CDC, and the World Health Organization before coming to Galveston. “We focus on the pathogens rather than the source.”

The Rise of Zika

When the first global Zika epidemic emerged in 2007, most public health officials and infectious disease researchers were taken off guard. Up to then, Zika had been an obscure virus that was hard to diagnose and didn’t infect many people globally.

Dr. Scott Weaver, Scientific Director of GNL and Director of UTMB’s Institute for Human Infections and Immunity, was one of the few people in the world who wasn’t surprised.

The Zika virus had never been the primary focus of his research, but he was an expert on mosquitoes and on vector-borne diseases, like dengue and chikungunya, that were similar to Zika. Over the course of a long career he had done some work studying Zika in Africa and Cambodia, and in 2007 happened to be one of the researchers on the single National Institutes of Health-funded project that looked at Zika.

He and some infectious disease colleagues had even predicted, in a number of papers, that it might someday emerge as a global threat to humans.

When someday became right now, Weaver and his colleagues were able to respond to the outbreak quickly. They shifted more of their resources to studying Zika, and UTMB quickly emerged as one of the key global centers for research on the virus.

Weaver and his colleagues now do a range of work on Zika, everything from analyzing the DNA of Zika-infected mosquitoes to better understanding how the virus replicates, to developing potential vaccines, to consulting with local, national, and international public health agencies on how best to contain the spread of the disease.

Zika is a vector-borne disease transmitted to humans primarily through mosquitoes. A person bitten by a Zika-infected mosquito can incubate the virus and then become viremic (when the virus enters the bloodstream). If they travel to another location and are bitten by mosquitoes there, those new mosquitoes then can become infected and transmit the disease to more people.

“If the mosquito infects more than one person, then the outbreak is amplified,” says Weaver.

What this means, says Weaver, is that a comprehensive strategy to limit or end Zika outbreaks will focus not just on developing vaccines against infection, but on treatment for those who are infected, and on mosquito control strategies designed to diminish the sheer number of infected mosquitoes in vulnerable regions.

The work, says Weaver, is both low-tech and high-tech, and slow and fast.

“There are several promising Zika vaccines already in clinical trials since last year’s outbreak,” says Weaver. “That speed is unprecedented. At the same time, despite many decades of attempts to control Aedes aegypti mosquitoes, we really aren’t doing much better today than decades ago.”

In many cities, he says, there is no dedicated service to control mosquitoes, and funding for mosquito control tends to be highly contingent on the perception or reality of a pressing threat. When something like Zika comes along, it can take time both for new money to be allocated and for the tools and expertise in mosquito control to make it out to the most vulnerable regions.

In 2016, in response to the threat, Congress allocated more than $1 billion to fight Zika, part of which went to funding four big grants for Centers of Excellence in Vector-Borne Diseases. With Weaver as principal investigator, UTMB partnered with seven other universities, seven local public health agencies, and the Texas Department of State Health Services to apply for one of these grants. They won the bid, and the Western Gulf Center of Excellence for Vector-Borne Diseases is now on the front lines of fighting Zika and other vector-borne diseases.

“The CDC made some smart decisions to incentivize us to work together,” Weaver says. “The idea is to connect the CDC level to the researchers like us all the way down to public health officials at the municipal level.

The program involves a mixture of applied research to develop better ways to monitor and control mosquito populations. There is also an emphasis on improving surveillance of both mosquitoes and infections, since good epidemiological research and optimal public health strategies are dependent on knowing precisely where and when the disease is being transmitted. There will also be education programs for doing mosquito surveillance and control, especially in the Rio Grande Valley area.

Researchers hope the combination of local vector control and research on vector-borne diseases can help hinder their spread.

Predicting, Responding, and Waiting

Unlike more traditional research laboratories, even those with a focus on treatments and therapeutics, GNL has to be acutely responsive to what is happening in the outside world. When crises emerge, like Ebola or Zika, substantial resources are shifted to focus on the threats.

Even better, say LeDuc and Weaver, is when researchers can anticipate epidemics and begin the process of developing vaccines, treatments, and public health strategies years before an outbreak.

With Zika, for instance, their understanding of the virus was more advanced than it would have been if Weaver and others had not foreseen its potential as a threat. This foresight did not translate into immediate vaccines, but it is likely that it accelerated the process. Vaccines may come sooner than they otherwise would have.

“By doing this research we can discover points of vulnerability in the pathogens where we can develop vaccines and treatments,” LeDuc says.

Researchers at GNL began doing work on the chikungunya virus in 2007, even though the mosquito-transmitted disease wouldn’t reach the United States until 2014, because they were paying attention to its spread in other parts of the world.

“We knew a new outbreak was emerging in East Africa and had very strong suspicions that it would arrive in the Americas,” says Weaver. “We made our case to the NIH and other funding agencies that we needed to be proactive, and they placed chikungunya on a priority list for emerging viruses. We started working on chikungunya vaccines in 2007.”

Even with this much advance notice, however, a vaccine still was not ready by the time chikungunya reached Florida in 2014 or the Rio Grande Valley in 2015.

“It’s a very slow process to move through all of the clinical testing,” Weaver says. “We did what we could with vector control, but it had little to no effect on the impact of the spread of the outbreak. It can be frustrating.”

The pace of development, say Weaver and LeDuc, is a result of a few things. One is just the standard process of clinical testing of drugs and vaccines, which is slow in most cases, because the government doesn’t want to approve new drugs before making absolutely sure they are safe. Working with dangerous pathogens like Zika and chikungunya can slow the process even more, since the nature of the work requires extreme precautions. And vaccine and drug development is expensive. Clinical trials are typically funded by big pharmaceutical companies, and the incentive is minimal to fund vaccines or treatments for diseases that haven’t even emerged as a major threat yet, or that only emerge periodically.

Weaver gives the example of Ebola. There were Ebola vaccines tested in animals many years before the 2014 outbreak, but despite the international attention on that outbreak, the vaccines that could have been put into clinical trials—vaccines that were shown to be efficacious through normal scientific design—didn’t make it quite in time for traditional evaluation designs.

“There was one vaccine that was tested near the end of the outbreak, and some evidence that it protected was obtained, but we still don’t have a licensed Ebola vaccine,” Weaver says.

Although exotic sounding diseases like Zika and Ebola tend to get more media attention, LeDuc says the biggest perennial threat to public health is the potential for pandemic influenza.

“Things like avian influenza, if these adapt to human to human transmission, it is a very serious problem because the human community lacks an immunity to it,” he says. “The worst case scenario is when a new disease emerges with a susceptible population.”

It is this kind of scenario that keeps researchers like LeDuc and Weaver working around the clock—sometimes literally 24/7—to understand and develop vaccines for the deadliest pathogens known to man.

“We’re always on the lookout for whatever the next emerging disease is on the horizon,” says LeDuc.