When people fall sick, doctors are unsure how to treat them, and it’s unclear how the disease is spreading, the world turns to its most daring and revered experts on disease. These scientists risk their health to answer questions about the most deadly viruses known to man: How does Marburg spread? Can Ebola be prevented? What is this unknown virus? Working at the highest level of containment, Biosafety Level 4 (BSL-4), virologists, microbiologists, and immunologists expand the frontier of viral knowledge.

In 1943, the first modern biosafety cabinet was invented by US Army soldier Hubert Kaempf, who was working in the biological warfare laboratories at Fort Detrick. His cabinet was an enclosed workspace with a glass panel separating the face from the experiment, and most importantly, an air conduction system that kept microbes from escaping into the lab. Forty years later, Australia opened one of the first modern BSL-4 labs in Geelong, costing about 200 million Australian dollars, or $600-700 million today. Now, more than 100 BSL-4 labs are in use worldwide, operating in over 30 countries. Inside these labs, scientists work with the most deadly viruses and make discoveries that carry worldwide impacts.

One country that has benefited directly from this high-security work is the Democratic Republic of the Congo. In 2018, there were two major outbreaks of Ebola across the country. Populations were plagued with fever, nausea, muscle pain, and, in severe cases, organ failure. Fortunately, researchers in Canada had been trying to cure Ebola since 2005. They had developed a virus named rVSV-ZEBOV , which was harmless and modified to wear a molecular “coat” resembling Ebola. While rVSV-ZEBOV appeared like Ebola to the immune system on the outside, its effects on the body were benign. The modified virus, administered as a vaccine, taught the immune system to recognise and eliminate Ebola. However, the vaccine wasn’t approved for human use until a BSL-4 worker in Germany was accidentally infected. In an unconventional use, the vaccine was administered and proved effective in curing the worker.

By 2018, the vaccine still wasn’t licensed, meaning it was not approved by any government for public use, but the outbreaks of Ebola in the Democratic Republic of the Congo required immediate action. The World Health Organization (WHO) allowed for emergency administration of the rVSV-ZEBOV vaccine, immediately vaccinating over 3,000 people during the first outbreak, and over 300,000 during the second. Now, the vaccine is licensed to a large pharmaceutical company, Merck, and is approved for use globally. Ebola research continues in BSL-4 labs today, alongside another infamous disease, Lassa fever.

Lassa fever is named after the city of Lassa, Nigeria, where two nurse missionaries had the first medically identified cases of the fever. Currently, there are 100,000 to 300,000 infections annually in West Africa. Some cases have spread to Europe and the United States through travel. About 1% of all cases are fatal, and mortality rises to 15% among hospitalized individuals . Survivors commonly suffer from hearing loss or other neurological complications. The primary vector is mice, transmitting the virus to people by contaminating household items or food with fluids. Previous vaccine variations required multiple shots, making it extremely difficult to administer due to the isolation of rural communities, high treatment costs, and lack of healthcare access. Additionally, previous developing vaccines took multiple weeks to take effect, and not a single one was licensed for public use. Enter: University of Texas Medical Branch’s Galveston National Laboratory.

In 2022, a team of virologists in Texas utilized the same methodology as the Ebola vaccine for a study on monkeys. They took the same harmless virus and put on the “coat” of Lassa. The results were astounding; a single injection vaccine provided 100% protection when given 7 days before exposure and protected the monkeys from multiple virus variants. While the Lassa outbreaks continue, this study could bring them to a close within the next decade. The benefits of BSL-4 discoveries are widespread and invaluable, but they do not always come without concern.

Controversy chronically revolves around pathogen research. In December of 2019, when COVID-19 emerged from a seafood wholesale market, the methods developed in BSL-4 labs helped to handle the virus and identify its genome at lightning speed. However, rumors emerged that the virus may have leaked from a high-security research facility. Most scientists agree that COVID-19 jumped from bats or a similar animal to humans, but the lab-leak rumors highlight an underlying tension: lack of trust between communities and the high-security research facilities they house. When Boston University received a federal grant to build its BSL-4 facility, NEIDL, in the South End of Boston, there was resistance from residents. Construction of the building was finished in 2008, but the lab delayed opening for ten years due to Bostonians’ concerns about the threat of disease to their community. While those outside the lab raise concerns for public health, those inside work to protect it.

Working inside a BSL-4 lab is a challenge of skill and fortitude. Training starts with theory seminars, followed by practical training to wear personal protective equipment and operate machines. Next, a period of mentored work and a final exam. The certification process can take months or years. When a scientist is ready to go into the lab, they suit up in a thick positive-pressure suit with an air hose attached. If the suit is punctured in the lab, air will blow out to keep microbes from coming in. Many BSL-4 labs require a fingerprint to enter, or even an iris scan, and leaving the lab requires an eight-minute chemical shower in a positive-pressure suit followed by a personal shower.

Once inside the lab, the real mental and physical demands begin. Emmie de Wit, as a National Institutes of Health researcher at a BSL-4 lab, said in a 2016 interview with NPR that the work requires being "very, very focused. You can't do anything else other than what you're doing at that moment. It's kind of a nice mode to be in while you're working. And it's very quiet." Scientists in the lab can communicate through radios in their suits or hand signals. This can be isolating for researchers; they often spend long hours in their suits because of the time and effort required to get in and out of them. It’s tedious work to conduct complex experiments and spend long hours in these suits, where if you have to scratch your nose or reset your glasses, it can take minutes to slip an arm up the suit into the headspace. Most work takes about three times as long as it would at a lower safety level lab. In addition to the working conditions, the threat of deadly viruses makes this job unlike any other. “It's all a matter of being trained extremely well to do this. Things can go wrong. Unexpected things happen, especially if you do animal work. It's in your own best interest for your own peace of mind to follow all the rules,” commented de Wit.

The future of public health is unpredictable, and the forecast is constantly in turmoil. The next epidemic could be just around the corner, lying dormant in an animal population, taking root in an unsuspecting victim. What is certain? Someone is trying to help. Epidemiologists are studying the spread of disease, medical staff are caring for the sick, and researchers are developing weapons against infection. The next threat could come from anywhere, but it will be met with burning opposition everywhere.