There are seven people. Five of them, women. They work on the GSK pharmaceutical campus in Tres Cantos, half an hour from Madrid. And until now, they did it in biosafety level 3 (BSL-3) laboratories, the penultimate step of biological danger. Now, five of the 27 BSL-3 rooms that the company had in this complex have been converted to house two rooms of the first Spanish laboratory that will work at the maximum level of biosafety: the BSL-4. The jump is not only technical. It is, to a certain extent, existential.
BSL-4 laboratories represent the highest level of biological containment. They work with the most dangerous pathogens on the planet, those that cause serious or fatal diseases for which there are no treatments or vaccines, such as the Ebola virus or the Marburg virus. “In BSL-3 you work with serious pathogens, but there is treatment. For those at level BSL-4, there is no prevention or treatment,” confirms David Barros, director of R&D in Global Health at GSK in Spain, during a visit that the company has organized this week for different media, including EL PAÍS.
Currently, there are eight institutions that have BSL-4 laboratories in the European Union. In the world there are 51 in 27 countries, according to the report Global BioLabs 2023from King’s College London. The Spanish Government is building its own BSL-4 at the Carlos III Institute facilities in Majadahonda, which is expected to be operational next year. The Government has signed a collaboration agreement with GSK, and the president himself, Pedro Sánchez, visited the laboratory on March 3.
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This is the new GSK laboratory in Spain
The idea of setting up a BSL-4 arose at GSK during the Covid pandemic. The Tres Cantos center, specialized in infectious diseases, then focused on this virus. “The pandemic awakened the appetite of some of the people here to have this laboratory. And we asked ourselves if it would be very difficult to do so. Then we realized that it was almost an obligation,” confirms Barros.
The center, with more than 30 years of history and a hundred researchers, is dedicated almost exclusively to the discovery of drugs against infectious diseases that affect vulnerable populations, mainly malaria, tuberculosis and antibiotic resistance. Their director prefers to call them “neglected diseases,” rather than “tropical” or “ignored.” This center has produced, among others, tafenoquine, a single-dose treatment against a particularly treacherous form of malaria that can remain silent for months in the liver, and the discovery of a bacteria that colonizes the intestine of the mosquito and makes it incapable of transmitting the malaria parasite.
With 27 active BSL-3 rooms, the conversion of some of them into BSL-4 represented a reasonable investment for a large pharmaceutical company like GSK: 5.2 million euros and, almost more importantly, researchers already trained, for many years “and no accidents in 30 years”, highlights the company, in BSL-3.
When the company began considering setting up a BSL-4 lab, it asked how many of its researchers would be willing to risk their lives, literally. And the precise definition of a BSL-4 pathogen is revealing: these are biological agents capable of causing serious or fatal diseases for which there is, as of today, neither effective treatment nor vaccine. The first two targets of the Tres Cantos team are multidrug-resistant tuberculosis — for which existing treatments have stopped working in half a million people each year around the world — and Crimean-Congo hemorrhagic fever, a viral disease transmitted by ticks, which is already endemic in the Balkans, for which there is no vaccine or approved antiviral and which has a “high pandemic potential,” says Barros.
Seven of the researchers responded positively and have already been trained, in Spain and England, to use BSL-4.
Inside the laboratory
The pressure they are going to be under is enormous. And the safety of the use of the laboratory, too. Entering BSL-4 is not like entering anywhere else. Researchers must remove all their clothing, including underwear, in changing rooms. Afterwards, they shower and dress in their laboratory clothes. If they wear glasses, they have a duplicate.
They enter two by two and work in “mirror”, that is, they look at and evaluate each other, they ask a series of questions and it is the partner who authorizes the passage of their other partner. They dress in a full-body positive pressure suit—colloquially called a “spacesuit”—that includes an independent supply of oxygen and is hermetically sealed. Putting it on takes time; take it off, too. Between the entry process, work and exit decontamination, logistics consumes a considerable part of the day; It can take up to an hour and a half. You can’t take a quick pause. You can’t go out to drink water. You can’t go out to the bathroom. The concentration must be total throughout the duration of the experiment. At most, four hours can pass inside.
A BSL-4 laboratory is, basically, an extreme version of a BSL-3: everything is duplicated, shielded and designed so that absolutely nothing can escape. While in a BSL-3 the air that leaves is filtered, in a BSL-4 the air that enters is also filtered, not once, but up to four times with the most demanding filters on the market. The waste cannot leave without being decontaminated twice within the facilities themselves. Negative pressure – which means that air always flows in, never out – is guaranteed even in the event of a power outage, thanks to top-class uninterruptible power supply systems. And the most hazardous material is transferred through special airtight containers without anyone having to open a door. In BSL-3 there are already strict protocols; in BSL-4, each of them has a built-in plan B.
“While you’re inside, the valves are sealed, the system is totally closed from the outside environment,” says Javier Gamo, director of Global Health R&D Medicines at GSK. The center’s two BSL-4 rooms are independent of each other: each can house a different pathogen and operate completely autonomously.
Safety is the laboratory’s main priority, as stressed at GSK. The competent authorities may inspect it at any time and without prior notice. It is not a minor detail: according to the report Global BioLabs 2023three-quarters of the world’s BSL-4 laboratories are located in urban areas, amplifying the potential risk in the event of an accidental release of a pathogen. Tres Cantos, less than 30 kilometers from Madrid, is no exception.
The laboratory already has certification from the Community of Madrid. Internal validation will be completed in April. Afterwards, the team will begin to work progressively at levels 2 and 3 before reaching full level 4, expected at the end of 2026 or beginning of 2027. All the company’s researchers undergo regular health checks, but they will be especially monitored. By then, the seven researchers will have practiced the entry and exit rituals for months, and will have rehearsed each protocol until it becomes automatic. And one day, for the first time, they will come in with a real pathogen.
