A year agothe Brazilian Center for Energy and Materials Research (CNPEM) announced that Brazil would be the first country in Latin America to have a maximum biosafety containment laboratory – called a P4 laboratory or BSL-4 for “biosafety level 4”. The project is taking shape: construction work began last month. The site, called Orion, is expected to be operational in 2028. While South American virologists are delighted, the public remains skeptical about the presence from this laboratory intended to host the most dangerous viruses in the region.
Maximum biosafety laboratories – known as P4 or BSL-4 – are designed to study the world’s most dangerous pathogens. These viruses and other microorganisms have very high mortality rates. For some of them, there is no effective treatment or vaccine. These facilities meet very strict standards, including complete and perfect sealing. The air flow is tightly controlled: no air from the place where the pathogenic compounds are handled must escape.
P4 labs typically have multiple decontamination airlocks and fire safety systems. Nothing leaves the lab (air, water, waste, equipment) without prior decontamination. Employees in these labs must adhere to very strict protocols when handling pathogens. They must wear a positive-pressure suit, take a chemical decontamination shower after handling, etc. In addition, they are under constant video surveillance.
Addressing the growing threat of zoonoses
There are about fifty of these high-security laboratories operating throughout the world, including three in France. One is in Lyon, the other two in the Paris region, in the Essonne department. According to a report published last year through the Global BioLabs initiative, their number is increasing rapidly. Most of the new construction is in Asia. Since the start of the COVID-19 pandemic, 12 new P4 laboratory projects have been built in nine countries.
The purpose of these facilities is to study dangerous live viruses up close and safely. Understanding how they work is crucial to developing effective vaccines and treatments.
Distribution of P4-type laboratories, operational, planned or under construction, in the world in 2023. Credits: Global BioLabs Initiative
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Experts fear that many new pathogens will emerge in the coming years. By destroying natural environments to expand cities or increase agricultural land, humans are promoting promiscuity with wild animals. However, these animals are potential reservoirs of viruses. A study published in Nature in 2020 warned of “increasing dangerous interfaces between humans, livestock and wildlife.”
At the same time, climate change is forcing some species to move. The consequences: new possibilities for viral sharing between species that were previously geographically isolated. We are sitting on a powder keg ” in terms of pathogens likely to emerge in Latin America, résumé Fernando Spilkia veterinary virologist at Feevale University in Novo Hamburgo, Brazil. For this specialist, the creation of a South American P4 laboratory is now essential.
The Ebola and Marburg viruses, the Lassa virus, the Crimean-Congo hemorrhagic fever virus, the Nipah virus, … These are all examples of pathogens studied in this type of structure. What do they have in common? In addition to combining the characteristics of lower-security infectious agents – namely the ability to cause human diseases and the absence of vaccines or treatments – they all have a mortality rate of over 60%.
The first P4 laboratory connected to a synchrotron
Currently, Sabiá virus is the only pathogen detected in Brazil that requires biosafety level 4. This arenavirus, which causes Brazilian hemorrhagic fever, is highly infectious and deadly. The first case of infection occurred in 1990 in São Paulo; the patient died. Fortunately, fewer than a dozen other cases—either naturally occurring or in clinical settings—have been reported since then. This virus is currently being stored in a laboratory in the United States.
Several other viruses are worrying South American specialists: Junín, Guanarito and Machupo among other arenaviruses. These viruses, which are found in countries bordering Brazil, also cause hemorrhagic fevers.
Until the pandemic, Brazil had few P3 laboratories, where pathogens such as SARS-CoV-2 can be analyzed. More dangerous infectious agents, such as the Sabiá virus, had to be sent abroad for study, says a press release of the FAPESP agencyHaving a level 4 laboratory could therefore mean greater autonomy for the country. It will free us from dependence on other countries to research the agents responsible for epidemics in our country. We will be able to develop our own vaccines and treatments. “, said Antonio José Roque da Silva, general director of CNPEM.
The Orion laboratory construction site is located next to a synchrotron facility at the Brazilian Center for Energy and Materials Research in Campinas. Credits: CNPEM
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The lab, called Orion, is located at the Brazilian Center for Energy and Materials Research (CNPEM) in Campinas, about 100 kilometers northwest of São Paulo. It is the first Biosafety 4 lab in the region, but that is not its only special feature. It will also be the first P4 lab to have a synchrotron light source.
Indeed, the CNPEM houses one of only three existing fourth-generation synchrotron light sources, called Sirius. Scientists use it to study the composition and structure of matter in various forms. Here, it will be used to reveal the structures of pathogens and how they infect host cells.
Cutting-edge technologies, highly qualified personnel
Specifically, Orion will be connected to three Sirius beamlines. Hence its name, in reference to the three-star constellation that points to the star Sirius. This will be the first time that a synchrotron radiation will operate under these conditions, which has raised additional technical challenges. Indeed, the beam hardware requires regular calibration and maintenance, so it must be located outside the BSL-4 part of the laboratory. To achieve this, the project designers planned to pass the beams through an optically transparent niche in a wall separating the synchrotron from the laboratory.
Like other such facilities, the site will also house lower-level biosafety laboratories, including BSL-2 and BSL-3 facilities. Orion will also house basic research laboratories, analytical techniques and advanced imaging technologies, such as electron microscopy and cryomicroscopy. It will also have laboratories for preclinical testing on non-human primates.
In parallel with the construction, CNPEM will lead a national training program for high and maximum biocontainment infrastructures. The objective is essentially to develop skills that are currently lacking in Brazil and other Latin American countries. A highly qualified permanent team will then be responsible for the maintenance and management of the site.
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All this comes at a cost. The Brazilian government has invested one billion reais (about 162 million euros) in the project. The maintenance of the site is also expected to be very expensive. According to Naturein 2022, Thomas Ksiazek, manager of high-level containment operations at Galveston National Laboratory (a P4 facility in Texas), said his lab requires nearly $12 million a year for maintenance and operations, including $2 million to provide 24-hour security.
Aside from the financial considerations, the nature of the project itself raises some concerns. Indeed, the COVID-19 pandemic has cast some doubt on the safety of the P4 labs. The Wuhan Institute of Virology, home to China’s first P4 lab, was studying coronaviruses taken from bats when the pandemic broke out. There is evidence that SARS-CoV-2 jumped from wild animals to humans. But some scientists still believe that an accidental lab leak is a possibility.
