Orion will be the world’s first maximum biosafety lab linked to a synchrotron light source

Scheduled to start operating in 2028 at the Brazilian Center for Research on Energy and Materials (CNPEM) in Campinas (São Paulo state), the lab will enable researchers for the first time in Latin America to study viruses classified as class 4, the highest category of biological risk.

By André Julião  |  Agência FAPESP – Next door to the building that houses Sirius, thanks to which Brazil belongs to the elite club of countries that have a fourth-generation synchrotron light source, work has begun on the construction of another innovative facility at the Brazilian Center for Research on Energy and Materials (CNPEM). This facility is Orion, which will be Latin America’s first maximum containment laboratory, certified to Biosafety Level 4 (BSL-4).

Until the pandemic, Brazil had few BSL-3 labs where pathogens like SARS-CoV-2, the virus that causes COVID-19, can be handled for research purposes. More dangerous infectious agents, such as the Sabiá virus, had to be sent abroad for study and analysis. 

Having Sirius was a key reason for the choice of CNPEM to host the first BSL-4 lab in the Americas apart from the United States and Canada.

“It will also be the first BSL-4 lab in the world to be linked to a synchrotron light source. This uniqueness poses a number of challenges for us,” Antonio José Roque da Silva, Director General of CNPEM, told Agência FAPESP.

One of the challenges relates to the need to fit the three light sources created for Orion (called Sibipiruna, Timbó and Hibisco) into the structure of a BSL-4 lab. Viruses and other dangerous pathogens must be completely isolated with no possibility of leaks or exposure to the external environment, and synchrotrons have never before been used in such conditions of strict biosafety.

“The experiments are conducted in an extremely complex setting. It won’t be possible to put all the equipment for the light sources in a BSL-4 lab, so we’re designing a solution in which the samples, which are potential contaminants, will be totally isolated at the highest biosafety level. A team of international consultants who have ample experience with BSL-4 are helping us get there,” Roque da Silva said.

A matter of national sovereignty

Currently, Sabiá is the only known virus first detected in Brazil that can be handled solely in a BSL-4 facility. Sabiá is a New World arenavirus that causes Brazilian hemorrhagic fever. It was first isolated in Brazil in 1993 from a fatal case of hemorrhagic fever in metropolitan São Paulo. It will certainly not be unique in this way forever. Other equally dangerous pathogens are likely to emerge at some point in Brazil, in neighboring countries or farther afield.

To qualify for BSL-4, pathogens must have a mortality rate of more than 60% while also being compatible with the rules for BSL-3, especially the ability to cause disease, and lack of vaccines or treatments.

This is the case for Ebola, Marburg and Nipah, which are relatively well-known, but the criteria are also matched by Junín, Guanarito and Machupo, three other New World arenaviruses that cause hemorrhagic fever and are found in Latin American countries bordering on Brazil.

“The potential for partnerships with other Latin American countries to study diseases that can cause epidemics across the region is huge, but we’re also partnering with Germany, Sweden and the U.S. They’re all excited about our project,” Roque da Silva said.

COVID-19 underscored the importance of having labs equipped to store, replicate and analyze microorganisms that cause epidemics and pandemics, and to contribute to the development of vaccines and treatments. The virus that triggers the next pandemic may well be a class 4 pathogen, making the establishment of not one but several top-security facilities urgent.

Sabiá virus killed two people in 2019 in São Paulo. Brazilian researchers who wanted to study it were unable to do so. It is currently held at a lab in the U.S.

“A lab like the one under construction at Orion is an instrument of national sovereignty. It will free us from dependency on other countries for the purposes of researching agents that cause epidemics here. We’ll be able to develop our own vaccines and treatments,” Roque da Silva said.

Orion is being funded by the federal government via its Growth Acceleration Plan (PAC), which has allocated BRL 1 billion from the National Fund for Scientific and Technological Development (FNDCT), managed by the Ministry of Science, Technology and Innovation (MCTI). Completion is scheduled for 2026 and will be followed by two years of commissioning and startup. In addition to the BSL-4 lab, the building will also house BSL-1, BSL-2 and BSL-3 labs, as do other facilities of the kind around the world.

“Visits to several labs enabled us to see that the BSL-4 part is the smallest of all, corresponding to half of the BSL-2 portion in some cases. Most preparations, cells cultures, animal tests, and so on are conducted at the lower levels of biosafety,” he explained.

Orion will also have labs for preclinical trials in non-human primates. No such labs exist in Brazil at this time, yet they are key to developing vaccines and treatments without depending on foreign partners.

“Orion will raise Brazil to a higher level in various activities, involving not only viruses but also bacteria and fungi, as well as arthropods and other vectors. It will be open to the entire scientific community, as are CNPEM and its labs,” Roque da Silva said, referring to the institution’s four national laboratories: Synchrotron Light (LNLS), of which he is a former head; Biorenewables (LNBr); Biosciences (LNBio); and Nanotechnology (LNNano).

Governance

Whether Orion will have its own team of full-time researchers or will hold calls for proposals to execute specific projects has not yet been decided. According to Roque da Silva, the governance model is being discussed with the scientific community. In any event, a permanent staff of highly qualified personnel will be in charge of maintenance and management. Running the BSL-4 lab, a complex facility that will be unique in Latin America, will require professionals with up to 12 months’ training. 

Hence one of the first hires was precisely the head of training, Tatiana Ometto, an awardee of FAPESP scholarships for scientific initiation, doctorate and postdoctoral studies at the University of São Paulo’s Biomedical Sciences Institute (ICB-USP).

She was awarded a research internship abroad at the Viral Special Pathogens Branch (VSPB) of the Centers for Disease Control and Prevention (CDC) in Atlanta (USA), conducting postdoctoral research on some of the most dangerous viruses worldwide, such as Ebola, Marburg and Nipah, which can only be handled in a BSL-4 lab.

During the COVID-19 pandemic, she helped train health workers on the correct use of personal protective equipment (PPE) in hospitals and companies (read more at: agencia.fapesp.br/33511). 

Since she joined CNPEM, Ometto has taken a number of training courses and has been certified by the University of California, Irvine. The institution was recommended by partners at the National Institutes of Health (NIH), whose professionals train there to work in high-containment labs across the U.S.

“We have a space that simulates the environment in BSL-3 and BSL-4 labs, and where people must behave exactly as they would in a high containment facility. Even if you have BSL-3 experience, you require training to learn a number of special procedures,” Ometto said.

Dozens of people have graduated from CNPEM’s BSL-3 and BSL-4 Training Program since 2022, and there is a long waiting list for forthcoming sessions. If the number of professionals and partners who have applied for the program is anything to go by, there will be no shortage of qualified personnel to keep Orion in constant activity.