Included in the federal Growth Acceleration Program (PAC) and connected to Sirius, CNPEM plan funded by MCTI involves Latin America’s first maximum biosafety research facility (BSL-4)
Brazil will be the first nation in Latin America to have a maximum biosafety containment laboratory (biosafety level 4, BSL-4), and the first in the world connected to a synchrotron light source. With this facility it will join the group of countries able to deal with pathogens that can cause severe illness, including diseases that have not yet emerged.
The plan for the laboratory complex for advanced pathogen research is the responsibility of the Brazilian Center for Research in Energy and Materials (CNPEM), a social organization linked to the Ministry of Science, Technology and Innovation (MCTI), which developed and now operates one of the world’s three fourth-generation synchrotron light sources, Sirius.
Funded by MCTI, the project was just included in the federal government’s Growth Acceleration Program (PAC). This program comprises a set of public and private activities intended to accelerate growth in the country.
The new laboratory complex will span roughly 20,000 square meters to be constructed on the CNPEM campus in Campinas, São Paulo, and will include a new development in the history of synchrotrons and biosafety research labs worldwide: a connection with three of Sirius’s beamlines. Because of this connection, the project was named Orion, in reference to the constellation with three stars that point towards the star known as Sirius.
Besides BSL-3 and BSL-4 laboratory facilities and research stations that incorporate synchrotron light techniques, Orion will also combine basic research laboratories, analytical techniques, and advanced skills for biological imaging such as electron microscopy and cryomicroscopy.
This structure, which will be certified internationally, will permit research on diseases caused by class 3 and 4 pathogens, which cause severe illness and are highly transmissible. This project will also help train personnel in Brazil to be able to deal with this type of infectious agents. The requirements and scientific programs that comprise this project have been structured through discussions with various national research and health entities involving researchers from the domestic and international scientific communities, as well as public agencies such as the Ministry of Health.
The project, which has a budget of approximately 1 billion reais including human resources, is slated to be installed by 2026. Once the construction phase is complete, the complex will undergo technical and scientific commissioning and certification for international security standards in order to subsequently begin regular operations.
“This investment renews the MCTI and Brazilian federal government’s recognition of the strategic value of the projects CNPEM has been conducting over so many years. We are working to strengthen the national science, technology, and innovation system by providing competitive infrastructure to obtain answers for the most challenging problems that society currently faces, and for those that are yet to come,” says CNPEM Director General Antonio José Roque da Silva.
“The pandemic brought the importance of national control of a productive health foundation back to center stage, along with the government’s role in coordinating agents and investments to face the health crisis. Within this context, establishing a biosafety level 4 laboratory is strategic for the country. And the connection between the BSL-4 facility and the synchrotron light source will create major opportunities for research and development in the area of pathogens, positioning Brazil among the global leaders,” said Minister of Science, Technology and Innovation Luciana Santos.
Biosafety containment facilities
Today there are approximately 60 maximum biosafety containment laboratories worldwide, none of which are located in South or Central America or the Caribbean. This type of infrastructure combines a series of advanced, redundant measures for protection and biosafety that make it possible to handle class 4 viruses.
The first and only virus in this category identified in Brazil was the Sabiá virus (SABV), which causes Brazilian hemorrhagic fever, a disease diagnosed in humans in the 1990s and which has had new recent notifications. Although it was discovered in Brazil, the isolated samples of SABV are currently stored abroad; more in-depth study of the disease cannot be conducted in the country because of the lack of adequate infrastructure.
Besides SABV, a number of other viruses require BSL-4 infrastructure, such as other arenaviruses that circulate in Latin America: Junín, which causes Argentinean hemorrhagic fever; Guanarito, which causes Venezuelan hemorrhagic fever; and Machupo, which causes Bolivian hemorrhagic fever. Cases of disease caused by pathogens of this type are a reality in various places around the world, including Brazil. Even so, no Latin American country has the structure to monitor, isolate, and research these biological agents, much less develop diagnostic methods, vaccines, or treatments.
Dr. Maria Augusta Arruda, Director of the Brazilian Biosciences National Laboratory (LNBio) at CNPEM, recalls that not only are known pathogens constantly evolving, which could potentially cause more harmful variants, but population growth and deforestation also lead to imbalances in areas that could be natural reservoirs for illnesses that are still unknown.
“The efforts to find a way to control the Covid-19 pandemic are fresh in our mind; this same intensity was not seen when other high-risk infections were confined to poorer areas of the Global South, like Ebola. Above all, Orion is an instrument of sovereignty, allowing us to determine our priorities in this strategic area. Without a BSL-4 lab, we continue to depend on collaborations with other research centers abroad, depriving us not only of the speed to plan strategies to mitigate the harmful effects of this potential etiological agent, but also our society’s access to the resulting scientific and technological development,” she adds.
Sirius and research on pathogens
Sirius, the largest and most complex scientific infrastructure constructed in Brazil, utilizes electron accelerators to produce a special type of light called synchrotron light. This light is used to investigate the composition and structure of matter in a variety of forms, with applications in practically all knowledge areas. In a synchrotron light source, experiments are conducted in research stations called beamlines, where it is possible to observe microscopic aspects of materials like the atoms and molecules they contain, their chemical states and spatial organization, as well as to monitor changes over time in physical, chemical, and biological processes that take place in fractions of a second.
Sirius was planned to house up to 38 beamlines dedicated to different techniques and applications. Of these, three research stations will be connected to the Orion laboratory complex, something that has never been done anywhere in the world. According to Harry Westfahl Jr., Director of the Brazilian Synchrotron Light National Laboratory (LNLS) at CNPEM, which is responsible for operating Sirius, the beamlines integrated into Orion will be designed to allow research on biological materials at different scales. “These research stations will make it possible to extract quantitative structural data with respect to infected systems, from the subcellular scale up to the organism level. These beamlines will be the main research instruments for scientists to test hypotheses about the mechanisms of infection, using three-dimensional images to observe the chain of phenomena that lead to the development of illnesses generated by class 4 pathogens,” explains Westfahl.
By providing 3D images at different scales, the beamlines coupled to Orion will permit research ranging from studies of cells on the nanometric level to the dynamics of inflammation in tissues and organ damage up to monitoring the infection process in the entire body. Orion will make it possible to safely conduct research on pathogens, cells, tissue, and organisms, allowing the comprehension of biological phenomena related to how illnesses unfold and guiding the development of future diagnostic methods, vaccines, and treatments.
Like the other beamlines at Sirius today, the three lines that will be integrated in Project Orion will also be named after Brazilian flora and fauna: Hibisco, Timbó, and Sibipiruna.
Despite the challenges inherent to a project that has not been implemented anywhere in the world, the experience and skills acquired during the installation of Sirius, in terms of management as well as developing innovative technological solutions, provide both confidence and motivation to the interdisciplinary teams at CNPEM involved in Project Orion.
“The fundamental aspect of our experience with Sirius related to Orion is the similarity of the technical solutions, which prioritize safety and reliability. Nationalization of the solutions and knowledge in planning the subsystems also benefits Project Orion, which reduces installation costs, decreases uncertainties, fosters innovation, and permits more transparent, better planned, and safer operations. Sirius pioneered the construction of large-scale and internationally competitive scientific facilities in Brazil, and the maximum biological containment laboratory complex will be constructed along the same lines,” says James Citadini, Director of Technology at CNPEM.
Sirius also is included in the new government PAC plan and will receive funding over the next four years for the second phase of the project, which includes constructing ten new research stations and optimizing the facilities.
Training human resources
Alongside the construction and technological developments in Project Orion, CNPEM will lead a national training program for high and maximum biological containment infrastructure that focuses on developing human resources with skills that are not yet widespread in Brazil and other Latin American countries.
This training program includes partnerships with international institutions that are references for training Brazilian researchers in BSL-4 laboratories abroad. The program will also conduct training sessions in Brazil with hands-on activities in simulated laboratory environments and conditions at CNPEM (without infectious materials or risk of contagion) under the supervision of professionals trained to assess the individual skills of the researchers working under the conditions established in biosafety protocols.
With a sophisticated and vibrant environment for research and development that is the only one of its kind in Brazil and found in only a few scientific centers in the world, the Brazilian Center for Research in Energy and Materials (CNPEM) is a private, non-profit organization overseen by the Ministry of Science, Technology and Innovation (MCTI). The Center operates four national laboratories and is home to Sirius, the most complex project in Brazilian science and one of the world’s most advanced synchrotron light sources. CNPEM is home to highly specialized multi-thematic teams, globally competitive lab infrastructure that is open to the scientific community, strategic lines of research, innovative projects in partnerships with the productive sector, and training for researchers and students. The Center is an environment driven by research into solutions that impact the areas of health, energy and renewable materials, agri-environmental, and quantum technologies. Through the CNPEM 360 platform users can take immersive virtual visits to all the laboratories in Campinas (SP) as well as obtain information about the work conducted there and the resources available to the scientific and business communities. In 2022, with support from the Brazilian Ministry of Education (MEC), CNPEM expanded its activities with the opening of the Ilum School of Science. This interdisciplinary program in science, technology, and innovation implements innovative ideas to provide a high quality free and full-time undergraduate education immersed in the research environment at CNPEM.