Orion is a laboratory complex for advanced pathogen research that will be available to the Brazilian and international scientific communities investigating pathogenic agents (viruses, bacteria, fungi) and how they affect human health. The plans for Orion include Latin America’s first maximum biological containment facilities (BSL-4), and the first in the world connected to a particle accelerator, Sirius.
It will also contain BSL-2 and BSL-3 spaces, laboratories for basic research, analytic techniques, and advanced competencies for biological imaging, such as microscopy. The work that will take place at Orion will advance knowledge on pathogens and related diseases and support surveillance activities and public health policies.
All this infrastructure will benefit the development of diagnostic methods, vaccines, treatments, and epidemiological strategies, for example, in turn strengthening the Brazilian health system and fostering national sovereignty to face current and future health scenarios. Orion is overseen by the Brazilian Center for Research in Energy and Materials (CNPEM), a social organization supervised by the Ministry of Science and Technology (MCTI).
Orion will have the potential to benefit various areas such as health, science and technology, defense, and the environment, and will be available to the scientific community and public agencies to respond to health challenges that face Brazilian society.
Spanning approximately 30,000 m², it will include corporate areas, an animal research facility, laboratories for electron microscopy and cryomicroscopy, advanced bioimaging techniques, and a BSL-3/BSL-4 containment laboratory training center to train specialized professionals in Brazil for work in BSL-3 and BSL-4 settings.
Orion will have infrastructure and capabilities for pre-clinical trials, which are crucial for developing vaccines, diagnostic methods, and treatments. Analytic infrastructure, ample capacity for cell culture experimentation, capabilities for semi-automated bioassays at various biosafety containment levels, and various animal models for experimenting at biosafety levels 3 and 4 will allow advances in research that could evolve into clinical trials
Scientists will have access to a set of techniques for high-precision cell analysis, paving the way for fundamental discoveries in the field of infectious diseases. Cutting-edge equipment like metabolic assay platforms and spectral flow cytometry will allow in-depth studies of cellular metabolism and the identification and characterization of leukocyte populations. On a different scale, high-resolution mass spectrometry will make it possible to identify and quantify proteins and other biological molecules. Scientists will be able to combine the advanced technologies available at Orion to advance the frontiers of knowledge
Molecular biology is essential for identifying and characterizing infectious agents and toxins. Orion will have third- and fourth-generation sequencing technologies and platforms for quantitative and digital PCR for rapid and precise quantification of genes and genomes. There will also be tools for molecular cloning and genome modification like CRISPR-Cas9, which can be used to explore the biology of molecular targets and pathogenic microorganisms.
Advanced imaging technologies create possibilities for increasingly deeper understanding of the microscopic world. Techniques such as light sheet fluorescence microscopy will permit 3D analysis of dynamic cell processes such as embryonic development and the replication of viruses within cells. Orion will also have equipment available for intravital microscopy, in which cells are observed in vivo, permitting real-time analysis of disease progression in biosafety environments. Technologies that permit rapid analysis of large quantities of samples and data through image acquisition and high-throughput screening will also be available, adding agility to the research conducted at Orion.
Cryomicroscopy is a powerful tool for obtaining the structure of biological macromolecules with atomic resolution; this includes the architecture of cells, viruses, and protein complexes. Orion will have state-of-the-art transmission electron cryomicroscopes and detectors, as well as the full infrastructure necessary to prepare samples, making it possible to conduct in situ analysis of pathogen structures. These analyses will utilize electron cryotomography, a technique that can reveal details of cell superstructures as well as mechanisms of infection.
This beamline is specialized in low-energy X-ray computed tomography (soft X-rays). The instruments are designed to create quantitative three-dimensional maps with nanometric resolution of the structures and organelles in cells infected with high-risk pathogens. The name of this beamline is inspired by a large Brazilian tree and is also an acronym: Soft X-ray Bio-Imaging Beamline with Partially Coherent Illumination for Resolving Cellular Ultra-Structure in NAnometers
This beamline is dedicated to X-ray holotomography and operates at an intermediate energy range between the Sibipiruna and Hibisco beamlines. It will be used to produce three-dimensional nano-scale images in high resolution of tissues, organoids, and arthropods infected by dangerous pathogens. Its name is inspired by a plant known for its phytochemical and insect repellent properties, and is also an acronym for Tender X-ray Coherent IMaging Beamline for Ex-Vivo Small Animal Organs and Tissues
This beamline utilizes high-energy X-ray computed tomography for longitudinal studies on small animals infected with high-risk pathogens. The major differential of this beamline will be its capacity to generate images with millimetric resolution, roughly 100 times more detailed than conventional medical tomography, using a low dose of radiation. The beamline is named after a genus of plants with beautiful foliage and flowers and is also an acronym: HIgh-Energy Beamline for In-Vivo Small Animal COmputed Tomography.
CNPEM offers a program for training and qualification to work in high and maximum-level biosafety containment infrastructures (BSL-3 and BSL-4, respectively). This unprecedented initiative in Brazil is intended to train human resources in competencies that are still not widespread here and in other Latin American countries. The program includes theoretical activities and practical sessions held in a training laboratory that is a replica of real facilities inside a maximum containment biosafety facility (BSL-4), where routine safety protocols can be simulated without risk of infection or handling pathogens.
Orion is overseen by the Brazilian Center for Research in Energy and Materials (CNPEM), a private, non-profit organization supervised by the Ministry of Science, Technology, and Innovation (MCTI). The project is part of the federal government’s New Growth Acceleration Program (PAC), and is funded with resources from the National Scientific and Technological Development Fund (FNDCT/MCTI) and supported by the Ministry of Health (MS). This initiative is part of New Industry Brazil (Nova Indústria Brasil, NIB), an industrial policy to boost national development through 2033. Orion will serve as an instrument of national sovereignty, competence, and security in the fields of science and technology for research, defense, and human, animal, and environmental health. The creation of Orion is intended to strengthen the Health Economic-Industrial Complex (CEIS), an initiative coordinated by the Ministry of Health to meet priority needs from the Brazilian Unified Heath System (SUS).
The Orion project was named for the constellation and the three stars known as Orion’s Belt or the Three Marias which point toward the star Sirius, in a reference to Brazil’s electron accelerator. Like the stars of Orion’s Belt, Orion will have three beamlines connecting it to Sirius: Sibipiruna, Timbó, and Hibisco.
Orion will make it possible to safely conduct research on pathogens, cells, tissue, and organisms, permitting comprehension of biological phenomena related to the development of illnesses and potentially guiding the development of future diagnostic methods, vaccines, and treatments.
All of Orion’s structural, technical, and scientific apparatus will provide unrivaled conditions for investigating group 3 and 4 pathogens capable of causing severe and potentially transmittable diseases.
Various pathogens are included in the highest biological risk class (group 4) due to the risk they present to individual and collective health; Ebola is likely the best known of this group. In Brazil, one example is the Sabiá virus (SABV), a group 4 biological pathogen that causes a severe hemorrhagic fever. Although this virus was identified in Brazil, samples are stored abroad and cannot be studied domestically due to the lack of a maximum containment infrastructure. Alongside SABV there are other class 4 arenaviruses circulating in Latin America such as the Junín (which causes Argentinean hemorrhagic fever), Guanarito (the agent of Venezuelan hemorrhagic fever), and Machupo (the cause of Bolivian hemorrhagic fever) viruses.
Within the global context, other examples include the henipaviruses Hendra and Nipah which were recently identified in Australia and Malaysia, respectively. To deal with these infectious agents capable of causing severe and highly transmissible diseases, maximum biosafety containment facilities (BSL-4) like those planned for Orion are essential.
Above all, Orion will be an instrument of national sovereignty that will equip Brazil to prevent and face future health crises. Infrastructure of this type is essential for understanding the biology of high-risk pathogens in order to develop strategies for treatment and control and surveillance activities, for example.
The technical and scientific requirements of Project Orion were developed to meet a variety of needs ranging from strategic problems in public health to fundamental research in the areas of microbiology and infectology. On the right are some of the activities that will be possible at Orion, illustrating its versatility and strategic importance for advancing science, national sovereignty, and public health activities.
At Orion, researchers will be able to investigate infections transmitted by arthropod vectors such as mosquitoes and ticks. Studying the interactions between these vectors and pathogenic microorganisms can help develop more effective strategies to control the transmission of these diseases and manage outbreaks and epidemics, as in the case of dengue, chikungunya, yellow fever, and spotted fever
Basic research related to bacteria, viruses, fungi, and toxins forms the foundation of strategies to combat diseases and protect health. Advances on this front are key to understanding mechanisms of infection and spread of infectious agents, for example, pathogenicity mechanisms in disease hosts, characterization of molecular targets that can be used to develop treatments and vaccines, and discoveries of new microorganisms and toxins
Orion will offer different bioimaging techniques so that a single problem can be studied on various scales. When we look at pathogenic agents at the molecular level, we can reveal molecules or complexes of molecules that play a crucial role in infection or are essential for the replication of pathogens in the host. These molecular discoveries can support the development of new vaccines, medications, and diagnostic methods
When a suspicious sample is identified, health surveillance agencies take action to deal with the unknown agent or gather evidence. Manipulation, isolation, and characterization of samples of this nature begin in high or maximum biosafety containment environments to protect the health of humans and animals as well as the environment. This stage permits subsequent genetic sequencing, identification, and characterization of infectious agents, activities which can be performed in a level 1 or 2 facility
Before a vaccine or new therapeutic compound can be made available for use in humans, a series of previous tests are required by regulatory agencies. Pre-clinical trials confirm the safety, toxicity, and efficacy of these new vaccine or drug candidates, and are conducted in vitro and in experimental animal models
Biological agents are classified by health authorities according to different risk classes. Each risk class indicates the biosafety containment level (BSL) of laboratories dedicated to handling these biological agents, and may vary according to assessed risk . The different levels are abbreviated as BSL-1, BSL-2, BSL-3, and BSL-4, and each must meet rigorous international safety requirements. BSL-4 laboratories combine specialized and redundant safety measures intended to contain group 4 pathogens to protect those who work in these facilities, along with the community and the environment. Some of these measures are described below.
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The pandemic recently showed us the importance of technical mastery, suitable infrastructure, and qualified human resources in responding to public health challenges. Within this context, establishing a biosafety level 4 laboratory is strategic for the country and fulfills a long-standing demand from Brazil’s health and science professionals and institutions.
Although cases of disease caused by group 4 pathogens are a reality in various places around the world, including Brazil, few countries have the conditions to monitor, isolate, and research these biological agents, much less develop diagnostic methods, vaccines, or treatments. Without suitable infrastructure for advanced pathogen research, Brazil is dependent on other countries with BSL-4 labs, which affects national sovereignty when facing health crises related to group 4 pathogens.
The Sabiá virus (SABV) is one example of a pathogen identified in Brazil with recent case notifications that cannot be studied without a BSL-4 laboratory. Alongside SABV there are other arenaviruses circulating in Latin America that must be handled in this type of specialized infrastructure, such as the Junín, Guanarito, and Machupo viruses mentioned above.
The project is part of the federal government’s New Growth Acceleration Program (PAC) and funded with resources from the National Scientific and Technological Development Fund (FNDCT) and the Ministry of Science and Technology, with support from the Ministry of Health. This initiative is part of the federal government’s New Industry Brazil (NIB) stimulus policy and will serve as an instrument of national sovereignty, competence, and security in the fields of science and technology for research, defense, and human, animal, and environmental health. Orion was also planned to strengthen the Health Economic-Industrial Complex (CEIS), an initiative coordinated by the Ministry of Health and intended to meet priority demands from the Brazilian Unified Health System (SUS).
A fundamental aspect of what our experience with Sirius brings to Orion is the similarity of the technical solutions, which prioritize safety and reliability. Nationalizing the solutions and knowledge in planning the subsystems also benefits Project Orion by reducing installation costs, decreasing uncertainties, fostering innovation, and permitting more transparent, better planned, and safer operations. Sirius was the first large-scale, internationally competitive scientific facility constructed in Brazil, and the laboratory complex for advanced pathogen research will be built along the same lines.
Orion will span roughly 24,500 square meters, with various facilities and a new concept in the history of synchrotrons and biosafety research labs worldwide: a connection with three beamlines from the Sirius particle accelerator. Because of this connection, the project was named for the constellation with three stars that point toward the star known as Sirius. Besides the BSL-3 and BSL-4 laboratory facilities and research stations incorporating synchrotron light, Orion will also combine basic research laboratories, analytical techniques, and advanced competencies for biological imaging such as electron microscopy. All these scientific competencies together in the same complex will set it apart from all the other infrastructure available in Brazil and abroad.
The three new beamlines at Sirius (Hibisco, Timbó, and Sibipiruna) will be part of this expansive infrastructure dedicated to basic research, analytic techniques, and bioimaging planned at Orion. These three research stations with their respective synchrotron beamlines will allow scientists to obtain quantitative and qualitative data on the structure of systems infected with class 3 and 4 pathogens, from the subcellular up to the organism level. They will generate 3D images that will permit research ranging from studies of cells on a nanometric scale to the dynamics of inflammation in tissues and organ damage up to monitoring the infection process throughout the entire body.
Orion can also be seen as strategic for Brazil in terms of training a variety of human resources. Alongside the construction works and technological developments involved in the project, CNPEM also offers a national training program for high and maximum biological containment infrastructures that focuses on developing skills which are not yet widespread in Brazil and other Latin American countries.
This training program includes partnerships with international institutions that are references for Brazilian researchers working in BSL-4 laboratories abroad. It includes hands-on activities in simulated laboratory environments inside a mock-up laboratory at CNPEM without infectious materials or risk of contagion, under the supervision of professionals trained to assess the researchers’ individual skills in dealing with the conditions established in biosafety protocols.
Construction of the facilities will necessitate generation of related jobs and functions and circulation of information about the project, with ongoing communications between those who are directly involved and society at large. The design and construction stages will depend on highly qualified professionals who are able to understand the technical challenges that will arise. Later, the maintenance team will need to master critical protocols and procedures to safeguard the research teams so they can work in an appropriate and safe environment.
Later, research teams from across Brazil and foreign visitors will arrive, and they will not only be responsible for following the protocols and good practices required, but will also have an unequaled opportunity to access cutting-edge facilities that will allow extraordinary discoveries. Finally, teams in the areas of communications, management, and partnerships with public and private institutions will carry out their work as all these processes are underway.
Yes. Orion is intended to be available to researchers and institutions everywhere in order to respond to health challenges that affect Brazil as a whole. For this reason, the operating model has been discussed with various Brazilian research and health entities, along with researchers from the domestic and international scientific communities and public agencies such as the Ministry of Health. Research in an environment like Orion is very different than at Sirius. Analysis utilizing a synchrotron can be done relatively quickly, but research projects at Orion will require longer periods of time due to the nature of the samples involved; still, it will essentially be an open facility accessed through project proposals.
No. While access to Orion will have its own regulations established by a series of security procedures, it will operate independently and will not affect users or activities at the other facilities on the campus, or regular access to the Brazilian National Laboratories at CNPEM.
Yes. There are many examples of successful BSL-4 laboratories that are not located in wilderness environments, specifically because of the logistical importance of the selected location and the guarantee of the protective protocols. These examples include the traditional Robert Koch Institute, which is located within the city of Berlin and contains a BSL-4 laboratory on its grounds. The complex was officially inaugurated in 2015, and after testing phases it began regular operations in late 2018. Other examples of maximum biosafety containment laboratories in urban settings can be seen in the United States, such as the National Emerging Infectious Diseases Laboratories (NEIDL) facility affiliated with Boston University adjacent to its urban campus, the Centers for Disease Control and Prevention (CDC) in Atlanta, and the Integrated Research Facility (IRF) of the National Institute of Allergy and Infectious Diseases (NIAID) in Maryland.
Once the construction phase is complete, Orion will undergo technical and scientific commissioning and certification for international security standards in order to subsequently begin regular operations. The beamlines connecting Sirius to Orion will also undergo commissioning before they enter regular use in research projects involving pathogens of interest.
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