WHY BAT RESEARCH IS IMPORTANT

There is a lot to learn from bats – particularly because bats can carry viruses and not get sick themselves. This novel fact means that researchers can learn how to prevent the spread of viruses, understand what keeps bats healthy, and explore ways to keep humans and other animals safe from these very viruses. (See more about the remarkable clues bats hold.)

Scientists don’t know what protects bats from getting sick; that’s part of the question CSU’s research is trying to answer.

This is an important question and scientists are still working to fully understand the answer. This major gap in knowledge is one of the main reasons that CSU researches bats and the viruses they can carry.

There is some evidence that bats have a much more potent anti-viral response than humans, which may explain their resistance to these viruses. Although bats get infected, they almost never get sick. One exception is when they are infected with rabies virus, which kills bats.

Strangely, bats seem to make poor antibody responses to viruses compared to humans – this means that they don’t develop immunity to viruses like humans can. This might partly explain why viruses can circulate in bat populations – and that’s a key hypothesis that researchers are testing.

Research on what factors are important to bat health is a growing field that has important implications for how we treat diseases and viruses. Scientists need to study bats to find answers to these important questions. 

Better understanding how viruses and bats interact – in particular understanding how bats respond differently to some viruses when they are infected — can help us learn how we can proactively avoid viruses from spreading and treat animals and people when they are infected.

CSU’s research will help provide information and clues to all scientists who study how viruses spread between bats and other animals, as well as why bats can become infected with a virus but not become ill. This could lead to better ways to prevent virus spillover into humans, new treatments for human diseases, as well as help us understand how to better protect bats from diseases.

Bats play a critical role in controlling insects, pollinating plants, and spreading seeds.

Understanding how to keep bats healthy is important to our food systems and environment.

Millions of bats have died from white-nose syndrome, for example. CSU hopes to better understand bat immune systems and find new information that can help both people and bats.

There are more than 1,400 species of bats. Some bat species are sources of viruses that cause other animals or humans to become ill.

Unlike many other animals that can contract or carry viruses, bats hold special clues for scientists because they can carry a virus and spread it, but not get sick from it.

Examples of viruses bats may play a role in spreading include rabies, Marburg, Nipah and Hendra viruses. Bats – as well as other animals — also may carry and spread coronaviruses including MERS, SARS1 and SARS2. There are hundreds of SARS-related coronaviruses.

Very little is known about how bats transmit these viruses to other bats. And, in addition to the viruses we know about, there are probably many hundreds or thousands more bat viruses that we have yet to discover. 

People or animals may become infected by direct contact with feces, urine or saliva from a bat that is carrying a virus. Some viruses are transmitted from a bat to another animal first, then spill over into humans.  


ABOUT THE CSU BAT RESEARCH FACILITY

The new building was funded by a grant from the National Institutes of Health in 2021. CSU announced the grant and building plans.

A summary of the grant is available.

While the new facility that will be built at CSU will house some biosafety level 2 research, its primary function will be to provide an ideal space to breed virus-free, disease-free bats. These bats will be used at CSU for research and will be sent to other universities and government agencies for study.

At this time, there are very few scientists in the world studying bats and infectious diseases because there are extremely limited resources to obtain virus-free bats to use in studies. Generally, the only option is to capture them in the wild, which can disrupt their habitat and life cycles. 

Resources are limited because bats require specialized spaces mimicking their natural habitat to breed, this includes places to roost as well as with enough room to allow for free flight. There are only a handful of laboratories in the world that research bats because they cannot provide bats with proper habitats. CSU’s new building and veterinary expertise will fulfill this need and meets rigorous requirements for providing housing and habitat for bats.

This facility will be an important component to CSU research on bats and infectious disease — research that has been conducted for the last 15 years. It also will be an important national and international resource for research to look at pressing scientific questions about infectious disease and human and bat health.

In addition to focusing on infectious diseases and human and bat health, research can help scientists understand the biomechanics of flight, bat physiology and bat social structures.

Researchers will also focus on discoveries that could protect bats from diseases that threaten their existence, such as white-nose syndrome. White nose syndrome has killed millions of bats in North America and has recently been found in Colorado.

The facility is planned as a biosafety level two building, called a BSL-2. This is defined as a building where pathogens inside potentially present a “moderate risk” if accidentally inhaled, swallowed, or exposed to skin.

BSL-2 labs are common at research universities, private companies, and government agencies, and have safety requirements always in place. These include controlling access to the building or internal spaces, required personal protective equipment, using biological safety cabinets for research, and decontaminating all spaces as well as research tools, equipment and waste using heat or chemicals.

No pathogens requiring high containment laboratories will be used in the new bat facility, which will be a biosafety level 2 building, called BSL-2.

CSU has worked for years with SARS-CoV-2, MERS-CoV and others pathogens in its existing BSL-3 laboratory; the new building will be a BSL-2 (see more information under the biosafety section).

CSU does not work with viruses that require the highest level of laboratory containment, such as Ebola, Marburg or Nipah viruses, that require the use of a BSL-4 laboratory.

A group of bats is called a colony. Creating a colony within a facility takes years because bats are slow to reproduce; bats have one offspring once or twice a year. Bats also need specialized spaces to free fly, roost, and hide as they would in dark caves when sleeping, and otherwise behave like bats.

Establishing a colony of bats to be used in research within a specialized facility provides a population with known characteristics, such as their age and previous health status, and free of disease-causing microbes such as viruses – key factors in ensuring baseline data for research is consistent.

This also eliminates the disruption of habitats in the wild. If wild bats are used, researchers need to capture a significant number of bats to identify only a few with similar age, the same gender, that are virus-free, etc., to use in a single study. 

CSU uses as few bats as possible in studies, often as few as three or four bats in a single study. Some studies require as many as 20 or more; to use wild bats, scientists would need to capture many more than 20 to obtain a group of bats with the same characteristics for a study.


ABOUT CSU BAT-RELATED RESEARCH

CSU researchers have examined how certain viruses infect bats and have discovered that it is rare for most viruses to cause bats to become sick, with the exception of rabies virus.

Most mammals, including humans, have what’s called an inflammatory response when a virus enters their body and infects them. When a human is infected by a virus, even a simple flu virus, their inflammatory response helps them to create antibodies. Antibodies help to protect them from the same virus the next time – their bodies recognize the virus and trigger their immune system to respond to it.

This inflammatory response is generally the human response to a flu shot or other immunization, allowing people to build antibodies to fight the disease. If inflammation is too intense, however, it can cause death in humans.

This is one way in which bats and humans are different and allows an area for greater understanding. Bat inflammatory responses during infection are substantially less than what occurs in humans and could explain why bats rarely die from viral infections. It may also explain why bats typically don’t produce strong antibodies to viruses.

However, when bats are immunized against a virus, their immune system produces a better antibody response than it does when they are naturally infected by a virus, which can protect them from infection.

Future projects are expected to examine how coronaviruses, paramyxoviruses, and influenza viruses infect bats without making bats sick. Ultimately, this research will inform vaccine development, drug testing and how to prepare for pandemic threats.

Current CSU research is examining antibody responses in bats and whether innovative approaches to vaccinate wild bats may prevent viruses from spreading to other species. This is similar to how vaccinating wild raccoons and skunks against rabies has reduced rabies in these animals. 

Gain-of-function research is a class of research where an organism gains a new function. In some cases, gain-of-function research can be positive, such as grass being modified to be more tolerant to drought.

It is important that the term “gain-of-function” by itself covers a broad spectrum of types of research and research activities. Most recently, public and media discussion about “gain-of-function” has a much narrower meaning than the literal scientific definition. This narrow meaning is specifically related to a virus becoming easier to move between humans or becoming more lethal in humans.

When scientists and researchers discuss gain-of-function research, these conversations include a broader definition of activities that have been used for years as a strategy to conduct important research and help society – with a range of risks from extremely low- to high-risk activities. Critics of gain-of-function research and scientists agree that the potential outcomes of a subset of some activities related to gain-of-function research, particularly if there is not sufficient scientific oversight, may include the risk of creating organisms that are more transmissible or virulent than the original organism, such as a virus or bacteria. 

CSU has no plans to conduct gain-of-function infectious disease research with bats that could increase the transmission of a virus or other pathogens to humans.

Instead, CSU infectious disease research in university laboratories is focused on studying the fundamental response of a bat’s immune system to infectious pathogens, such as viruses as they already exist. This includes examining bats’ inflammatory responses when a virus is introduced into their systems.

CSU is not conducting research related to viruses and bats where there could be a risk of creating a new pathogen that would cause increased harm to humans.

Generally, CSU is enhancing its already strong oversight process into all of its research, including those that do not involve bats, to scan for a gain-of-function component and ensure that the research is carried out safely and to mitigate any potential risks.  

To learn more about gain-of-function research, consider reading this article https://theconversation.com/why-gain-of-function-research-matters-162493.

There are numerous categories of research that can be conducted to better understand and treat infectious diseases. CSU is planning to focus on understanding how bat immune systems respond to certain viruses and other threats.

Bats are generally not born naturally infected with viruses or diseases – they must be exposed to a virus, bacteria or other pathogen to carry that disease. There can be exceptions if the mother bat is infected with certain viruses; she may transmit the virus to her offspring.

Before CSU begins a research project on bats, we confirm the bats have not been naturally infected with and do not carry viruses. They are extensively screened for viruses using multiple methods including PCR, antibody testing and deep sequencing, which looks for the DNA  or RNA of a virus hundreds of times.

Once they are confirmed to be free of viruses, bats may be exposed virus or other pathogens as part of the research.

CSU researchers have been using bats in infection studies for more than 15 years. All of these studies have been performed in laboratories using best practices and procedures and in facilities that meet or exceed biosafety levels required for the research.  

Ebola, Marburg or Nipah viruses will not be studied in the new building or at any CSU laboratory. CSU does not and cannot possess these viruses. Our facilities are not built to research these viruses.

CSU may collaborate with researchers who study these viruses in laboratories located across the nation. This collaboration may include providing them with resources and expertise, but work with these viruses would not occur at CSU facilities.


BIOSAFETY AT CSU

Biosafety is the practice of developing precautions to lessen the risk of working with biological agents and animals exposed to infectious agents such as a virus.

Biosafety uses four principles to lessen risk.

  1. Work practices
  2. Personal protective equipment
  3. Facility design
  4. Administrative controls.

All of these work together in a layered fashion to protect researchers, their community, and the environment.

The CSU Biosafety Office identifies all risks for each experiment conducted at CSU. This office also determines the appropriate work practices, what personal protective equipment is required, the specific CSU facility where the work must be conducted based on layered biosafety within laboratories and buildings, and any additional practices or policies that are needed.

The personnel of this office have a combined 99 years of biosafety experience and have conducted research with biological agents themselves.

Multiple U.S. government agencies oversee bat and other infectious disease research at CSU, as well as university committees charged with overseeing research safety.

The U.S. National Institutes of Health Office of Laboratory Animal Welfare and the United States Department of Agriculture regulate and enforce oversight for animal welfare for all animal research at CSU.

Within the university, two separate, multi-disciplinary committees comprised of CSU researchers and experts, as well as community members who do not work for CSU also oversee bat research safety. These two committees are the Institutional Animal Care and Use Committee and the Institutional Biosafety Committee.

These committees review research proposals and procedures and hold researchers to federal and CSU standards, as well as ensure that animal research meets the highest ethical and safety standards. This ensures both the welfare of the animal as well as the researcher’s safety. CSU is a scientific pioneer in animal research ethics and welfare and was the academic home of the first animal bioethics expert in the world.

In addition, the CSU Biosafety Office provides additional internal oversight by working with researchers to determine how to implement and use best practices above and beyond state, federal and university requirements. This includes providing specialized training, choosing the correct personal protective equipment, developing standard operating procedures, preparing for emergencies and being ready to respond, and developing and following policies. In addition, biosafety experts periodically visit and inspect university laboratories.

Research laboratories are classified through a nationally-standardized system. Laboratory classifications are based upon the risks of the research being conducted inside the labs.

There are four primary biosafety levels for laboratories ranging from one to four, called BSL-1, BSL-2, BSL-3, and BSL-4.

A BSL-1 has safeguards in place, and the layers of protection increase with each classification. 

Layers of protection include special construction of the building, safeguards within the laboratory, special equipment, personnel protect equipment, and practices and procedures. The higher the BSL level, the more stringent the biosafety requirements.

BSL-1 is designed for working with organisms that are not known to cause disease and present minimal risk to the researchers and the environment.

BSL-2 is for work with infectious organisms that may make people sick but are easily treated.

An example of an infectious pathogen handled in a BSL-1 are some strains of E. coli and Bacillus subtilis.

Examples of infectious agents that are handled in BSL-2 labs are Streptococcus pyogenes, which causes strep throat, and Listeria monocytogenes and Salmonella cholerasesuis, which can be causes of foodborne illness, and some  seasonal influenza viruses. 

CSU researchers are required to receive extensive, specific training tailored to the viruses they research.

All researchers who work with viruses must pass multiple biosafety and biosecurity trainings corresponding to the risk of the viruses they will work with. They also receive training for specific procedures they will perform. 

In addition, researchers who work with viruses studied at CSU are required to train in responding to an emergency while working within the laboratory.

Researchers must be approved by CSU’s Institutional Animal Care and Use Committee if they are working with animals. Training must also meet multiple occupational health requirements.  This includes researchers demonstrating they have the appropriate experience and training to work with bats and are medically fit to perform their duties and wear all required personal protective equipment. 

In addition, CSU has an extensive focus on promoting and enhancing a research culture that takes extra measures to encourage compliance, reporting concerns, and training, so that there is not only an expectation that researchers follow the rules and respect protocols, there is a culture that encourages these practices.

The university and its researchers are routinely entrusted with national and international funds and research projects — in no small part because of our commitment to research safety. CSU requires rigorous and frequent accountability from its infectious disease researchers, as well as extensive training.

While there is no such thing as zero risk in research, the risk at CSU is extremely low.

Researchers are trained to report all potential risks right away to both their supervisors and the CSU Biosafety Office or the CSU Occupational Health program.

Research occurs within specially designed laboratories that are engineered specifically for the level of risk involved in the work being performed.

Some of CSU’s bat research takes place in a biosafety level three facility, called BSL-3.

The new bat research building at CSU is required to meet biosafety level two — called BSL-2 — precautions based on the research that will take place inside. However, CSU will exceed typical BSL-2 requirements for the new bat building. Biosafety measures for the new building will include:

  • Restricting entrance into the building itself.
  • Constructing the laboratory with multiple layers between labs where research takes place and the common spaces of the building.
  • Inside labs, work with infectious agents is performed inside of equipment designed to contain pathogens called biosafety cabinets. These cabinets are designed specifically to contain the infectious viruses during research and protect the researchers doing the work.
  • Researchers are required to wear specific personal protective equipment while working with viruses and infected animals.

CSU has procedures that assess the level of risk and that outline a response before research starts.

An incident can be defined as any accidental situation where there is a deviation from a standard operating research protocol that could present even the remotest possibility of risk. An example of a potential risk can be as simple as accidentally spilling liquid used in research on a counter in a laboratory.

If a researcher is potentially exposed or develops symptoms of a pathogen they work with, they immediately contact the CSU Biosafety Office, which is available at all hours. The CSU Biosafety Office works in conjunction with CSU Occupational Health to ensure the researcher is evaluated by local medical physicians, often physicians with a specialty in infectious disease. CSU also consults with national, state and local public health authorities.

The level of response and risk mitigation associated with a potential exposure is dependent on a wide variety of factors including the virus, bacteria or other infectious pathogen being worked with and whether the pathogen in use can be spread person-to-person.

An example of a response could include quarantining a researcher as well was monitoring for symptoms, testing for infection, and potential treatments.

CSU continuously strives to learn from other institutions to enhance our practices and procedures based on evolving best practices and potential biosafety enhancements.  

If an incident occurs, what matters is how researchers and an institution respond. That response is what mitigates risk to the researchers themselves, the community, and the environment.

CSU has developed a layered infrastructure to mitigate risks to as low as possible. This starts before our research laboratories are even built.

  • CSU follows required construction practices that include multiple layers of safety, ways to protect the environment, to building security that prevents outsiders from reaching a laboratory.
  • CSU uses special equipment designed for infectious disease research that keeps pathogens contained and protects the researchers from what they are working with.
  • CSU researchers are regularly trained on and follow very precise procedures that prevent a virus from getting on researchers, our clothing, or inside our bodies.

The physical structure of CSU’s laboratories as well as the procedures the university follows are constantly evolving and striving to be forward-thinking, use best practices and training methodologies, and keep our community safe.