Museums in One Health

The majority of emerging infectious diseases are zoonotic in origin, and these disease events are becoming increasingly frequent (Jones et al., 2008). The impacts on economies and public health are being felt around the globe, and the devastating consequences of the recent Sars-CoV-2 pandemic demonstrate our continued inability to combat these spillover events effectively.

There are an estimated 1.67 million viruses that have yet to be discovered in wildlife and as many as half of those viruses could potentially infect humans (Carroll et al., 2018). The link between a virus and its host provides crucial information that allows researchers to better predict and mitigate spillover risk, such as: the host population size, range, and the geographic distribution (Grange et al., 2021). Understanding the evolutionary relationship between a host and virus can provide valuable insights into cellular interactions, changes in prevalence and distribution, and ecological factors that influence the likelihood of spillover into humans (Colella & McLean, 2020). Unfortunately, low disease prevalence would require the collection of large numbers of host samples (Plowright et al., 2019), often making the time and funding needed to pursue comprehensive field testing prohibitive.

Natural history museums with biorepositories can simplify the process and serve as valuable resources for understanding the ecology and evolutionary history of zoonotic diseases and their wildlife hosts (Dunnam et al., 2017b). Due to various constraints, it is not always feasible for museums to preserve and track specimens in a manner suitable to disease ecology research (Zimkus & Ford, 2014). This study surveyed institutions across the globe to identify geographic, temporal, and taxonomic gaps in museum specimen collections related to the preservation of viral genetic material. We focused on species within the most relevant orders Rodentia and Chiroptera, and our results will be used to guide a funded follow-up project testing specimens for betacoronaviruses.

With so many viruses in existence, prioritizing those most likely to cause zoonotic outbreaks is necessary. Coronaviridae is a diverse family of single-stranded RNA viruses (Anthony et al., 2017), and a higher percentage of RNA viruses are zoontoic (159 of 382, 41.6%) than DNA (29 of 205, 14.1%) viruses (Olival et al., 2017). Seven viruses in this family (two in the Alphacoronavirus and five in the Betacoronavirus genera) are known to infect humans (Becker et al., 2021). Three of these - SARS-CoV, SARS-CoV-2, and MERS-CoV - are highly pathonogenic and have resulted in large-scale pandemics in the past 25 years (Zhou et al., 2020). These viruses are prone to host switching (Anthony et al., 2017), have a high mutation rate, and have evolved RNA proofreading and repair mechanisms that help reduce the negative consequences of a high recombination rate in a large genome (Denison et al., 2011) - all features that make these viruses prime candidates to montior for spillover risk.

The term museum stems from the Greek mouseion, a temple to the 9 Muses of the arts and sciences, and it was originally used in reference to the Musaeum of Alexandria. Established in 3rd century B.C.E., the Musaeum of Alexandria and its legendary library were regarded as a place of scholarly excellence and intellectual fervor, and although the Musaeum disappeared a century after it was constructed, these connotations remained present when the word museum came into popular use in 18th century France (Young Lee, 1997). 

Many museums have maintained this legacy as pillars of scholarly pursuits, and collections-based research has spurred major changes in scientific thought from geography to evolution (Funk, 2018). Even within the world of disease ecology and One Health, the concept of forming beneficial parnterships with natural history museums is not entirely new. As early as 1909, the American Museum of Natural History recognized the potential of this collaboration and established their own Department of Public Health (Brown, 2014).

However, the real turning point in this collaboration occurred in 1993 when a mysterious virus caused 13 human fatalities in Southwestern America (Dunnum et al., 2017). Using specimens preserved at the Museum of Southwestern Biology, researchers discovered the hantavirus responsible for the deaths, determined the wildlife host to be deer mice, and uncovered evidence that the spillover into humans was connected to El Niño cycles. The inability of researchers to tap into this resource and identify the oringal host of SARS-CoV-2 is largely a result of the decreasing number and diversity of specimens from certain areas of the world that are accessible to scientists (Colella and McLean, 2020).

Relatively few in the One Health community embrace the value of leveraging existing biodiversity infrastructure (i.e., natural history collections, biorepositories, and their associated expertise and informatics resources) to more fully understand zoonotic pathogen emergence and reemergence. - Cook et al., 2020

There are over 3 billion specimens in natural history museums around the globe (Rogers, 2016). However, a majority of these are not preserved in a way that is suitable for disease research (Cook et al., 2020). Traditional collections focused on preservation involving skins, skeletons, and fluid-preserved specimens. Techniques in preservation began shifting in the 1970s, and continued to advance to meet the higher quality needs of DNA research. However, many methods capable of preserving host DNA will not prevent degradation of viral RNA. The current gold standard to preserve tissue samples and any viral RNA present is storage in vapor-phase liquid nitrogen freezers (-196°C) (Phillips et al., 2019). In addition to long-term storage requirements, the utility of a tissue sample for RNA research depends on the initial storage methods in the field as well as any changes during transport (Zimkus & Ford, 2014). For initial storage, the ideal method is to flash freeze in liquid nitrogen as soon as possible (Phillips et al., 2019) and freeze-thaw events should be avoided (Zimkus & Ford, 2014).

Due to various constraints, this is not always feasible and not all museum collections contain specimens preserved and tracked in a manner suitable to disease ecology research. Prior to 2014, there were no best-practice standards for the documentation and storage of genetic resources in natural history museums and the methods used varied greatly across collections (Zimkus & Ford, 2014). Moreover, the Systematic Collections Committee of the American Society of Mammalogists did not formally publish their standards and guidelines on genetic resource maintanence until 2019 (Phillips et al., 2019). Consensus regarding the standard requirements for these collections is a necessary starting point, but the myriad of benchmarks surrounding safety, security, space planning, documentation, funding, backup precautions etc. prevent most museums from housing specimens appropriate for RNA research.

Our goal is to determine which museums around the world have bat and/or rodent specimens that are suitably preserved to examine viral RNA so that we can identify geographic, temporal, and taxonomic gaps that exist in current collections. A comprehensive compendium of zoological collections does not exist, nor is there a searchable portal for all biorepositories around the globe (Funk, 2018). Therefore, we created a list of institutions that are likely to meet the above-mentioned criteria using data aggregators such as VertNet and Global Biodiversity Information Facility (GBIF) as well as relevant literature searches (e.g. Dunnum et al., 2017).

The data we intend to ask for include:

• hierarchical taxonomy and catalog number for each specimen in the orders Rodentia and Chiroptera
• date of collection (preferably as mm/dd/yyyy);
•  location where specimen was originally collected (preferably as decimal degrees);
• the type of sample (e.g. intact specimens, tissue samples, blood samples, skeletons, skins, etc.);
• how samples were initially preserved (e.g. 95% ethanol, Allprotect Tissue Reagent, Dimethylsulfoxide (DMSO), RNALater Stabilization Reagent, Flash frozen at -80 degrees celsius or below, etc.), and;
• how the samples are being stored long-term (e.g. general-purpose or laboratory freezers (-12°C to -30°C), liquid nitrogen cryovats (below -110°C), room temperature using preservative, ultracold freezers (-50°C to -86°C), etc.)

Our final list is shown below and includes 107 collections from 21 countries.

As the map above illustrates, the museums in Africa and Asia are significantly under-represented. While this does not mean that specimens from these regions are missing, we need to do additional research in these areas to determine if this gap is a result of the databases used, a lack of data sharing, a language barrier, or if there is actually an absense of museums with suitable specimens in these locations.

Initial research suggests that it is possible that there are not many museums that meet our criteria in these regions. An article based on research from Moscow State University found that Russia only recently began cryogenically preserving rare or endangered species compared to other countries, and the focus of these resources is in biotechnology. Many of the problems being encountered in Russia are not unique, and these include: disaggregation/disconnect between researchers and the research community at large, the lack of funding for maintenance of biocollections, weak legal regulations of bioresources that impedes international collabortation, the need for uniform protocols and a singular database of collections (Kamenski et al., 2016).

Western Asia, which spans 20 countries, has also been found to demonstrate a gap in bat research networks and published research on bat-virus interactions. The longevity of some bats along with their ability to fly have posed challenges related to collaboration with neighboring countries on research efforts and require long-term studies that have robust funding resilient to changes in governemnt priorities and funding availability (Phelps et al., 2019). Another study examining bat specimens in Mexico revealed taxonmic and spatial gaps and undersampling in area with the greatest potential threat (Zamora‐Gutierrez et al., 2019), indicating that even though we include six collections from Mexico, their collections may have gaps.

Even in the USA, specimen acquisition has been declining, threatening the value that museum collections could provide to disease research (From Malaney & Cook, 2018). Another hurdle encountered in this project has been a pervasive atmosphere of competition among scientists, which stems from a "publish or perish" mindset. Researchers must work together if we are going to prevent future outbreaks and mitigate other environmental challenges on the horizon. The One Health framework will help us to take a more holistic approach to tackling these issues, but also, the interdisciplinary nature could help transition our thinking away from data ownership towards data stewardship. The current health crisis has demonstrated an inability mobilize quickly and effectively in response to an emergency, underscoring the importance of making data collection standardized and easily accessible across fields. It is crucial that we learn from our mistakes and foster a culture of proactive collaboration before the next spillover event occurs.