Rosa Rubicondior: Malevolent Design - Why Did Bats Get a Better Immune System Than We Did?

Seba's short-tailed bat, Carollia perspicillata

By Desmodus - Own work, CC BY-SA 4.0, Link

Bat cells could aid in fighting humans’ most deadly diseases | WSU Insider | Washington State University

Creationists assert that humans are the special creation of their designer god, placing humanity at the pinnacle of 'creation'. Even those theists who accept the Theory of Evolution but believe it was guided by God with humans as the intended ultimate outcome, regard humanity as their deity's supreme achievement.

If this claim were accurate, it would be reasonable to expect humans to possess the optimal anatomical and physiological characteristics across all biological systems. In reality, numerous species exhibit superior traits and abilities compared to humans—traits which, had they been bestowed upon humans, would have significantly improved our wellbeing and survival capabilities.

For instance, birds have a respiratory system far superior to mammals, including humans, enabling efficient oxygen exchange during flight. Raptors possess remarkable eyesight, allowing them precise vision at speeds that would render nearby objects a mere blur to human vision. Elephants, sharks, and naked mole rats exhibit extraordinary resistance to cancer. Furthermore, many mammals experience lower perinatal mortality rates than humans even with modern medical intervention.

As highlighted in a recent study published in PLOS Biology, bats tolerate viral infections that are often fatal to humans, so they can harbour evolving viruses that, when they find their way into humans, can result in serious pandemics such as the recent COVID-19 pandemic.

If we entertain the creationist argument, their purported intelligent designer had already perfected these advantageous traits in other species. Yet, paradoxically, humans were deprived of these beneficial adaptations. This scenario suggests a designer whose decisions could only be interpreted as either incompetent or malevolent. It is the equivalent of a car manufacturer having designed a super-efficient, low-emission and cheap engine in one of its models, continuing to fit an old, expensive, wasteful and polluting engine to its top of the range model.

However, the evolutionary explanation — that different species evolved distinct traits adapted specifically to their environmental pressures — fully clarifies why humans possess adequate but not necessarily optimal traits. Unfortunately for creationists, adherence to their dogma forces them to dismiss this rational explanation, instead endorsing a narrative that inadvertently portrays their intelligent designer as either incompetent, malevolent, or potentially both.

That bats have superior immune system to humans has long been known, but why that is in terms of their cell physiology is still something of a mystery. Now, however, a team of researchers led by Washington State University molecular virologist Michael Letko has developed two lines of bat cell cultures which can be used to study how their immune system responds to different viruses, for example, the ebola virus, with a view to utilising that information to treat infections in humans.

Their findings are the subject of a research paper in PLOS Biology and are explained in a Washington State University (WSU) news item:

What is the current consensus on why bats have evolved such an efficient immune system? The current scientific consensus attributes bats' highly efficient immune systems primarily to their unique biological and ecological characteristics, especially flight. Several key hypotheses and supporting factors have been identified:

Flight and Metabolic Stress

Metabolic Hypothesis:
Flight is highly energy-intensive, generating significant metabolic stress. This leads to DNA damage and the production of reactive oxygen species (ROS). Bats appear to have evolved robust cellular repair mechanisms and anti-inflammatory immune responses to counteract this oxidative stress, inadvertently enhancing their immune function against pathogens.

Co-evolution with Viruses

Viral Reservoir Hypothesis:
Bats host a wide variety of viruses, many potentially lethal to other mammals, without apparent harm. This is thought to reflect a long evolutionary history of co-adaptation. Their immune systems evolved to control viral replication effectively without triggering harmful inflammatory responses, allowing bats to tolerate persistent viral infections without disease.

Reduced Inflammatory Response

Inflammation Regulation Hypothesis:
Unlike many other mammals, bats have evolved immune systems that respond efficiently but limit excessive inflammation. Chronic inflammation is damaging to tissues, and bats' ability to regulate inflammation prevents tissue damage even while managing viral loads. This controlled inflammatory response is central to their ability to coexist with viruses without significant health impacts.

Social Structure and Roosting Behaviour

Sociality Hypothesis:
Many bats live in dense colonies where pathogens can spread rapidly. The frequent exposure to pathogens in such environments may have driven evolutionary pressure for bats to develop stronger, more nuanced immune responses, particularly antiviral mechanisms.

Longevity and Cancer Resistance

Longevity Hypothesis:
Bats exhibit unusual longevity for their size, which generally correlates with enhanced cellular repair and robust immune function. Genes associated with longevity in bats overlap significantly with those involved in antiviral immunity and tumour suppression, suggesting an integrated evolutionary adaptation promoting both viral tolerance and long lifespan.

Consensus Summary:

The prevailing view integrates multiple hypotheses, emphasizing that bats' extraordinary immune capabilities evolved primarily due to selective pressures imposed by flight-related metabolic demands, the necessity to manage persistent viral infections without severe inflammation, their dense communal lifestyles, and longevity adaptations. This unique evolutionary convergence of physiological traits positions bats as valuable models for understanding disease resistance and immune regulation in mammals.

Bat cells could aid in fighting humans’ most deadly diseases
Why bats can harbor viruses like hantavirus and coronavirus – pathogens that are highly dangerous to humans – without becoming ill themselves has long puzzled scientists, yet the answer may be key to preventing outbreaks and fighting the diseases.
To help answer that question, a team led by Washington State University molecular virologist Michael Letko has developed two new bat-derived laboratory cell lines, providing much-needed tools for studying how bats and their immune systems respond to these viruses. The process for creating the new lines – which have been deposited with the American Type Culture Collection, a nonprofit repository for biological samples – can also importantly serve as a roadmap for creating additional lines to support future research. The research was outlined in the journal PLOS Biology.

Bats are a reservoir for many pathogens that can infect humans and domestic animals, yet we lack effective tools to study bat viruses in the lab. One big question is how do bats tolerate these infections? These cell lines and future research can help us uncover those mechanisms, and that could lead to new therapies for human diseases.

Assistant Professor Michael Letko, co-corresponding author
Paul G. Allen School for Global Health
Washington State University
Pullman, Washington, USA.

A cell line is a population of cells that are cultured and maintained in a laboratory for research purposes. These cells are typically derived from a single original cell and go through a process known as immortalization, which allows them to be grown and divided indefinitely under controlled conditions, making them a valuable tool for viral research.

While bat cell lines are critical for studying how these animals coexist with viruses, most labs have been limited to using the handful developed more than 50 years ago. Most viruses are species specific, and these lines come from species that often don’t respond to viruses of current interest, limiting their usefulness.

The new lines were developed from kidney tissue of a Seba’s short-tailed bat (Carollia perspicillata) that came from a colony maintained at WSU Vancouver by professor Christine Portfors.

The new lines support infection by a diverse group of viruses, but they will be particularly useful for studying coronaviruses and orthohantaviruses. The latter family includes sin nombre virus, which is found in the western United States and recently caused a fatal infection in Whitman County, Washington, the county in which WSU is located.

These viruses have the potential to impact not just our own national health, but global health, because they’re found all over.

Assistant Professor Michael Letko.

A major challenge to developing useful lines is ensuring the cells maintain their ability to mount immune responses to pathogens.

We started off with a pile of different tissues and cells, and then we went through different immortalization routes and basically started to weed them out. By the end, we had a small number of cells that were immortalized in specific ways, and those were the ones that actually still retained the properties we think are going to let us study how bats actually respond to viruses.

Assistant Professor Michael Letko.

Much research to date has relied on cell lines from humans, rodents or primates, which can’t answer why bats tolerate viruses that make other species sick.
We could study a virus like Ebola just fine in a human cell, and we can watch how it interacts with that immune system, but that won’t help us identify the reason why bats tolerate these infections.

Assistant Professor Michael Letko.

While some bat lines have been developed in private labs, those are not often made available to other researchers. Letko wanted to ensure their work would aid future research.

We have a lot of really good immunologists and virologists here and elsewhere, but they just don’t have access to all this specialized material. That creates tiers in bat research between the groups that have access and basically everybody else who had to rely on old cell lines that were collected in the 1960s.

Assistant Professor Michael Letko.

Abstract
Multiple viruses that are highly pathogenic in humans are known to have evolved in bats. How bats tolerate infection with these viruses, however, is poorly understood. As viruses engage in a wide range of interactions with their hosts, it is essential to study bat viruses in a system that resembles their natural environment like bat-derived in vitro cellular models. However, stable and accessible bat cell lines are not widely available for the broader scientific community. Here, we generated in vitro reagents for the Seba’s short-tailed bat (Carollia perspicillata), tested multiple methods of immortalization, and characterized their susceptibility to virus infection and response to immune stimulation. Using pseudotyped virus library and authentic virus infections, we show that these C. perspicillata cell lines derived from a diverse array of tissues are susceptible to viruses bearing the glycoprotein of numerous orthohantaviruses, including Andes and Hantaan virus and are also susceptible to live hantavirus infection. Furthermore, stimulation with synthetic double-stranded RNA prior to infection with vesicular stomatitis virus and Middle Eastern respiratory syndrome coronavirus induced a protective antiviral response, demonstrating the suitability of our cell lines to study the bat antiviral immune response. Taken together, the approaches outlined here will inform future efforts to develop in vitro tools for virology from non-model organisms and these C. perspicillata cell lines will enable studies on virus–host interactions in these bats.

Introduction
Most viral outbreaks in the last century have stemmed from cross-species transmission of viruses from wildlife to humans, often facilitated by domestic animals or hosts that may amplify the virus. For example, influenza viruses can spread to humans from birds and pigs, human immunodeficiency virus originated in chimpanzees, and hantaviruses spillover from rodents. Decades of wildlife surveillance efforts have revealed that bats can carry a wide range of viruses, including rabies, Marburg, henipaviruses, sarbecoviruses (subgenus of coronavirus) found across Asia, Africa, and Europe, and orthohantaviruses [1,2]. Since 2000, viruses similar to those found in bats have spilled over into the human population and has resulted in multiple, severe viral outbreaks, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the resulting COVID-19 pandemic.

Despite the increasing research interests in bats and the pathogens they carry, there is a significant lack of laboratory tools for these animals. One confounding factor is the enormous diversity of bats, with over 1,480 unique species spread across six continents [3]. The first bat cell line was derived from the lungs of an adult female Mexican free-tailed bat (Tadarida brasiliensis) in 1965 by Kiazeff and colleagues and was made available through the ATCC cell line collection that year [4]. In the 50 years since then, over 130 cell lines have been generated from 44 bat species; however, only 3 additional bat cell lines have been made publicly available to researchers (R05T, R06E, EfK3; S1 Table). Therefore, most bat species are understudied, leaving large knowledge gaps regarding how viruses transmit between bats and the animals they encounter. While some viruses are known to be carried by individual bat species, others are frequently shared between taxa [5]. Furthermore, comparative analyses show both variable and conserved components of bat immune pathways [6], which may suggest that bat-associated viruses may have evolved many mechanisms to evade the host immune response. As researchers discover novel viruses in bats, it is imperative that laboratory tools accommodate the growing need to study these viruses and their spillover potential.

Another challenge to developing bat laboratory resources includes the species-specific interactions that often occur between viruses and their hosts. While some viruses may be able to replicate in multiple species, most viruses, including those found in bats, are species-specific and do not replicate efficiently or at all with commonly available laboratory reagents. For instance, Hendra virus was observed to have higher infection efficiency in cells derived from its natural reservoir, the black flying fox (Pteropus alecto), compared to Nipah virus which is primarily found in the large flying fox (Pteropus vampyrus) [7]. Additionally, Ebolavirus and Marburg virus have similar replication kinetics in cells derived from the Egyptian fruit bat (Rousettus aegyptiacus), the natural host for Marburg virus [8]. Meanwhile, modeling of Ebolavirus infection in the Jamaican fruit bat (Artibeus jamaicensis) demonstrated systemic infection and oral shedding of the virus, but this was not observed for Marburg virus [8]. These studies emphasize the role of innate host factors and varied immune responses triggered in different bat species, where viruses may exploit or antagonize these responses in the bat species they have co-evolved with. Thus, to truly study how bat viruses interact with their natural reservoir hosts, it is essential to study these viruses in experimental systems that closely mimic their natural environments.

Development of antiviral drugs and therapeutics requires an intricate understanding of virus–host interactions, which can only be derived from laboratory experiments in either animal- or cell culture-based models. Here, we developed new bat cell lines and laboratory reagents from a panel of tissues from the Seba’s short-tailed bat (Carollia perspicillata). These cell lines were screened for their ability to support infection by a diverse panel of viruses representative of viral genera associated with this species, including alphacoronaviruses, betacoronaviruses, and orthohantaviruses [1]. These cell lines were further developed for routine mammalian cell culture and experiments to study bat viruses and innate immune responses. Our studies demonstrate that the resulting C. perspicillata cell lines are immunocompetent and mount a protective antiviral response upon double-stranded RNA (dsRNA) stimulation, making them suitable for future studies of bat-virus interactions and bat immunity. In addition, the kidney-derived cell lines are susceptible to a range of viruses, including Middle Eastern respiratory syndrome coronavirus (MERS-CoV), vesicular stomatitis virus (VSV), and orthohantaviruses. Notably, these cells support Andes orthohantavirus replication, which is closely related to other orthohantaviruses naturally found in these bats [9,10].

Gonzalez V, Word C, Guerra-Pilaquinga N, Mazinani M, Fawcett S, Portfors C, et al. (2025)
Expanding the bat toolbox: Carollia perspicillata bat cell lines and reagents enable the characterization of viral susceptibility and innate immune responses. PLoS Biol 23(4): e3003098. https://doi.org/10.1371/journal.pbio.3003098.

Copyright: © 2025 The authors.
Published by PLoS. Open access.
Reprinted under a Creative Commons Attribution 4.0 International license (CC BY 4.0)

Naturally, numerous additional examples exist in nature of 'designs' and biological processes significantly superior to those found in humans. These advantageous traits and capabilities could — and indeed would — have been bestowed upon humanity by an omnibenevolent, anthropophilic deity, had such a creator truly been responsible for our existence. The conspicuous absence of these optimal characteristics strongly suggests not only the absence of intelligent design behind human anatomy but also implies that the supposed creator god of creationism had no involvement whatsoever in shaping humanity.

In contrast, the well-supported and extensively evidenced Theory of Evolution clearly explains both the superficial illusion of purposeful design and the suboptimal compromises inherent in the anatomy and physiology of humans and all other species.

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