“The ultimate goal in virus hunting is an early warning system: to find a pathogen that could spark a disease outbreak before it has the chance to do so. The key, say scientists, is monitoring high-risk areas where animals and people intermingle.”
-Rene Ebersole, investigative journalist
“Most people stop looking when they find the proverbial needle in the haystack. I would continue looking to see if there were other needles.”
-Albert Einstein
In 1926, American microbiologist and writer Paul de Kruif published Microbe Hunters, a book that immediately became an international best seller and remains an inspiration for aspiring scientists and physicians. In the twelve chapters of his book, de Kruif tells the gripping stories of the brilliant discoverers of the microscopic world, not all of whom were scientists. For example, in chapter one, de Kruif writes about the Dutch cloth merchant Antonie van Leeuwenhoek who, as a side line, ground small magnifying lenses ultimately leading to his invention of the microscope. Using his invention, in 1674 van Leeuwenhoek was the first human to see bacteria; he was the first microbe hunter and is considered the father of microbiology.
Obviously, the technology to detect microscopic creatures has advanced enormously in the last three and a half centuries enabling us now to detect creatures as small as viruses (500 million rhinoviruses can fit on the head of a pin). This technology has led, in turn, to new brilliant microbe hunters making an increased number of amazing discoveries. In this Germ Gems post, I briefly review the strategies today’s microbe hunters use, especially those who are searching for the potential cause of the next pandemic.
Emerging infectious diseases (a recap). Over the past 50 years, approximately 140 microbes (bacteria, viruses, fungi, and parasites) emerged or reemerged that cause infectious diseases in humans. These so-called “emerging pathogens” were either new, such as HIV and SARS-CoV-2—the cause of COVID-19, or were previously known but widened their geographic range, such as West Nile virus and Zika virus.
About 70% of emerging pathogens are transmitted either directly or indirectly via insect vectors from animals to humans, that is they are zoonotic. Because of this, microbe hunters today operate as interdisciplinary teams that include scientists from both veterinary and human medicine, as well as microbiology, wildlife biology, and public health.
These interdisciplinary teams of microbe hunters have successfully determined how several devastating infections emerged. For example, they determined that dromedary camels are the reservoir of MERS-Co-V, the cause of Middle East Respiratory Syndrome that emerged in Saudi Arabia in 2012.
They have identified more than 700 cases of COVID-19 in animals—27 different species from 39 countries. They also determined that mink that caught SARS-CoV-2 in a spillback from humans now pose a significant risk of spillovers to humans. And in 2022, they confirmed mpox (monkeypox) virus in a pet dog—most likely a spillback from the pet owner.
Since the mid-1990s, microbe hunters have been tracking avian influenza A(H5N1) virus as a potential cause of the next pandemic. Since 1996, avian flu has devastated poultry flocks and wild bird populations (most recently Antarctic penguins) as well as a wide range of other animals including domestic cats in Poland and baby goats in Minnesota. As yet, influenza A(H5N1) has not spilled over in a big way to humans. (From January 2003 through December 2023, 883 cases of human A(H5N1) infection were reported from 23 countries—461 were fatal.) Nonetheless, many microbe hunters fear that once influenza A(H5N1) evolves a mechanism for easy transmission from person-to-person, it will be the start of the next pandemic.
Techniques for identifying microbes. In the 1970s, Carl Woese and his colleague George Fox published their discovery of archaebacteria (Arachaea) thereby showing that living organisms fall into three domains, not two. (Bacteria and Eukarya are the other two domains.) Woese’s discovery transformed our understanding of how living organisms evolved and how they are related. In addition, his work led to a new branch of microbiology, i.e., using gene sequence analysis to study natural microbial populations.
Today, scientists use Woese’s sequence analysis to identify and classify microorganisms according to their phylum, genus, and species designations. By combining, phylogenetic sequence analysis and polymerase chain reaction, they are able to identify microbes in samples from any source.
Technological advances led by Carl Woese fueled development of a new field of microbiology called metagenomics—the study of genetic material recovered directly from environmental samples. Environmental DNA (eDNA) is DNA that is collected from a variety of environmental samples, such as soil, seawater, sewage, snow, or air, rather than directly sampled from an individual organism. RNA may be abundantly excreted by organisms, and if sufficiently persistent in the environment, (eRNA) can be used to define the composition of the members of microbial communities .
In recent years, researchers have been routinely sampling wastewater and air in addition to probing clinical specimens, e.g., sputum, blood, urine, stool, etc. These modern day methods are proving increasingly productive in monitoring pandemics, such as COVID-19.
Viruses that infect humans. Throughout human history viruses have wreaked more havoc on mankind than any other group of pathogens. (Smallpox virus, for example, killed more people than all wars in history combined.) Hence, most modern day microbe hunters are searching for viruses that infect or could infect humans.
Viruses cannot survive on their own. Instead, they must get themselves into cells where they can multiply, using the host cell’s intracellular machinery to accomplish this task. To infect humans, an animal virus needs four properties. It must:
Use a receptor on human cells to gain entry;
Use human intracellular proteins to multiply and exit cells;
Evade human innate immune responses (phagocytes and NK cells); and
Bypass human adaptive immunity (antibodies and T cells).
Scientists today know where viruses capable of spawning pandemics are found, for example, many are in birds or bats. They also know how most viruses are transmitted. Armed with this enormous knowledge, there’s reason to be cautiously optimistic that future pandemics can be circumvented.
A new coalition for preventing viral pandemics. A new commission on the prevention of viral spillover is described in the article “The Lancet-PPATS Commission on Prevention of Viral Spillover: reducing the risk of pandemics through primary prevention” in the February 17, 2024 issue of The Lancet. The commission’s main focus is on emerging viral infections that have occurred due to spillovers, such as the five viral pandemics that unfolded from 1918 through 2009 (four due to influenza viruses and the fifth to HIV).
Recognizing that most efforts to prevent pandemics are now largely designed to contain the spread of viruses among humans after a spillover already has occurred, the void that this commission aims to fill is primary pandemic prevention—nipping emerging infections in the bud before spillovers occur.
The Lancet commission has recruited a highly talented transdisciplinary team of experts. But it’s not immediately apparent where the funding for the commission and its work will come from. As stated in the Lancet article, “Given the catastrophic societal impacts of viral emergence, governments, particularly those with greater resources, must urgently prioritize primary pandemic prevention.”
The science and the expertise are there to prevent the next pandemic. Let’s hope those responsible for funding recognize the need for prioritizing primary pandemic prevention and come forward with resources necessary to achieve this goal.
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