Viruses–an Orientation

One of my readers asked if I would provide a basic orientation to the science of virology, a way of making viruses a little less mysterious than the “unseen enemy” featured on TV and in newspapers. I try to start at the beginning. I see viruses through the lens of the history of science. Seen that way, viruses are a part of story of how we see ourselves in the universe. That sounds ambitious, but bear with me.

The basic unit of life is the cell. People studying nature have seen, described, and studied cells since the mid-1600s, the early days of the light microscope (the optical instrument present in every junior high school science lab). Single-cell creatures, wee-beasties visible with the light microscope, i.e. bacteria, fungi, and protozoa, are nearly everywhere, once one looks. Bacteria, for example, are present on our skin, in our intestinal tracts, in pond water. In the 1600s the light microscope opened up a whole new world of inquiry and insight, much like early telescopes helped open up a new understanding of our place in the cosmos, and the study of fossils and atomic chemistry changed our understanding of time (for most of us). But I digress…

We tend to focus our attention on the wee-beasties that cause diseases in humans (and in our stock animals and crop plants). The single-celled organisms that cause anthrax, cholera, syphilis, malaria, tuberculosis, gonorrhea, leprosy, and african sleeping sickness (among others) were intensely studied in the 19th and early 20th century by researchers like Louis Pasteur, Robert Koch, Theobald Smith, and Walter Reed. All these people strove to find treatments or vaccines to rid humanity of these scourges. The stories of these scientists made news at the time, but today most of us barely recognize their names. Many physicians in “developed” countries like ours have never seen a patient suffering from leprosy, tuberculosis, malaria, or any of the diseases these researchers fought, diseases that had been part of life and literature for much of human history, 

Every disease mentioned above is caused by a single-cell creature that can be seen with the light microscope, but the light microscope, because of the physics of light itself, allows us to see organisms only as small as about 1 micrometer (µm). Contemplate that. Think of a millimeter (mm), the distance between two of the thinnest lines on the metric side of a modern ruler. Within that millimeter there are a thousand micrometers (µm) (aka “microns”). The world messured in micrometers (µm) is the domain of cellular life. For example, one phase of the malarial parasite, the “trophozoite phase”, is 1-2 micrometers (µm) in diameter. On the other end of the micrometer range are some free-living single-cell organisms like certain paramecia and amoebae whose size is between 250 and 750 micrometers (µm), one quarter to three quarters of a millimeter, a size visible to a young, healthy, naked human eye.

Cellular organisms, tiny as they are as members of the micrometer world, are still structurally complex. There is huge variation, but even the simplest bacteria contain genetic material (DNA, deoxyribonucleic acid), lipids (molecules of the material we generally call “fat”), and a variety of proteins. All of these organic molecules are organized in structures that provide cells the means to use chemical energy, energy to function and reproduce themselves, energy almost always ultimately traceable to the sun.

But what of the agents that cause smallpox, chickenpox, measles, mumps, polio or rabies? Scientists knew these disease organisms were smaller than known bacteria by running what now look like fairly simple experiments, but which, at the time, were revolutionary. By the early 1700s the word “virus” (originally “potent juice” in Latin) was applied broadly to any fluid from a diseased person that could infect another person. (At the time such fluid might have contained both viruses and bacteria.) In 1892 a Russian biologist, Dmitri Ivanovsky, used a filter developed by French scientists to filter out all the cells and bacteria from a fluid that could pass mosaic disease between tobacco plants. He went on to demonstrate that the remaining fluid was still infective. The filter removed everything which could be seen with the light microscope, the only tool then available at the time. 

A few researchers used the term “virus” to designate only the infective agent that passed through the filter, but through the first half of the 20th century the word was in common circulation to mean any infective fluid. (See P.S. below)

A new tool was needed before we could understand what the infective agent in this filtered fluid looked like. The first images of viral particles were made using early versions of the electron microscope in the 1930s. They were images of tobacco mosaic virus (TMV), the infective agent causing the mosaic disease mentioned above. A whole new sub-light-microscopic world opened up, a world measured in units of nanometers (nm), thousandths of a micrometer (µm). (Remember that micrometers, thousandths of millimeters, are used to measure the world of single cells, including bacteria.) Images of TMV particles obtained with the electron microscope show cylinders 300 nm in length and only 18 nm in diameter. Viruses are no longer “unseen.” SARS-CoV-2 particles are spheres measuring between 50 and 200 nanometers, i.e. a twentieth to a fifth of a micrometer. (The mammalian cells they infect and destroy range between 10 and 100 micrometers, 50-200 times the diameter of the virus.) 

In contrast to bacteria, which contain their own metabolic machinery, a virus is basically a protein and (sometimes) a lipid-encased blueprint for its own replication. (Coronavirus blueprints are encased in a lipid bilayer, think “fat”, hence their sensitivity to soap and alcohol.) Viral blueprints can be either RNA (ribonucleic acid) or DNA (deoxyribonucleic acid). (Coronaviruses are “RNA viruses.”) The details of the viral proteins that accompany the viral blueprint in a viral particle are essential for gaining access to the cells the viruses infect. Once inside the cell membrane or cell wall of the victim cell, the viral RNA (or viral DNA) hijacks the machinery of the cell to make countless copies of itself, weakening or destroying the infected cell in the process. (Netflix has a great verbal and visual explanation of this process, Coronavirus, Explained, you might find worth watching.)

I hope you find this as interesting to read as I have found it to review. For me, knowing some of the history of the scientific endeavor helps me understand how we know what we think we know (epistemology). It takes away some of the mystery with which some people seem to view science in general. Science is firmly rooted in observation and experimentation in the natural world. It consists of ideas that are testable and accretive. Understanding the basics upon which modern science rests is proof against those who see fit to make dangerous pronouncements based in deplorable ignorance as in a recent infamous example.

I give credit for this presentation to my parents and a long line of teachers, professors, and authors and to the volunteer editors of Wikipedia, front which much of what I present here was gleaned and suitably checked and cross-checked through its references.

Keep to the high ground,

P.S. What a word means changes over time. In doing the research for this article I wondered if the use of the word virus is different now from what it was when Paul de Kruif wrote the original Microbe Hunters in 1926, the book that engaged my mind with medical science as a youth. Sure enough. The original text of the book is available here. Searching the text for “virus” using CMD-F yields forty-three instances of the use of the word “virus” in de Kruif’s book. The very first use of the term–for the contagious material that causes cholera (a bacterium)–means that de Kruif used the word virus in the broad sense, i.e. any infective material, not just the nanometer-sized particles we label viruses today. No wonder I was confused in my youth. (Contemplate for a moment what this means for the interpretation of ancient texts that have gone through multiple translations…)

P.P.S. Among the many millions of viruses that co-inhabit our planet are a whole class of viruses called bacteriophages that infect bacteria. Think of that. Some bacteria that make us ill have their own viruses that infect them.

P.P.P.S. Note on Viruses and Atoms: The next “zone” smaller than nanometers (nm) are picometers (pm), one thousandth of a nanometer. This is the realm of atoms and parts of atoms. A typical atom is in the range of 100 picometers = one tenth of a nanometer. Think of the 18 nm diameter of the tobacco mosaic virus. Strung out along that 18 nm diameter line you might put roughly 180 atoms. In a 100 pm cross-sectional layer of that 18 nm diameter cylinder you might sandwich in 8085 atoms. (Think area of circle = π times r squared.It follows that in the entire 300 nm long cylinder of the tobacco mosaic virus you might fit around 8085 atoms/layer X 3000 .1nm thick layers = about 97 million atoms. Check my work. My math skills are rusty 🙂