It has been six months now since the pandemic has had me working from home. I have been privileged to be able to do this and the extra ten hours a week I am not driving to work has allowed me time to pursue this blog. US deaths to the SARS-COVID-2 virus could reach 200,000 by the end of this month with worldwide deaths closing in on 1 million. A simple ratio of deaths to confirmed cases reveals a death rate of about 3%. What is still unknown is the health damage to those that got the virus and recovered. The world economy in response has ground to a halt, every day I go out I see more shuttered stores. Last year there was an outbreak of Eastern Equine Encephalitis (EEE) in Southern New England. 12 people caught the virus, 8 of them children. (7) The death rate for EEE is 33% with the survivors having severe to mild neurological disorders. It is spread by mosquitoes. The virus is thought to have originated (jumped from horses) in 1956 in Florida. (8) I do not know of anyone disparagingly calling EEE the “Florida Flu” or say it was made in a lab by evil Floridians. Why the difference between this small but deadly outbreak and a major pandemic?
Amulet with verses from Song of Erra, Babylonian 800 BC-612 BC (17)
Epidemics are as old as human cities, the first recorded mention is between 1200 BC and 800 BC in Babylon, the song or poem of Erra, the god of plague. Some 36 versions have been found on clay tablets with some formed into amulets that were worn as an apotropaion, magical protection.
Different authors have had different interpretations of the meaning of the text from an allegory of war and violence to its religious and literary significance but I see a more literal meaning, an attempt to explain this scourge of civilization. (9)(10)(11)
Erra has seven demon companions or soldiers, the Divine Heptad, to help carry out his deeds. But he is happily asleep with his wife, the goat-headed goddess Mammi. The Heptad are bored and implores Eshem, Erra's assistant or servant, to wake him. When finally awake, he arms the Heptad and goes on a rampage with the intent of not only destroying all humans but upending the order of the cosmos. Only after a long debate with Eshem does he finally relent and go back to his palace. The basic gist of the debate is: spare some humans so you'll have something to kill, later on, the pure logic of the parasite.
Let's look at some terms. Plague is a great word but should probably only be used for the rat-borne illnesses that “plagued” Europe in the Middle Ages. I think pandemics should be applied only to what has happened to our now global civilization in the last 100+ years. Under this definition, we are in the third to the fifth pandemic. Flu (1918. 50 – 100 million dead), AIDS (1980. 32 million dead), and in addition two other world flu outbreaks in 1958 and 1969 (~ 1 million dead each.) I also like "outbreak" but I think "epidemic" is the winner.
The word epidemic comes from the Greek word epidemios. It first appears in Homer meaning a person returning to one's own country and later meant to mean a stranger who comes to live in your country and was used in the context of storms, rumor, fame, reputation, and civil war. Hyppocrates in the 5th century BC was the first to use the word in a medical sense meaning: “which circulates or propagates in a country.” He named his 7 volume work on medicine, Epidemics. Hyppocrates was the first to try to characterize disease in terms of environment, season, and geography. Thucydides near the end of the 5th Century BC describes the first historical account of an epidemic, the Plague of Athens, in his history of the Peloponnesian War. He uses the words “ruin”, “pain”, “evil” and “scourge” but it was translated into “plague.” (1) The term “epidemic” is meant to describe diseases from both bacteria and viruses. The first virus was discovered in 1892 by Dmitri Ivanovsky, Tobacco Mosaic Virus and in 1901, the first human disease virus was discovered, the Yellow Fever Virus.
While looking through offerings from the Santa Fe Institute (12) I found the book: Viruses as Complex Adaptive Systems by Richard Solé and Santiago F. Elena (2), two Spanish researchers. This short dense (mathematical) book answers many questions and introduces a research direction for the study of viruses.
A complex system is a set of dynamic elements that interact in an intricate and interconnected way. Complex Adaptive Systems (CAS) are complex systems that interact with each other in such a way that each system is changed by the other, they adapt as they interact, and they co-evolve. The complex systems do not have to be biological but much of the terminology is from biological systems. CAS studies are noteworthy for a cross-discipline approach and their use of computers and sometimes simple models to tease out results. Thus CAS is a fairly new research field that started in the 1980s. (3)
Viruses are found anywhere there is life, in the land, sea, and air. Sea viruses kill some 20% of the bacteria in the sea each year thus keeping the seas from becoming stagnant ponds. Viral proteins left over in an organism can become essential to evolution. The mammalian placenta is formed by one such viral protein. Bacteria can live deep inside the Earth's crust and even in the boiling pools of nuclear reactors. Recently, bacteria have been shown to survive in open space for three years outside the International Space Station. (13) Where ever there are bacteria there are also viruses.
The origin of viruses is still a mystery and the authors mention three possible theories:
Viruses were once small cells that parasitized large cells and lost the ability to reproduce.
Viruses evolved from pieces of DNA or RNA that escaped from cells.
Viruses co-evolved with cells from the very beginning. The proponents of this theory point to the fact that there is no evidence of the above processes happening now so if they did happen they must have happened before the creation of the first cell. There is a proposal that DNA evolved from RNA complexes trying to escape from RNA viruses.
Viruses can contain RNA or DNA and are typed by the size of their genome. The smallest viruses are just strands of RNA called virions that have no protein shell or capsid. The next in size is the RNA which represents most of the viruses that infect mammals and humans. Third, are viruses that contain DNA instead of RNA. In 1992 what was thought to be a new bacteria was discovered at the University of Leeds. In 2004 a paper in Science announced a new type of giant virus named Mimivirus. A bunch of larger and larger viruses was discovered and in 2014 the current largest was found named Pandoravirus. It has a genome as large as a Eukaryote parasite. These newfound viruses are so big that they have their own viruses! Even though these giants are viruses and need a host to replicate, other smaller viruses use their genomes to replicate. Ask most biologists today if viruses are alive and the answer would be no? Viruses hijack the cellular machinery as their only way to replicate. The authors would say yes.
Viruses hijack and use cells to replicate in a bewildering variety of ways.
What we think of a virus is just the viral particle wrapped in a shell. Would we think of a pollen grain or a spore as alive? When viruses take over a cell the cell becomes part of the viral machinery making millions of viral particles until it dies.
There are many examples of bacterial or fungal parasites that require their host to replicate.
The discovery of giant viruses may require that we completely change our thinking.
To me whether they are alive or not is merely semantic, they are certainly biological and part of life. Much more interesting to me is their size. Most bacteria are not less than 1 micron (1 millionth of a meter.) At a size below .6 microns (600 nanometers, 1 billionth of a meter) quantum effects begin to show up in matter. Some viral particles are as small as 17 nm with virions being even smaller. During the time that giant viruses were found, tiny bacteria, both free-living and parasitic in the 200 nm to 800 nm range were discovered. In central Utah is a forest of Populus tremuloides (Aspen.) Called Pando and covering 108 acres (.44 sq km) with each tree an interconnected single clone it is in the running for one of the largest and oldest (800,000 years) living organisms. Such are the orders of magnitude of life, by any definition.
Quasispecies (4)
Viruses mutate at such a fast rate that they form complexes of like but unlike versions called quasispecies. Viruses mutate at a rate near the edge of what is possible to survive. If they mutated any faster the number of errors would be so great that the virus would go extinct. It has been proposed that raising the mutation rate of a dangerous virus could be a form of treatment but I know of no group that has tried this. SARS-COVID-2 is an RNA virus and RNA viruses have a high mutation rate. Preliminary studies however suggest that the virus is mutating slower than normal. If one looks closely, it is really too early to tell as there are conflicting reports and many articles have yet to be peer-reviewed. (5)(14)(15)(16) Remember that viruses co-evolve with the host and a high mutation rate allows the virus to get past the host's defenses. The mutation rate is an important parameter in modeling an epidemic.
Infection rate is another important parameter. The infection rate is the average number of new hosts a host infects. If the infection rate is one or less, the virus goes extinct. SARS-COVID-2 has an infection rate of around 4.7 which is fairly high. Infection rate is a way to locally manage an epidemic but it requires extensive testing. The infection rate in Tucson got to be close to 12 in early August 2020 but has since gone down to 8.4, still way too high. The infection rate determines what portion of a population needs to be vaccinated. One of the reasons that measles has been so hard to eradicate is that measles has one of the highest know infection rates at 12 to 18. This requires that 100% need to be vaccinated, which has proven impossible. Unfortunately, the authors didn't give the formula for calculating the vaccination rate given the infection rate so I don't know about SARS-COVID-2 vaccination.
The life history of a virus is another set of important parameters. Does the virus use a vector to spread? A vector is a host that carries the virus but does not get infected itself. Is the virus a specialist or generalist in how many species it infects. What are the mechanisms of host jumping? Often, host jumping is accelerated by environmental factors like habitat loss or crowding, or any other form of stress on the original host. Also, is the virus a specialist or generalist in what cell types it infects in the host? The season can also be a factor. Finally, there is the age distribution, spatial distribution, and general health of the host. In ancient cities, most adults were fairly healthy because of high childhood mortality. In ancient Rome, it is estimated that a Roman woman had to have 8 to 10 children to allow 2 to reach maturity. Once a Roman citizen reached 30 they could be expected to live not much less than today. (18) Spatial distribution for humans means crowded cities are always hit first. Human transportation networks are major transmission routes, looking at data on just highway trips it is astounding how much Americans drive. Anecdotal evidence of the current pandemic looks like the virus does best in enclosed areas with circulating air, unfortunately where the modern human race spends most of its time. Gatherings outdoors such as beaches and parks don't seem as dangerous. Also, there has been little evidence that mass protests still happening all over the world are triggering local outbreaks. Masks do help. An interesting anomaly is why does central Africa have so few cases? Is it just weak infrastructure and reporting hiding the data or is there something else going on?
Another set of parameters that the authors fail to mention is morbidity rate and from a public health perspective, the hospitalization rate. As I mentioned before the world morbidity rate for SARS-COVID-2 is around 3%. Not good, the morbidity rate for the 1918 Influenza was 1.9% and at least 50 million people died. I can't find good data from hospitalizations or the extent of secondary problems in patients who have contracted the virus.
This little research project has helped me and I hope it has helped you. I don't pretend to be any kind of an expert but the compilation of any knowledge can be important. My hope is that inquiry will breed understanding and cooperation that will finally put Erra back to sleep.
Martin, Paul M.V., and Estelle Martin-Granel. “2,500-Year Evolution of the Term Epidemic.” Emerging Infectious Diseases 12, no. 6 (June 2006): 976–80. https://doi.org/10.3201/eid1206.051263.
Solé, Ricard, and Santiago, F Elena. Viruses as Complex Adaptive Systems. Princeton University Press, 2019. https://press.princeton.edu/books/paperback/9780691158846/viruses-as-complex-adaptive-systems.
Chan, Serena. “Complex Adaptive Systems,” 2001.
Johns Hopkins Center for Health Security. “SARS-CoV-2 Genetics,” April 16, 2020.
Sanjuán, Rafael, Miguel R. Nebot, Nicola Chirico, Louis M. Mansky, and Robert Belshaw. “Viral Mutation Rates.” Journal of Virology 84, no. 19 (October 1, 2010): 9733–48. https://doi.org/10.1128/JVI.00694-10.
Sah, Ranjit, Alfonso J. Rodriguez-Morales, Runa Jha, Daniel K. W. Chu, Haogao Gu, Malik Peiris, Anup Bastola, et al. “Complete Genome Sequence of a 2019 Novel Coronavirus (SARS-CoV-2) Strain Isolated in Nepal.” Microbiology Resource Announcements 9, no. 11 (March 12, 2020). https://doi.org/10.1128/MRA.00169-20.
Montalvo, Mayra. “Eastern Equine Encephalitis: Case Series in Southern New England.” Neurology. Accessed September 4, 2020. https://n.neurology.org/content/94/15_Supplement/4141.abstract.
Favorite, F. G. “Some Evidence of Local Origin of EEE Virus in Florida.” Mosquito News 20, no. 2 (1960): 87–92.
Machinist, Peter, and J. M. Sasson. “Rest and Violence in the Poem of Erra.” Journal of the American Oriental Society 103, no. 1 (1983): 221–26. https://doi.org/10.2307/601878.
George, Andrew. “The Poem of Erra and Ishum: A Babylonian Poet’s View of War.” ResearchGate, 2013. https://www.researchgate.net/publication/303824207_The_Poem_of_Erra_and_Ishum_A_Babylonian_Poet's_View_of_War.
Taylor, Kynthia. “The Erra Song: A Religious, Literary, and Comparative Analysis.” Harvard University, 2017.
Santa Fe Institute. “Santa Fe Institute.” Accessed September 5, 2020. https://www.santafe.edu/.
Levy, Max G. “Scientists Discover Exposed Bacteria Can Survive in Space for Years.” Smithsonian Magazine. Accessed September 5, 2020. https://www.smithsonianmag.com/science-nature/scientists-discover-exposed-bacteria-can-survive-space-years-180975660/.
Lemey, Philippe, Samuel Hong, Verity Hill, Guy Baele, Chiara Poletto, Vittoria Colizza, Áine O’Toole, et al. “Accommodating Individual Travel History, Global Mobility, and Unsampled Diversity in Phylogeography: A SARS-CoV-2 Case Study.” BioRxiv, June 23, 2020, 2020.06.22.165464. https://doi.org/10.1101/2020.06.22.165464.
Worobey, Michael, Jonathan Pekar, Brendan B. Larsen, Martha I. Nelson, Verity Hill, Jeffrey B. Joy, Andrew Rambaut, Marc A. Suchard, Joel O. Wertheim, and Philippe Lemey. “The Emergence of SARS-CoV-2 in Europe and the US.” BioRxiv, May 23, 2020. https://doi.org/10.1101/2020.05.21.109322.
Toyoshima, Yujiro, Kensaku Nemoto, Saki Matsumoto, Yusuke Nakamura, and Kazuma Kiyotani. “SARS-CoV-2 Genomic Variations Associated with Mortality Rate of COVID-19.” Journal of Human Genetics, July 22, 2020, 1–8. https://doi.org/10.1038/s10038-020-0808-9.
Wikipedia. Amulet Dating from 800BC-612BC Warding off Plague. Found in the City of Ashur, Neo-Assyrian Period. July 15, 2010. British Museum. https://commons.wikimedia.org/wiki/File:Amulet_to_ward_off_plague.jpg.
Beard, Mary. SPQR: A History of Ancient Rome. Profile Books, 2015.
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