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Origin of Swine Flu and other Human Influenza Pandemics
Influenza is a highly contagious, acute illness in humans, pigs, birds, and other vertebrates (i.e., animals that have a backbone). Ribonucleic acid (RNA), not DNA (deoxyribonucleic acid) comprises the genetic material of influenza viruses, which belong to the family Orthomyxoviridae (orthos, Greek for “straight”’ myxa, Greek for “mucus,” and viridae, Greek for “virus”). The influenza virus comes in three genera: Influenzavirus A, Influenzavirus B, and Influenzavirus C. These three genera produce disease only in vertebrate hosts. Furthermore, Influenzavirus A is the cause of all flu pandemics in vertebrates, including the 2009 Mexican influenza global outbreak underway as of this writing. (1)
Influenza viruses are small (80 to 120 nanometers in diameter), pleomorphic (many shapes) particles that later become generally spherical. The core of an influenza virus contains the genetic information (RNA) of the virus, wrapped up in protein. The RNA consists of a long chain of “nucleotide” units (a nitrogenous base, a ribose sugar, and a phosphate). RNA is different from DNA in the following three ways: RNA usually boasts a single strand, whereas DNA has a double strand; RNA contains ribose, whereas DNA contains deoxyribose; and RNA has uracil in place of DNA’s thymine.
The genome of each influenza A virus consists of eight (8) distinct segments of single-stranded RNA. Each segment behaves like a mini-chromosome, meaning that each assembly of a new influenza virus requires one copy of each segment. Incorporation of RNA segments into progeny virions is at least partly random, notes Webster, et al. Indeed, “The random incorporation of RNA segments allows the generation of progeny viruses containing novel combinations of genes.” (2) Progeny cells that are simultaneously infected with two different parent viruses may “reassort” their individual RNA genomes to produce progeny with a new genome. The process of generating novel combinations of genes from two RNA viruses in the same parent cell and then passing the reassorted genome to progeny viruses is called “genetic reassortment.” For example, consider a person who is sick with avian influenza (H5N1) who also becomes infected by Mexican flu (novel H1N1, 2009). These two influenza viruses in the same human “container vessel” could potentially reassort their genes, producing a progeny virus that has a high virulence (like H5N1) and is easily transmissible from human to human (Mexican novel H1N1). This reassortment outcome would be very bad news for humans. The eight segments of influenza A viral RNA encode 10 recognized gene products, as follows Nucleocapsid is the term for the combination of RNA genetic material and accompanying protein inside an influenza virus. Overlying the nucleocapsid is a layer of matrix protein. Influenza A viruses are differentiated from type B and C influenza viruses on the basis of the identity of the major internal protein antigens—the nucleoprotein and matrix. An antigen is a substance that prompts the generation of antibodies and may cause an immune response. The purpose of the host organisms producing antibodies to viral hemagglutinin (HA) and neuraminidase (NA) is to induce protective immunity in the host. Covering the matrix protein is the viral envelope that the wily Influenza virus steals from the host cell membrane. The nucleocapsid and the matrix proteins become wrapped in cell membrane as they bud from the infected cell. The characteristic “spikes” of the influenza virus are surface membrane glycoproteins, called hemagglutinin (HA, or H), which are involved in attachment and fusion to the target host cell, e.g., respiratory tract or gastrointestinal tract cell lining. The glycoproteins radiate all over the surface of the virus. Clusters of neuraminidase (NA, or N), another membrane glycoprotein that enables newly formed virions to bud from infected cells, occasionally sprout from the surface of the virion. The genetic material inside the nucleocapsid controls the manifestation of surface membrane glycoproteins. The rapidly evolving hemagglutinin and neuraminidase glycoproteins are part of the reason virologists and vaccine makers continually adjust flu vaccines to the prevailing influenza strains every winter in the northern and southern hemispheres. (3) Hemagglutinin glycoprotein is an “the major surface antigen of the influenza virus virion…Owing to error-prone viral RNA polymerase activity, influenza virus HA is subject to a very high rate of mutation, estimated at about 2 x 10-3 base substitutions per position per virus generation, or about one base substitution in the HA gene per virus generation. Selection for amino acid substitutions is driven at least in part by immune pressure, as the HA is the major target of the host immune response,” note Webster, et al. (2) How many hemagglutinin and neuramidase glycoprotein subtypes (i.e., H1, H2,…and N1, N2,…) exist for influenza A viruses? Researchers currently recognize 15 antigenically distinct HA subtypes and 9 NA subtypes. Although viruses of relatively few subtype combinations have been isolated from humans and other mammalian species, all subtypes, in most combinations, have been isolated from birds. A zoonosis is a disease that is communicable among animals (here including humans) under natural conditions. Researchers do not know how many vertebrates are susceptible to influenza A, but they are sure of its existence in pigs, horses, humans, and birds. Examples of other zoonoses are salmonella, rabies, avian influenza (H5N1), SARS, Escherichia coli 0157:H7, anthrax, and tuberculosis, as described elsewhere. (5-12) During the 20th century, 4 antigenically different strains of influenza A virus in humans suddenly emerged, signaling an antigenic shift. The 4 times are: Each novel strain of influenza A noted above resulted in a pandemic. (12) The Mexican influenza virus currently causing a global outbreak of disease in humans may well be a fifth pandemic, i.e., In contrast to pandemics, epidemics occur between pandemics from gradual antigenic change in the prevalent virus, termed antigenic drift. (14) The 1957 “Asian flu” (H2N2) and 1968 “Hong Kong flu” (H3N2) caused debilitating human influenza pandemics witnessed by the late Martin M. Kaplan, DVM (1915-2004). Dr. Kaplan was an American veterinarian and virologist employed as chief of veterinary medicine and other positions by the World Health Organization in Geneva, Switzerland, beginning in 1949. He encouraged investigators to study influenza viruses in lower animals and birds to elucidate the origin of pandemic influenza viruses. (1,15) Roger Webster and other researchers responded to his challenge, publishing their work in the early 1990s.
All known influenza A viruses (H1 to H14 and N1 to N9) are perpetuated in aquatic birds, e.g., Canadian geese, note Webster, et al. Most birds “infected” with influenza virus are asymptomatic. The exceptions to this observation are a few strains of influenza virus, e.g., H5 and H7 subtypes, which produce systemic infection accompanied by central nervous system involvement, with death occurring within 1 week. In addition, influenza virus in ducks targets the gastrointestinal, not the pulmonary, tract. Webster writes: In wild ducks, influenza viruses replicate preferentially in the cells lining the intestinal tract, cause no disease signs, and are excreted in high concentrations in the feces…Avian influenza viruses have been isolated from freshly deposited fecal material and from unconcentrated lake water. This information indicates that waterfowl have a very efficient way to transmit viruses; i.e., via fecal material in the water supply. [Emphasis added] Furthermore, a large number of susceptible young ducks gather each year on Canadian lakes, where feces loaded with influenza particles are shed in the water. This fact explains the high incidence of virus infection in Canadian ducks, particularly juveniles. “Transmission by feces also provides a way for ducks, as they migrate through an area, to spread their viruses to other domestic and feral birds. (17) A vast influenza gene pool of every conceivable subtype exists among birds, concludes Webster, et al. (18) Influenza virus subtypes maintained in birds serve as a vast influenza sink for future mammalian pandemics.
Only H1N1 and H3N2 influenza A subtypes naturally exist in pig populations in the U.S. Influenza in swine was first observed in the United States during the catastrophic 1918 to 1919 human influenza pandemic. We know this because Richard Shope famously discovered in 1931 in retrospective serological studies in humans that the classic swine virus H1N1 was antigenically similar to the influenza A virus responsible for the 1918-1919 pandemic in humans. (19) This finding implied that swine influenza H1N1 had successfully “jumped” the species barrier from pigs into humans to cause the 1918-1919 pandemic. Classic H1N1 influenza viruses circulate at high frequency in swine herds in the north central U.S. An average incidence of 51% of hogs demonstrate antibody to H1N1. About 25% of the pig population in the total U.S. shows evidence via antibody titers of having had an infection with swine flu. (18,20) Swine flu vaccines are available for pigs; however, veterinarians must decide whether to vaccinate herds against influenza when the morbidity of swine flu among swine is low (e.g., nasal discharge, cough, fever). Pigs sick with the flu have 100% morbidity, but 0% mortality. (18,21) Outbreaks of influenza in swine in Europe, which is antigenically and genetically distinguishable from classic swine viruses isolated from swine in North America, are similar to H1N1 viruses isolated from ducks! Webster says, “The available evidence suggests that avian (H1N1) influenza viruses were transmitted to pigs and are causing significant disease.” (18) How do pigs catch avian influenza? Influenza in pigs is a respiratory disease. Therefore, they must be exposed to and inhale aerosolized bird feces containing live influenza viruses. Recall that most birds infected with influenza are asymptomatic and that the virus replicates in their gastrointestinal tracts from which it is expelled in feces, as noted above. One likely scenario is dust containing bird feces in turn containing live influenza viruses blown from an industrial bird farm, such as a chicken farm, into an industrial swine herd, where pigs inhale the particles. One observer notes, “if swine are indeed a source of any of the genomic segments of the new [Mexican] H1N1, industrial agriculture is by definition involved. Swine have long been identified as a mixing vessel in which avian and human strains reassort into new human-specific strains. And industrial pig production has squeezed out small farming, including across Mexico.” (22) Large pig and poultry operations are now concentrated in the same areas. Otto, et al, noted in 2007, “Over the past 60 years, the geographic distribution of both pig and poultry production in the U.S., for example, has become more clustered, with poultry production now being highly concentrated in the southeastern states and pig production concentrated in some of these same states, as well as in the Midwest. Similar trends have occurred worldwide with pig and poultry populations increasingly concentrated in particular locations which are often geographically coincident.” (22) Humans can “catch” classic swine influenza from swine. For example, 20% of slaughterhouse workers in one study had antibodies to swine influenza virus. (23) A good article describing the clinical history of two young men who developed mild, self-limited swine flu from exposure to swine is available elsewhere. (24) In addition, during 1976, swine influenza virus (H1N1) was isolated from military recruits at Fort Dix, New Jersey, as described elsewhere. (25-26) One recruit with the virus died after a day-long outdoor march, thereby triggering a massive government swine flu vaccination program that was terminated early because of the occurrence of Guillain Barre syndrome in an unacceptable number of vaccine recipients.
Now consider a pig ill with swine flu that becomes ill with avian flu—this situation is the perfect set up for reassortment of the segments of the two genomes with subsequent passage to progeny offspring. A human who inhales respiratory droplets from a pig with a certain character of reassorted genes in the influenza virions could theoretically become ill with a novel influenza that authorities have difficulty figuring out (the “fog of pandemic”). A novel influenza that is highly infectious among humans, but of low virulence (e.g., 2009 Mexican flu), is more desirable than one that is highly infectious and highly virulent (e.g., 1918-1919 Spanish flu). In sum, pigs serve as major reservoirs of H1N1 and H3N2 influenza influence viruses and are frequently involved in interspecies transmission of influenza viruses. “Although these strains have shown a limited capacity to spread from pigs to humans, their maintenance in pigs and the frequent introduction of new viruses from other species [e.g., birds] may be important in the generation of pandemic strains of human influenza,” conclude Webster, et al. (25) Birds are a reservoir of every conceivable subtype of influenza virus and are the “primordial” origin of pandemic influenza in humans, say Webster et al. However, where did the original influenza virus come from that infected the bird population? The late British astronomer/astrobiologist Sir Fred Hoyle and colleague Dr. N. Chandra Wickramasinghe propose that viruses and bacteria responsible for the infectious diseases of plants and animals arrive in the dust from space that continually bombards Earth. Furthermore, they argue, apart from their harmful effects, these same viruses and bacteria have been responsible in the past for the origin and evolution of life on the Earth. In their view, all aspects of the basic biochemistry of life come from outside the Earth, which is also the idea of panspermia. Hoyle and Wickramasinghe are part of a long line of ardent panspermists dating back to 4th century B.C. Greek philosopher Anaxagoras, as described elsewhere. (27-28) Wickramasinghe opines, “As new cases of bird flu continue to turn up at our doorstep, the appearance of streams of migrating birds in our autumn skies must fill us with a sense of foreboding…Flight paths that extend across thousands of miles, several billion migrating birds inhale and recycle large volumes of air at a height of about a kilometer above the ground. If the birds are incubating the dreaded H5N1 virus, it is possible that vast numbers of viral particles will be discharged into the atmosphere, some of which would serve to nucleate raindrops, others which rise in updrafts into the stratosphere and are carried around the world.” Planning for the next pandemic includes measures to minimize unprotected exposure to mist and weather, as soon as cases are detected in any locality. “The use of face masks could possibly reduce attack rates, as well as a general reduction of non-essential travel. It might also be profitable to explore the feasibility of deploying modern techniques of molecular biology to indentify viruses in the environment (air and rainwater samples), with a view to preparing vaccines ahead of major infective outbreaks. Such measures should of course to be considered in addition to the other precautions currently in train.” (27) Many people scoff at the ideas of Hoyle and Wickramasinghe, especially people who have not read their books and seriously considered their ideas. (27) The primordial origin of human pandemic influenza A virus appears to be the bird population, which acquired the virus from somewhere (panspermia?). Influenza A is a zoonosis, which means it is a disease that is communicable among animals (here including humans) under natural conditions. Birds, pigs, and humans are the biggest reservoirs of the influenza virus on Earth. Certain subtypes of influenza A seem to affect certain species more than other species. However, the various subtypes of influenza A have an uncanny ability to evolve, creating the nightmarish potential for “jumping” from one species to another species, with the undesirable potential outcome of causing a lethal human pandemic. The pandemic occurs because most humans have not before been exposed to the novel subtype. Notes:
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