We live in a dancing matrix of viruses; they dart, rather like bees, from organisms to organisms, from plant to insect to mammal to me and back again . . . passing around heredity as though (drugs) at a great party.
—Lewis Thomas
The Lives of a Cell
Microbiologists detected the existence of viruses in an indirect way before they were able to see them. The discovery begins in 1883 with Adolf Mayer, a German biologist who was investigating the cause of tobacco mosaic disease.
Tobacco-mosaic disease depresses the growth of tobacco plants and produces a mottled or mosaic coloration of the plants leaves. Mayer proved that the disease was infectious by transmitting it from plant to plant by spraying sap extracted from diseased leaves onto healthy plants. He searched for a bacterial microbe in the infectious sap, but he couldn’t find any. Mayer originally deduced that the disease was caused by an extremely small form of bacteria that could not be seen with the microscope.
Mayer’s small bacteria theory was tested ten years later by Dimitri Ivanowsky, a Russian who passed infective sap derived from infected tobacco leaves through a small pore filter designed to filter out bacteria. However, after the sap was passed through the filter it still produced mosaic disease.
In 1897 Martinus Beijerinck, a Dutch botanist, found that the infectious agent in the filtered sap could reproduce. Beijerinck sprayed tobacco plants with the filtered sap and found that after the exposure, these plants developed mosaic disease. He then used their sap and could infect more plants, and he continued this process through a series of infections. Beijerinck reasoned that the pathogen must be reproducing and increasing its numbers because its ability to cause mosaic disease was undiluted after multiple transfers from plant to plant.
It was then determined that the mosaic disease pathogen could reproduce only in the host organism, and it could not be grown in artificial nutrient media in test tubes or petri dishes. The pathogen could not be inactivated by alcohol, which is usually deadly for bacteria. Beijerinck correctly deduced that the reproducing particle must be smaller and more simple than bacteria. His beliefs were confirmed in 1935 by Wendell Stanley, an American biologist who crystallized the infectious particle now called the tobacco mosaic virus.
The History of Smallpox and Early Vaccination
The early practice called variolation to protect people from small pox has been used in cultures throughout human history and was common among African tribes. The concept of pre-exposure prophylaxis was first brought to colonial America by slaves. This practice of inoculation by placing the fluid from a “pox” sore from a person with smallpox into the skin of a healthy person was highly controversial in the colonies in the beginning of the 18th century. But it was soon widely adopted when it was documented that persons treated in this way generally had a mild case of the otherwise highly contagious and lethal disease with a 20-30 percent rate of mortality and could escape from the severe facial disfigurement the disease is known for.
According to historian Elizabeth Fenn in her book Pox Americana (published in 2001), the Western hemisphere was attacked by two smallpox pandemics just before and during the American Revolutionary War.
The smaller of the two pandemics is thought to have begun just outside of Boston in early 1774 and smoldered in that location for several years, killing an average of ten to thirty people per day. In Boston the Declaration of Independence was relegated to second place as an event of public interest behind a city-wide smallpox vaccination campaign.
The smallpox virus pandemic spread as far south as Georgia. It decimated the Tsalagi (the group of Native Americans often called the “Cherokee,” which is a slightly insulting term created by their historical enemies, members of the Creek Confederation) and the Haudenosaunee, the indigenous name for the six nations that made up what the Europeans named the Iroquois League). Both groups of Native Americans were allies of the British, and after the epidemic neither recovered sufficiently to fight the colonists successfully. Smallpox also derailed the British plan to raise an army of Black slaves and indentured servants with the promise of freedom after the war ended. The smallpox killed off almost all of the “Ethiopian regiment” as they were being recruited and trained.
Because of their relative isolation from Europe, the colonists were almost as susceptible to smallpox infection and death as the Native Americans. So many soldiers in the Continental Army fell ill during the epidemic that their leaders worried that smallpox would cause their revolt to grind to a halt.
“The small Pox! The small Pox!” John Adams wrote to his wife, Abigail. “What shall we do with it?” His concerns were quite correct; it was the virus, not the British army, that had stopped the Continental Army’s excursion into Quebec in 1776. Fenn noted, “One of George Washington’s most brilliant moves, was to inoculate the army against the smallpox virus, during the Valley Forge winter of 1778” Fenn went on to say, “Without inoculations, the smallpox epidemic could have easily handed the colonies back to the British.”
During his apprenticeship, Edward Jenner, a country physician overheard a local milk maid pass on a “folk belief” that as a milk maid she would never suffer the disfiguring facial scars of smallpox. She was excited because she believed she would never suffer from the typical scars of small pox because she already had contracted cowpox, a minor affliction common to dairy maids.
Years later, in 1796, Jenner collected pus from a cowpox lesion from the arm of a local milk maid and applied it to the skin of an eight year old boy. Eight weeks later Jenner exposed the boy to smallpox. The child remained well because cowpox was similar enough to smallpox to stimulate a cross-immunity.
According to Medicine: A Treasury of Art and Literature: “Jenner (1749–1823) possessed acute powers of observation that were usually spent bird-watching, and he gained admission to the Royal Society of London through a paper on ornithology. He noted that the bowed, broad back of a fledgling cuckoo for twelve days formed the perfect nest for the egg of the hedge sparrow, ready to hatch when the cuckoo was ready to fly. The story of the milk maid Sarah Nelmes and Jenner’s vaccine guinea pig, James Phipps is well known. Less familiar is Jenner’s attribution of cowpox to ‘grease’ and groomsmen.”
Over the next few years, Jenner published further experiments, supplying the cowpox “vaccine” and promoting his vaccination techniques to physicians around the world:
The deviation of man from the state in which he was originally placed by nature seems to have proved to him a prolific source of diseases. From the love of splendor, from the indulgence of luxury, and from his fondness for amusement he has familiarized himself with a great number of animals, which may not originally have been intended for his associates.
The wolf, disarmed of ferocity, is now pillowed in the lady’s lap. The cat, the little tiger of our island, whose natural home is the forest, is equally domesticated and caressed. The cow, the hog, the sheep, and the horse, are all, for a variety of purposes, brought under his care and dominion.
There is a disease to which the horse, from his state of domestication, is frequently subject. The farriers call it the “grease.” It is an inflammation and swelling in the heel, from which issues matter possessing properties of a very peculiar kind, which seems capable of generating disease in the human body (after it has undergone the modification which I shall presently speak of), which bears so strong a resemblance to the smallpox that I think it highly probable it may be the source of the disease.
In this dairy country a great number of cows are kept, and the office of milking is performed indiscriminately by men and maid servants. One of the former having been appointed to apply dressings to the heels of a horse affected with grease, and not paying due attention to cleanliness, incautiously bears his part in milking cows, with come particles of the infectious matter adhering to his fingers. When this is the case, it commonly happens that a disease is communicated to the cows, and from the cows to dairy maids, which spreads through the farm until the most of the cattle and domestics feel its unpleasant consequences. This disease has obtained the name of cow-pox. It appears on the nipples of the cows in the form of irregular pustules. At their first appearance they are commonly of a palish blue, or rather of a colour somewhat approaching to livid, and are surrounded by an erysipelous inflammation. These pustules, unless a timely remedy be applied, frequently degenerate into phagedenic ulcers, which prove extremely troublesome. The animals become indisposed, and the secretion of milk is much lessened. Inflamed spots now begin to appear on different parts of the hands of the domestics employed in milking, and sometimes on the wrists, which quickly run on to suppuration, first assuming the small vesications produced by a burn.
Most commonly they appear about the joints of the fingers and at their extremities; but whatever parts are affected, if the situation will admit, these superficial suppurations put on a circular form, with their edges more elevated than their centre, and of a colour distantly approaching to blue. Absorption takes place, and tumours appear in each axilla. The system becomes affected— the pulse is quickened; and shiverings, succeeded by heat, with general lassitude and pains about the loins and limbs, with vomiting, come on. The head is painful, and the patient is now and then even affected with delirium.
These symptoms, varying in their degrees of violence, generally continue from one day to three or four, leaving ulcerated sores about the hands, which, from the sensibility of the parts, are very troublesome, and commonly heal slowly, frequently becoming phagedenic, like those from whence they sprung. The lips, nostrils, eyelids, and other parts of the body are sometimes affected with sores; but these evidently arise from their being heedlessly rubbed or scratched with the patient’s infected fingers. No eruptions on the skin have followed the decline of the feverish symptoms in any instance that has come to my inspection, one only excepted, and in this case a very few appeared on the arms: they were very minute, of a vivid red colour, and soon died away without advancing to maturation; so that I cannot determine whether they had any connection with the preceding symptoms.
Thus the disease makes its progress from the horse to the nipple of the cow, and from the cow to the human subject.
Morbid matter of various kinds, when absorbed into the system, may produce effects in some degree similar; but what renders the cow-pox virus so extremely singular is that the person who has been thus affected is forever after secure from the infection of the smallpox; neither exposure to the variolous effluvia, nor the insertion of the matter into the skin, producing this distemper.
The more accurately to observe the progress of the infection I selected a healthy boy, about eight years old, for the purpose of inoculating for the cow pox. The matter was taken from a sore on the hand of a dairymaid, who was infected by her master’s cows, and it was inserted on the 14th day of May, 1796, into the arm of the boy by means of two superficial incisions, barely penetrating the cutis, each about an inch long.
On the seventh day he complained of uneasiness in the axilla and on the ninth he became a little chilly, lost his appetite, and had a slight headache. During the whole of this day he was perceptibly indisposed, and spent the night with some degree of restlessness, but on the day following he was perfectly well.
The appearance of these incisions in their progress to a state of maturation were much the same as when produced in a similar manner by variolous matter. The difference which I perceived was in the state of the limpid fluid arising from the action of the virus, which assumed rather a darker hue, and in that of the efflorescence spreading round the incisions, which had more of an erysipelatous look than we commonly perceive when variolous matter has been made use of in the same manner; but the whole died away (leaving on the inoculated parts scabs and subsequent eschars) without giving me or my patient the least trouble.
In order to ascertain whether the boy, after feeling so slight an affection of the system from the cow-pox virus, was secure from the contagion of the smallpox, he was inoculated the 1st of July following with variolousmatter, immediately taken from a pustule. Several slight punctures and incisions were made on both his arms, and the matter was carefully inserted, but no disease followed. The same appearances were observable on the arms as we commonly see when a patient has had variolous matter applied, after having either the cow-pox or smallpox. Several months afterwards he was again inoculated with variolous matter, but no sensible effect was produced on the constitution.
Vaccination with cowpox became mandatory in Bavaria, Denmark, and in Prussia and Britain in 1853. Some American states also began to require the vaccination with cowpox by mid-century.
Jenner’s vaccination concept was an important step toward reducing the global threat of infectious diseases. Vaccination made early childhood safer.
In the 1960s, worldwide health organizations promoted a campaign to eradicate smallpox epidemics. The last natural case of smallpox occurred in Somalia in 1977, and the World Health Assembly certified the eradication of smallpox in 1980.
Pasteur’s Remarkable Work on the Vaccine for Rabies
Louis Pasteur (1822–1895) was the first to connect alcoholic fermentation to the metabolism of yeast rather than “spontaneous generation;” however, it was his work with silk worm diseases, anthrax epidemics, and his high profile and widely publicized work with rabies that immortalized him. On March 1, 1886 Pasteur presented the promising results of his development of the treatment of a rabies vaccine for humans to the French Academy of Sciences and called for a creation of a rabies vaccine center, initiating the founding of the Pasteur Institute. His 1885 experiment to vaccinate humans with a vaccine created for dogs was a decision made at considerable legal risk and danger to his career:
We announced a positive advance in the study of rabies in the papers appearing under my own name and under the names of my fellow-workers; this was a method of prevention of the disease. The evidence was acceptable to the scientific mind, but had not been given practical demonstration. Accidents were liable to occur in its application.
Of twenty dogs treated, I could not render more than fifteen or sixteen refractory to rabies. Further, it was desirable, at the end of the treatment, to inoculate with a very virulent virus—a control virus—in order to confirm and reinforce the refractory condition. More than this, prudence demanded that the dogs should be kept under the observation during a period longer than the period of incubation of the disease produced by the direct inoculation of this last virus. Therefore, in order to be quite sure that the refractory state had been produced, it was sometimes necessary to wait three or four months. The application of the method would have been very much limited by these troublesome conditions.
Another objection was that the method did not lend itself easily to the emergency treatment rendered necessary by the accidental and unforeseen way in which bites are inflicted by rabid animals.
It was necessary, therefore, to discover, if possible, a more rapid method. Otherwise who would have the temerity, before this progress had been achieved, to make any experiment on man?
After making almost innumerable experiments, I have discovered a prophylactic method which is practical and prompt, and which has already in dogs afforded me results sufficiently numerous, certain and successful, to warrant my having confidence in its general applicability to all animals, and even to man himself.
This method depends essentially on the following facts:
The inoculation of the infective spinal cord of a dog suffering from ordinary rabies under the dura mater of a rabbit, always produces rabies after a period of incubation having a mean duration of about fifteen days.
If, by the above method of inoculation, the virus of the first rabbit is passed into a second, and that of the second into a third, and so on, in series, a more and more striking tendency is soon manifested towards a diminution of the duration of the incubation period of rabies in the rabbits successively inoculated.
After passing twenty or twenty-five times from rabbit to rabbit, inoculation periods of eight days are met with, and continue for another interval, during which the virus is passed twenty of twenty-five times from rabbit to rabbit. Then an incubation period of seven days is reached, which is encountered with striking regularity throughout a new series extending as far as the ninetieth animal. This at least is the number which I have reached at the present time, and the most that can be said is that a slight tendency is manifested towards an incubation period of a little less than seven days.
Experiments of this class, begun in November, 1882, have now lasted for three years without any break in the continuity of the series, and without our ever being obliged to have recourse to any other virus than that of the rabbits successfully dead of rabies. Consequently, nothing is easier than to have constantly at our disposal, over considerable intervals of time, a virus of rabies, quite pure, and always quite or very nearly identical. This is the central fact in the practical application of the method.
The virus of rabies at a constant degree of virulence is contained in the spinal cords of these rabbits throughout their whole extent.
If portions, a few centimeters long, are removed from these spinal cords with every possible precaution to preserve their purity, and are then suspended in dry air, the virulence slowly disappears, until at last, it entirely vanishes. The time within which this extinction of virulence is brought about varies a little with the thickness of the morsels of spinal cord, but chiefly it is related to the external temperature. The lower the environmental temperature the longer is the virulence preserved. These results constitute the central scientific point in the method.
These facts being established, a dog may be rendered refractory to rabies in a relatively short time in the following way: Every day morsels of fresh infective spinal cord from a rabbit which had died of rabies developed after an incubation of seven days, are suspended in a series of flasks, the air in which is kept dry by placing fragments of potash at the bottom of the flask. Every day also a dog is inoculated under the skin with a Pravaz syringe full of sterilized broth, in which a small fragment of one of the spinal cords has been broken up, commencing with a spinal cord far enough removed in order of time from the day of the operation to render it certain that the cord was not at all virulent. (This date had been ascertained by previous experiments.) On the following days the same operation is performed with more recent cords, separated from each other by an interval of two days, until at last, a very virulent cord, which has only been in the flask for two days, is used.
The dog has now been rendered refractory to rabies. It may be inoculated with the virus of rabies under the skin, or even after trephining, on the surface of the brain, without any subsequent development of rabies.
Never having once failed when using this method, I had in my possession fifty dogs, of all ages and of every race, refractory to rabies, when three individuals from Alsace unexpectedly presented themselves at my laboratory, on Monday the 6th of last July.
Theodore Vone, grocer of Meissengott, near Schlestadt, bitten in the arm July 4th by his own dog, which had gone mad.
Joseph Meister, aged 9 years, also bitten on July 4th at eight o’clock in the morning by the same dog. This child had been knocked over by the dog and presented numerous bites on the hands, legs, and thighs, some of them so deep as to render walking difficult. The principal bites had been cauterized at eight o’clock in the evening of July 4th, only twelve hours after the accident, with phenic acid, by Dr. Weber, of Ville.
The third person, who had not been bitten, was the mother of little Joseph Meister.
At the examination of the dog, after its death by the hand of its master, the stomach was found full of hay, straw, and scraps of wood. The dog was certainly rabid. Joseph Meister had been pulled out from under him covered with foam and blood.
M. Vone had some severe contusions on the arm, but he assured me that his shirt had not been pierced by the dog’s fangs. As he had nothing to fear, I told him that he could return to Alsace the same day, which he did. But I kept young Meister and his mother with me.
The weekly meeting of the Academie des Sciences took place on July 6th. At it I met our colleague Dr. Vulpian, to whom I related what had just happened. M. Vulpian, and Dr. Grancher, Professor in the Faculté de Médecine, had the goodness to come and see little Joseph Meister at once, and to take note of the condition and the number of his wounds. There were no less than fourteen.
The opinion of our learned colleague, and of Dr. Grancher, was that, owing to the severity and the number of the bites, Joseph Meister was almost certain to take rabies. I then communicated to M. Vulpian and to M. Grancher the new results which I had obtained from the study of rabies since the address which I had given at Copenhagen a year earlier.
The death of this child appearing to be inevitable, I decided, not without lively and sore anxiety, as may well be believed, to try upon Joseph Meister the method which I had found constantly successful with dogs. . . .
Consequently, on July 6th, at 8 o’clock in the evening, sixty hours after the bites on July 4th, and in the presence of Drs. Vupian and Grancher, young Meister was inoculated under a fold of skin raised in the right hypochondrium, with half a Pravaz syringeful of the spinal cord of a rabbit, which had died of rabies on June 21st. It had been preserved since then, that is to say, fifteen days in a flask of dry air.
In the following days fresh inoculations were made. I thus made thirteen inoculations, and prolonged the treatment to ten days. I shall say later on that a smaller number of inoculations would have been sufficient. But it will be understood how, in the first attempt, I would act with a very special circumspection . . .
On the last days, therefore, I had inoculated Joseph Meister with the most virulent virus of rabies, that namely, of the dog, reinforced by passing a great number of times from rabbit to rabbit, a virus which produces rabies after seven days incubation in these animals, after eight to ten days in dogs. . . .
Joseph Meister, therefore, has escaped, not only the rabies which would have been caused by the bites he received, but also the rabies with which I have inoculated him in order to test the immunity produced by the treatment, a rabies more virulent than ordinary canine rabies.
The final inoculation with very virulent virus has this further advantage in that it puts a period to the apprehensions which rise as to the consequences of the bites. If rabies could occur it would declare itself more quickly after a more virulent virus than after the virus of bites. Since the middle of August I have looked forward with confidence to the future good health of Joseph Meister. At the present time, three months and three weeks have elapsed since the attack and bites, his state of health leaves nothing to be desired . . ..
The Search for a Vaccine for Polio
In the mid–1800s, polio began to appear: in 1835 in the UK, in 1841 in Louisiana, in 1844 on the island of St. Helena, and between the 1880s and 1890s in Scandinavia. Through the next 50 years polio in its paralytic form spread through Europe and the United States.
The clinical path of polio was different than the epidemics of the plague, cholera, typhus, and typhoid fever. It killed few, but left many paralyzed and disabled. Polio was a new and confusing epidemic causing parents to keep their children inside rather than leaving them to play outside.
In 1908 polio was proven to be caused by a virus that primarily afflicted the central nervous system. By 1910, polio was recognized as a serious health threat. In 1916 the reports of polio increased by 400 percent. New York City alone reported 9,000 infected children that produced 2,343 deaths.
Investigations showed that before the 1980s children throughout the world had been infected with a mild non-paralytic strain of polio virus that produced an immunity to the more aggressive strains of the virus. By the early part of the 20th century public health projects in the industrialized world reduced the exposure to the polio virus by putting chlorine in public and private swimming pools and water supplies. These conditions produced the paradox that children coming from well-scrubbed middle class communities were more likely to be infected by the aggressive paralytic strains of the polio virus than those kids who were raised in less desireable, congested, and low income neighborhoods.
At the time, the standard method of viral propagation for vaccine production was in chicken eggs and non-human primates. Initially it was felt that a successful polio vaccine would require a recipe that contained more than one strain of the virus. A loose typing committee was formed that included both Jonas Salk and Albert Sabin to identify the various strains of the polio virus. Both Salk and Sabin were already working on polio vaccines. Salk was in favor of using killed viruses, and Sabin was in favor of employing attenuated or weakened virus.
In 1948, during one of the gatherings of the typing committee, Salk ventured to suggest that the public would be better served if the committee got on with producing vaccines and increasing the general population’s immunity to the virus rather than trying to understand the various strains of the polio virus:
I was suggesting that our purposes might be better served by testing an unknown virus’s capacity to immunize, rather than worrying about its capacity to infect. Albert Sabin sat back and turned to me and said, “Now, Dr. Salk, you should know better than to ask a question like that.’ It was like being kicked in the teeth. I had offered an oblique challenge to one of the assumptions, you see, and now I was being put in my place. I could feel the resistance and the hostility and the disapproval. I never attended a single one of those meetings afterward without that same feeling.
In 1948 John Enders, an American virologist working at Harvard University Medical School, developed a method for growing the polio virus in human cell cultures, which eliminated the need for non-human primates for vaccine production and of greater importence the cultured virus lost its capacity to produce the clinical form of polio. In 1954 Dr. Enders and two of his students, Thomas Weller and Frederick Robbins, were awarded the Nobel Prize in physiology and medicine.
The AIDS Epidemic
In the 1980s, the medical community recognized that “there was a new virus in town,” a new epidemic that destroyed the host’s immune system. Over a period of 20 years, 16 million humans perished from the infection and an additional 33 million had developed a chronic infection of what was soon to be identified as HIV, the human immunodeficiency virus that produced AIDS (Acquired Immunodeficiency Deficiency Syndrome).
On June 5th, 1981, the Centers for Disease Control (CDC), reported in its journal, Morbidity and Mortality Weekly Report, that five young male homosexuals had been diagnosed with a type of pneumonia usually associated with immune deficiency. A month later, the CDC published a follow-up report that described 26 cases of Kaposi’s sarcoma in 26 homosexually active males. These tumors were common occurrences in organ transplant patients being given immune suppressive drugs. By May 1985, 10,000 active cases of AIDS were reported. Most of the infected individuals died within two years after diagnosis.
The isolation of the HIV virus was reported in 1983 independently by two different laboratories which produced an ongoing war between the two laboratories for decades.
Robert Gallo, an American, was one of the discoverers. He worked for the National Cancer Institute which is a member organization of the National Institutes of Health referred to the controversy between the two groups as “an acrimonious controversy involving legal, moral, ethical, and societal questions that soon spilled over into the world of scientific research and threatened to poison relationships between scientists, as well as between the research community and the general public.”
Luc Montagnier, a respected member of the Pasteur Institute in Paris, who later became the director of the Center for Molecular and Cellular Biology at Queens College in New York, was Gallo’s scientific opponent.
It eventually was agreed upon by both the Gallo and the Montagnier camps that the AIDS virus was passed on through infected blood and body fluids. Gallo created a test to identify subclinical carriers of the AIDS virus, but the French group refused to use it as a screening test for the safety of transfused blood which resulted in the death of more than 300 hemophilia patients that had been given contaminated blood. These events led to criminal trials in France that resulted in the convictions and imprisonment of four heathcare employees.
Eventually, Jonas Salk, Peter Duesberg, Michigan Congressman John Dingell, the Office of Inspector General at the U.S Department of Health and Human Services, and various news reporters, including John Crewdson of the Chicago Tribune and Jon Cohen of Science magazine, jumped into the AIDS war.
While all of this controversy over the cause of AIDS, and who was going to get credit for isolating the virus and share in the royalties generated by the blood tests was grinding on, few if anyone recognized the breaking research of Dr. Will Taylor, associate professor in the Department of Medicinal Chemistry in the College of Pharmacy, from the University of Georgia at Athens, Georgia.
Through a detailed analysis of the genetic code of the human immunodeficiency virus (HIV), Dr. Taylor and his group discovered new viral genes. A translation of the genetic message in several of these genes showed that the proteins they encode have a requirement for the trace mineral selenium. Dr. Taylor’s analysis showed that one of these proteins could be a regulatory protein that acts as a master switch that would control the replication of HIV—a switch that could be regulated with selenium supplementation.
Dr. Taylor theorized that the supplementation of selenium could then slow the progression of AIDS, by reducing its replication rate and aggressive cell invasion. This would explain the long and highly variable latency period between HIV infection and AIDS, the declining selenium status of HIV-positive and AIDS patients, the route of transmission of HIV, and why some HIV-positive patients have never developed AIDS even after ten years.
Dr. Taylor demonstrated quite clearly that supplementation of the trace mineral selenium could prevent the HIV virus from mutating into clinical AIDS.
Over a ten-year period Dr. Gerhard Schrauzer spent great efforts to educate HIV and AIDS researchers of the potential benefits of selenium supplementation in HIV and AIDS patients. Schrauzer has published several arguments on the mechanism of how selenium could work on retroviral systems.