Are viruses alive? Are viruses the fourth domain of life?

 

The word “virus” conjures up the terror of death on invisible wings. It raises images of hospital wards filled with patients dying of Spanish ’flu; poliomyelitis victims in iron lungs; health workers dressed in full-body suits against the deadly Ebola virus; or babies with microcephaly that could be linked to Zika virus. These are all dreadful human diseases, but they tell only a very small part of the story. Viruses infect all life forms—not just humans, and most viruses don’t even cause disease. Viruses are part of the history of life on Earth; precisely what part they play is a mystery that is slowly being unraveled.

The Oxford English Dictionary defines a virus as “an infective agent that typically consists of a nucleic acid molecule in a protein coat, is too small to be seen by light microscopy, and is able to multiply only within the living cells of a host.”

We think of germs as things that make us sick, and that includes both viruses and bacteria, so what’s the difference between bacteria and viruses? Bacteria, in common with other living cells, can generate their own energy, and translate the DNA sequences of their genes into proteins. Viruses can do neither.

Many important questions—some very fundamental— still remain open.

Are viruses alive? This question has plagued philosophers of science, though few virologists have tackled it. Some have explained that viruses are alive only when they are infecting a cell, and when they are outside a cell as an encapsidated particle, or “virion,” they are dormant, something like the spore of a bacterium or fungus. To answer this question, one first has to define life. Some argue that since viruses cannot generate their own energy, they are not alive. Whether or not we consider viruses to be alive, no one would dispute that they are an important part of life.

Are viruses the fourth domain of life? Darwin first conceived the idea of a tree of life, to reflect how organisms are related to each other. Since the 1970s life has been thought of as having three domains: bacterial, archaeal, and eukaryotic. The bacteria and the archaea each make up a kingdom of life, and the eukaryota are divided into several more: eukaryotes include animals such as ourselves, as well as plants, fungi, and algae. Bacteria and archaea are single-celled organisms that do not have a nucleus, and may be closer to the root of the tree of life. Eukaryotic cells are much larger and have distinct nuclei in which the genetic material resides and is replicated. Where do viruses fit on this “tree” of life? With recent discoveries of giant viruses, some proposed that viruses should be considered a separate domain of life. However, viruses can infect all other forms of life (including other viruses), and when we look at the genes that make up viruses and other organisms, we find that virus genes are everywhere, integrated into the genomes of all organisms. So rather than being a separate domain of life they are scattered throughout the tree.

Progress in the study of viruses accelerated in 1915 when one Frederick Twort discovered that bacteria, too, could be infected by viruses. Like many great discoveries, this was an accident. Twort was trying to figure out a way to grow vaccinia (cowpox virus), and he thought that bacteria might provide something essential for the virus to grow. He grew the bacteria in petri dishes, and in some of his cultures he found small areas that had become clear. No bacteria survived in these areas; something was killing them. Like the virologists before him, Twort showed that this agent could pass through very fine porcelain filters and infect and kill fresh cultures of bacteria.

Viruses teeter on the boundaries of what is considered life. On one hand, they contain the key elements that make up all living organisms: the nucleic acids, DNA or RNA (any given virus can only have one or the other). On the other hand, viruses lack the capacity to independently read and act upon the information contained within these nucleic acids.

Viruses live in a twilight zone, somewhere between life and its ingredients.

The different molecular strategies that viruses use to evolve within and between hosts, and to provide a view of the complexities of short term and long-term evolution, with their implications for viral disease.

Viruses exist in one of two general states, which you could think of as their ‘life’ cycle. In one state they are drifting around, either in solution or in the air, mainly just hanging around and ‘hoping’ to bump into the right sort of cell.

DNA viruses are likely to have co-evolved with their hosts while the DNA world was developing.

DNA virus evolution, includes the simplest and the most complex of the DNA viral genomes known.

Viroids are unique systems for the study of RNA structure, function, and evolution. They are the minimal RNA replicons characterized so far — their genome is 10-fold smaller than that of the smallest known viral RNA — and in a certain sense are at the frontier of life. Despite being exclusively composed by a single-stranded and highly structured circular RNA of only , viroids contain sufficient information to infect some host plants, to manipulate their gene expression for producing progeny, and, as a consequence, to incite in most cases specific diseases . In striking contrast to viruses, which encode proteins that mediate their own replication and movement, viroids depend essentially on host factors for these purposes and can therefore be regarded as parasites of their host transcription machinery

The detailed clinical features of five patients with COVID-19 are aligned with the quantitative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral RNA load from nasopharyngeal and other selected sampling sites. Previous studies in patients with SARS, Middle East respiratory syndrome (MERS), and COVID-19 generally provide insufficient detail to allow examination of the relationship between individual patient clinical course and viral RNA load.

Variation is intimately linked to their disease-causing potential. Paramount to the understanding of RNA viruses is the concept of quasispecies, first developed to describe the early replicons thought to be components of a primitive RNA world devoid of DNA or proteins.

Virologists now understand that virus populations are not made of a single member with a defined nucleic acid sequence. Rather, they are dynamic distributions of nonidentical but related members called a quasispecies. It was given this name because the classical definition of species – an interbreeding population of individuals – has little meaning for viruses.

The consequence of a quasispecies is that most viral infections are initiated not by a single virion, but a population of particles. The progeny produced after this infection results from selective forces that operate inside the infected host. The virions that go on to infect a new host have passed through another set of external selective forces. A steady-state population of a viral quasispecies consists of a vast number of particles.

Biology, and evolution in particular, are based on reproduction or multiplication and on variation. Reproduction; pure has the property of self-enhancement and leads to exponential growth. Self-enhancement in chemical reactions under isothermal conditions is tantamount to auto catalysis.

Nevertheless, based on the assumption that viral RNA load correlates with high levels of viral replication, there are important insights to be gained from this time-course analysis. Currently, our understanding of the relationship between viral RNA load kinetics and disease severity in patients with COVID-19 remains fragmented. Patients with COVID-19 with more severe disease requiring intensive care unit admission had high viral RNA loads at 10 days and beyond, after symptom onset. Unfortunately, it is unknown when in the course of their disease these patients deteriorated. Patients who developed late respiratory deterioration despite the disappearance of nasopharyngeal viral RNA. It would be interesting to know whether viral RNA load in lung tissue, or a surrogate sample such as tracheal aspirate, mirrors the decline in nasopharyngeal shedding. Nevertheless, this observation suggests that these late, severe manifestations might be immunologically mediated and has obvious implications for the potential to use immune-modulatory therapies for this subset of patients. This finding is consistent with recent reports that corticosteroids were beneficial for acute respiratory distress syndrome, and possibly those with COVID-19. With more detailed data such as those provided by Lescure and colleagues, the use of viral RNA load to suggest potential clinical strategies to treat COVID-19 could be exploited.

In the recent weeks of the surge in cases, one of the most peculiar and constant query has been about those who have COVID-19 symptoms but continue to test negative in RT-PCR tests. Sometimes, even though CT scan reports display patches in lungs due to coronavirus, the RT-PCR test report remains negative. According to experts, RT-PCR is the gold standard for COVID detection, however, as per reports from across the country, at least 1 in 5 patients may end up getting a false negative report. Why is that happening?

Even though RT-PCR is gold standard, we have known from Day 1 that there’s a 30 per cent chance of it to be inaccurate. Moreover, when the testing kits are developed, the scientists pick up those parts of virus which are least prone to mutate, therefore this could be a reason behind the false-negatives.

 The second reason for this could be that the viral load in your body is so less that its not getting detected in the RT-PCR test, as per experts.

The sample collection, transportation as well as the overburden of the cases, wherein the labs are not able to complete the analysis of the sample, plays a major role in the quality of tests, Dr Mahajan explained.

Next, repeat your RT-PCR test in 2-3 days, and take advise of your doctor to get a CT scan, says Dr Ray.

Blood tests at times are a good marker of inflammation and they can also give you and your doctor an idea of what is going on in your body, in particular, the C-reactive protein and the D dimer. Both of them are said to be a good testing ground for understanding what is happening in your body.

SARS-CoV-2 remained viable in aerosols throughout the duration of in  experiments (3 hours), with a reduction in infectious titer from 103.5 to 102.7 TCID50 per litre of air. This reduction was similar to that observed with SARS-CoV-1, from 104.3 to 103.5 TCID50 per millilitre. 

SARS-CoV, which causes severe acute respiratory syndrome (SARS). The incubation period for SARS is usually 2 to 7 days trusted Source, but it can be up to 10 days in some people.

MERS-CoV, which causes Middle East respiratory syndrome (MERS). The incubation period for MERS-CoV is between 2 and 14 days trusted Source, with 5 to 6 days being average.

The bottom line

Most people who develop COVID-19 start noticing symptoms within 2 to 14 days after being exposed to the novel coronavirus known as SARS-CoV-2. On average, it takes about 5 days to develop symptoms, but this may change as we learn more about the virus.

It would be interesting to know whether viral RNA load in lung tissue, or a surrogate sample such as tracheal aspirate, mirrors the decline in nasopharyngeal shedding. Nevertheless, this observation suggests that these late, severe manifestations might be immunologically mediated and has obvious implications for the potential to use immune-modulatory therapies for this subset of patients.

In a pandemic, prevention of disease transmission is key. 

It has been noted implications for transmission from patients with few symptoms but high viral RNA load in the nasopharynx early in the course of disease.

This finding is consistent with recent reports that corticosteroids were beneficial for acute respiratory distress syndrome, and possibly those with COVID-19. With more detailed data such as those provided by Lescure and colleagues, the use of viral RNA load to suggest potential clinical strategies to treat COVID-19 could be exploited.

It is noteworthy that the presence of viral RNA in specimens does not always correlate with viral transmissibility. In a ferret model of H1N1 infection, the loss of viral culture positivity but not the absence of viral RNA coincided with the end of the infectious period. In fact, real-time reverse transcriptase PCR results remained positive 6–8 days after the loss of transmissibility. For SARS coronavirus, viral RNA is detectable in the respiratory secretions and stools of some patients after onset of illness for more than 1 month, but live virus could not be detected by culture after week 3.The inability to differentiate between infective and non-infective (dead or antibody-neutralised) viruses remains a major limitation of nucleic acid detection. Despite this limitation, given the difficulties in culturing live virus from clinical specimens during a pandemic, using viral RNA load as a surrogate remains plausible for generating clinical hypotheses.

Virus crystals add a bit of disorder, and they will “wake up” and regain their infectious properties.

The process of transformation of viral components into organized solid particles is known as crystallization. A virus crystal consists of many thousand viruses and because of it’s purity we can understand their characteristics, pathogenic activity, mutational levels, nucleic acids, capsid properties.

Viruses sit on a fine line of what constitutes life. To some extent, the discussion is philosophical in that definitions are chosen and the subject either meets those criteria or not, and some criteria are a bit more arbitrary than others.

Some have argued that viruses in infectious virion form are life, at the stage when infecting a cell and redirecting its machinery to make more virus particles. 

Over the decades, biology has shifted from a study of cells in Petri dishes, or monks growing peas, to a more abstracted investigation into information science and related fields and subjects: mathematics, entropy, statistics, physics. That perspective started with scientists like Schrödinger, Turing, and Von Neumann, and it continues in the modern day with work by Dawkins, England, and others.

Viruses have and continue to shape the evolution of life around them. In a way, they are frozen information, and the definition of life may be changed over time, as we gain a more broader picture of how things work.

 Martinus Beijerinck while investigating the tobacco mosaic disease discovered a contagion. 

Unlike his colleagues, many of whom believed a bacteria would emerge as the cause, Beijerinck concluded that a new form of life must cause tobacco mosaic disease. He named this new organism the virus, a Latin word referring to poison. The word virus had been around since the fourteenth century, but his use was the first to link it to the microbes to which it refers today. Interestingly, Beijerinck referred to viruses as “contagium vivium fluidum,” or “soluble living agent,” and felt they were likely fluid in nature. That is why he used the term virus—or poison—to denote its “fluidity.” It wasn’t until later work with the polio and foot-and-mouth-disease viruses that the particulate nature of viruses was confirmed.

To learn to envision the world from the perspective of a virus. In order to understand viruses and other microbes, including how they cause pandemics, we need to first understand them on their own terms.

Viruses consist of two basic components, their genetic material—either RNA or DNA—and a protein coat that protects their genes. Because viruses don’t have the mechanisms to grow or reproduce on their own, they are dependent on the cells they infect. In fact, viruses must infect cell-based life forms in order to survive. Viruses infect their host cells, whether they are bacterial or human, through the use of a biological lock-and-key system. The protein coat of each virus includes molecular “keys” that match a molecular “lock” (actually called a receptor) on the wall of a targeted host cell. Once the virus’s key finds a matching cellular lock, the door to that cell’s machinery is opened. The virus then hijacks the machinery of that host cell to grow and propagate itself.

We can roughly divide known life on Earth into two groups: noncellular life and cellular life. The major known players in the noncellular game are viruses. The dominant cellular life forms on Earth are the prokaryotes, which include bacteria and their cousins, the archaea. These life forms have lived for at least 3.5 billion years.

Though often thought of as a pesky irritant or blight, viruses actually serve a role that goes far beyond, and has a much greater impact than, what was previously understood—a role that scientists are only just beginning to comprehend.

It’s true that in order to complete their life cycle, viruses have to infect cellular forms of life, but their role is not necessarily destructive or harmful. Like any major component of the global ecosystem, viruses play a vital role in maintaining global equilibrium. The 20 to 40 percent of bacteria in marine ecosystems that viruses kill every day, for example, serves a vital function in the resulting release of organic matter, in the form of amino acids, carbon, and nitrogen. And though studies in this area are few, it is largely believed that viruses, in any given ecosystem, play the role of “trust busters”—helping to ensure that no one bacterial species becomes too dominant—thereby facilitating diversity.

Viruses infect all known groups of cellular life. Whether a bacterium living in the high-pressure depths of the planet’s upper crust or a cell in a human liver, for a virus, each is just a place to live and produce offspring. From the perspective of viruses and other microbes, our bodies are habitats. Just as a forest provides a habitat for birds and squirrels, our bodies provide the local environment in which these beings live. And survival in these environments presents a range of challenges. Like all forms of life, viruses compete with each other for access to resources.

Viruses face constant pressure from our immune systems, which have multiple tactics to block their entrance into the body or disarm and kill them when they manage to get in. They face constant life choices: should they spread, which risks capture by our immune systems, or remain in latency, a form of viral hibernation, which can provide protection but sacrifices offspring.

Transmission from host to host is such a fundamental need for infectious agents that some take it a step further.

The majority of microbes that cause infection in humans are relatively harmless, but some have a striking capacity to make us sick. This can sometimes be expressed in the form of, say, a common cold (caused by a rhinovirus or adenovirus) but can also manifest itself in life-threatening illnesses such as smallpox.

Deadly microbes are a consistent challenge to evolutionary biologists because of their paradoxical habit of eviscerating habitats upon which they depend for their own survival. It’s analogous to a bird destroying the forest in which it and its descendants live. Yet the process of evolution occurs largely at the level of the individual or even the gene.

 Evolution does not proceed with forethought, and there’s nothing to stop a virus from spreading in such a way that leads to a dead end. Such virally induced extinction events have undoubtedly occurred throughout the history of interactions with microbes, no matter the ultimate cost for virus or host.

More central from the perspective of a virus is the impact of disease on transmission. On average, each germ must infect at least one new victim for every old one who either dies or recovers and purges himself of the microbe in order to avoid extinction. This is the rule of basic reproduction. If the average number of new victims per old victim drops to less than one, then the spread of the microbe is doomed. Since microbes generally can’t walk or fly from one host to the next they often strategically alter their host to help in their spread. From the perspective of a bug, a symptom can be an all-important means of enlisting our help in moving itself around. Microbes often make us cough or sneeze, which can permit them to spread through our exhaled breath, suffer from diarrhea, which can spread microbes through local water supplies, or cause open sores to appear on our skin, which can spread through skin-to-skin contact. In these cases it’s obvious why a microbe would trigger these generally unpleasant symptoms. Unpleasant symptoms are one thing, but killer microbes are quite another.

From the perspective of a bug the impact on its host is only measured in its ability to survive and reproduce. And altering our physical bodies is just the beginning. Some microbes also influence our behavior, effectively making us zombies acting in their benefit.

Truly deadly diseases must strike a balance between the likelihood of causing death in its victim once the victim is infected and their efficacy in terms of allowing the victim to spread the disease to others.

The genome sizes of many cellular forms of life can range into the billions—humans, for example, have around three billion base pairs (i.e., bits of genetic information); corn has around two billion. Certain viruses like HIV and the Ebola virus, which use RNA rather than DNA for their genetic information, manage to live with an average of only ten thousand base pairs of genetic information, an incredible level of biological minimalism. How they manage to replicate with such a small amount of genetic information, let alone do something remarkably complicated, like altering the behavior of their hosts, is truly amazing.

No organisms have perfect fidelity. Any time a cell in our body or a bacterium divides to create daughter cells or a virus replicates in a host cell, errors creep in. This means that even in the absence of sexual mixing, offspring are never the same as their parents. Yet viruses have taken mutation to a completely new level.

Viruses have some of the highest mutation rates of any known organisms. Some groups of viruses, such as RNA viruses, have such high error rates that they approach a threshold where any higher level of mutation would make them effectively crash due to the loss of Viruses have some of the highest mutation rates of any known organisms. Some groups of viruses, such as RNA viruses, have such high error rates that they approach a threshold where any higher level of mutation would make them effectively crash due to the loss of essential function from the resulting errors. While many of the mutations harm the new viruses, the high number of offspring that viruses produce increases the chances that some mutants survive and occasionally out perform their parents. This raises the chances that they will successfully evade the immune systems of their host, get the upper hand against a new drug, or gain the capacity to jump to a completely new host species.

Pandemic

A mad rush to respond to pandemics has been the mainstay of global public health for the last one hundred years. Now a small but vocal group of scientists have begun to argue that we must do better than just respond to pandemics by scrambling for vaccines, developing drugs, and modifying behaviors. This traditional approach has proved a failure for human immunodeficiency virus (HIV), which nearly thirty years after its discovery continues to spread, infecting  millions of people.

We still understand surprisingly little about pandemics and the microbes that cause them. We know even less about how to predict or prevent pandemics before they spread from small towns to cities and the rest of the world. Pandemics will increase in frequency in the coming years as the connections between human populations and the animals in our world continue to grow.

Deadliness of H5N1 and the potential to spread like H1N1, a resurgent SARS, a new retrovirus like HIV, or perhaps most frighteningly, a completely novel microbe that blindsides us, microbial threats will grow in the coming years in their ability to plague us, kill people, destroy regional economies, and threaten humanity in ways more severe than the worst imaginable volcanoes, hurricanes, or earthquakes.

First pandemic in history.

In early July 2002 in Franklin County, Tennessee, a thirteen-year-old boy named Jeremy Watkins picked up a sickly bat on his way home from a day of fishing. None of the other family members handled it, and his stepfather wisely made him release the animal soon after Jeremy revealed his find.

Events like this happen all over the world with thousands of wild animals every day, largely without ill consequences. But Jeremy’s encounter with this particular bat would be quite different.

In the CDC report that would document Jeremy’s case, the next events were described with clinical efficiency. On August 21 Jeremy complained of headache and neck pain. Then a day or so later his right arm became numb and he developed a slight fever. Perhaps of greater concern, he also developed diplopia, or double vision, and a constant, queasy confusion. Three days later he was taken to the local hospital’s emergency room but was discharged with the incorrect diagnosis of “muscle strain.” The next day he was back in the emergency room, this time with a fever of 102°F. He had the same symptoms, but now his speech was slurred, he had a stiff neck, and difficulty swallowing. This became the first pandemic in history.

He was also producing copious amounts of saliva. Highly agitated to the point of being combative, Jeremy was sedated and put on life support. His mental status deteriorated rapidly and by the next morning he was completely unresponsive. On August 31 Jeremy was pronounced brain-dead and, following the withdrawal of life support, he died of bat-borne rabies.

the incubation period for rabies is generally three to seven weeks, well within the range of the time between his exposure to the bat and the first symptoms he experienced. Detailed studies of the virus that killed Jeremy revealed evidence of a variety of rabies found in silver-haired and eastern pipistrelle bats common in Tennessee.

If we take a different view, the virus that causes rabies is not only a deadly menace but also a truly amazing feat of nature. This virus, shaped like a bullet, is a meager 180 nanometers long and 75 nanometers across.

While diminutive, the virus accomplishes remarkably sophisticated tasks. In addition to the standard viral work of invading cells, releasing genes, making new viruses, and spreading, it has some unique tricks. From the point of entry, the virus travels preferentially along neural pathways, making its way into the central nervous system. It accumulates selectively in the saliva. The virus particles that infect the central nervous system modify the host’s behavior, increasing aggression, interfering with swallowing, and creating a profound fear of water.

What is a pandemic? Defining them creates some trouble. The word itself comes from the Greek pan, meaning “all,” and demos, meaning “people.” Yet, in reality, it is almost impossible to imagine an infectious agent that infects the entire human population, a high bar to set for a virus. In humans or any hosts, different individuals will have different genetic susceptibility, so at least a few individuals will likely be incapable of sustaining an infection because of some kind of genetic immunity. Also, the simple logistics of spreading to every single individual in any population makes such a feat nearly impossible.

The WHO faced widespread criticism for labeling H1N1 a pandemic in 2009, but that’s exactly what it was. H1N1 went from infecting only a few individuals in early 2009 to infecting people in every region of the world by the end of the same year. If that’s not a pandemic, then I don’t know what is. Whether or not we label a microbe that’s spreading as a pandemic is unrelated to its deadliness.

A virus that didn’t cause any immediate harm would likely be missed.

Of course, “immediate” isn’t the same thing as “never.” If a virus like HIV were to enter into humans today and spread globally, it wouldn’t be detected for years, since major disease would occur sometime after initial infection. HIV causes only a relatively minor set of syndromes immediately, even though it starts to spread right away. AIDS, the major disease of HIV, doesn’t emerge until years later. Since conventional methods for detecting new pandemics rely primarily on seeing symptoms, a virus that spreads silently would likely miss our radar, spreading to devastating levels before an alarm could be triggered.

Missing the next HIV would obviously be a catastrophic public health failure. Yet new viruses, even if likely to be completely harmless, like TTV(transfusion-transmissible virus (A single-stranded DNA virus, found in recipients of blood transfusions, that colonizes in the liver) and GBV (GBV-C: GB virus C, a virus first identified in 1995 that is genetically related to the hepatitis C virus but which does not cause hepatitis in humans. The exact role of GBV C in producing disease in humans remains unclear.

Infection with GB virus C (GBV-C) may be beneficial to HIV-infected patients. There are studies suggesting that these patients enjoy longer survival if they are coinfected with this virus and HIV than if they have HIV alone.

GB virus C (GBV-C) is also called hepatitis G. However, the designation GB virus C (GBV-C) is preferred because the virus is not a cause of hepatitis.), need to be monitored if they are moving quickly through the human population.

Viruses can change. They can mutate. They can recombine with other viruses, mixing genetic material to create something new and deadly. If there’s a new virus in humans and it’s spreading globally, we need to know about it. The dividing line from spreading and benign to spreading and deadly is a potentially narrow one.

For our purposes, we’ll define a pandemic as a new infectious agent that has spread to individuals on all continents.

In Faust, Goethe wrote,

’Tis writ, “In the beginning was the Word.”

I Pause, to wonder what is here inferred.

The Word I cannot set supremely high:

A new translation I will try.

I read, if by the spirit, I am taught,

This sense, “In the beginning was the Thought….”

When it came, they placed their lives in the path of the disease and applied all their knowledge and powers to defeat it. As it overwhelmed them, they concentrated on constructing the body of knowledge necessary to eventually triumph. For the scientific knowledge that ultimately came out of the influenza pandemic pointed directly—and still points—to much that lies in medicine’s future.

The Great influenza

THE GREAT WAR had brought Paul Lewis into the navy in 1918 as a lieutenant commander, but he never seemed quite at ease when in his uniform. It never seemed to fit quite right, or to sit quite right, and he was often flustered and failed to respond properly when sailors saluted him.

Yet he was every bit a warrior, and he hunted death.

When he found it he confronted it, challenged it, tried to pin it in place, so he could then dissect it piece by piece, analyze it, and find a way to confound it. He did so often enough that the risks he took became routine.

Still, death had never appeared to him as it did  in mid-September 1918. Row after row of men confronted him in the hospital ward, many of them bloody and dying in some new and awful way.

He had been called here to solve a mystery that dumbfounded the clinicians. Lewis was a scientist. Although a physician he had never practiced on a patient. Instead, a member of the very first generation of American medical scientists, he had spent his life in the laboratory. He had already built an extraordinary career, an international reputation, and he was still young enough to be seen as just coming into his prime.

A decade earlier, working with his mentor at the Rockefeller Institute in New York City, he had proved that a virus caused polio, a discovery still considered a landmark achievement in the history of virology. He had then developed a vaccine that protected monkeys from polio with nearly 100 percent effectiveness.

The clinicians now looked to him to explain the violent symptoms these sailors presented. The blood that covered so many of them did not come from wounds, at least not from steel or explosives that had torn away limbs. Most of the blood had come from nosebleeds. A few sailors had coughed the blood up. Others had bled from their ears. Some coughed so hard that autopsies would later show they had torn apart abdominal muscles and rib cartilage. And many of the men writhed in agony or delirium; nearly all those able to communicate complained of headache, as if someone were hammering a wedge into their skulls just behind the eyes, and body aches so intense they felt like bones breaking. A few were vomiting. Finally the skin of some of the sailors had turned unusual colors; some showed just a tinge of blue around their lips or fingertips, but a few looked so dark one could not tell easily if they were Caucasian or Negro. They looked almost black.

At autopsy their lungs had resembled those of men who had died from poison gas or pneumonic plague, a more virulent form of bubonic plague.

At autopsy their lungs had resembled those of men who had died from poison gas or pneumonic plague, a more virulent form of bubonic plague.

Philadelphia navy authorities had taken Rosenau’s warnings seriously, especially since a detachment of sailors had just arrived from Boston, and they had made preparations to isolate any ill sailors should an outbreak occur. They had been confident that isolation would control it.

The hospital ran out of empty beds, and hospital staff began falling ill. The navy then began sending hundreds more sick sailors to a civilian hospital. And sailors and civilian workers were moving constantly between the city and navy facilities, as they had in Boston. Meanwhile, personnel from Boston, and now Philadelphia, had been and were being sent throughout the country as well.

Lewis had visited the first patients, taken blood, urine, and sputum samples, done nasal washings, and swabbed their throats. Then he had come back again to repeat the process of collecting samples and to study the symptoms for any further clues. In his laboratory he and everyone under him poured their energies into growing and identifying whatever pathogen was making the men sick. He needed to find the pathogen. He needed to find the cause of the disease. And even more he needed to make a curative serum or a preventive vaccine.

Lewis loved the laboratory more than he loved anyone or anything. His work space was crammed; it looked like a thicket of icicles—test tubes in racks, stacked petri dishes, pipettes—but it warmed him, gave him as much and perhaps more comfort than did his home and family. But he did not love working like this. The pressure to find an answer did not bother him; much of his polio research had been conducted in the midst of an epidemic so extreme that New York City had required people to obtain passes to travel. What did bother him was the need to abandon good science. To succeed in preparing either a vaccine or serum, he would have to make a series of guesses based on at best inconclusive results, and each guess would have to be right.

He had already made one guess. If he did not yet know precisely what caused the disease, nor how or whether he could prevent it or cure it, he believed he knew what the disease was.

He believed it was influenza, although an influenza unlike any known before.

But the men in the wards now not only puzzled medical men . They had to have chilled him with fear also, fear both for himself and for what this disease could do. For whatever was attacking these sailors was not only spreading, it was spreading explosively.

In 1918 an influenza virus emerged—probably in the United States—that would spread around the world, and one of its earliest appearances in lethal form came in Philadelphia. Before that worldwide pandemic faded away in 1920, it would kill more people than any other outbreak of disease in human history. Plague in the 1300s killed a far larger proportion of the population—more than one-quarter of Europe—but in raw numbers influenza killed more than plague then, more than AIDS today.

The lowest estimate of the pandemic’s worldwide death toll is twenty-one million, in a world with a population less than one-third today’s. That estimate comes from a contemporary study of the disease and newspapers have often cited it since, but it is almost certainly wrong. Epidemiologists today estimate that influenza likely caused at least fifty million deaths worldwide, and possibly as many as one hundred million. 

Normally influenza chiefly kills the elderly and infants, but in the 1918 pandemic roughly half of those who died were young men and women in the prime of their life, in their twenties and thirties. Harvey Cushing, then a brilliant young surgeon who would go on to great fame—and who himself fell desperately ill with influenza and never fully recovered from what was likely a complication—would call these victims “doubly dead in that they died so young.”

Died with extraordinary ferocity and speed. Although the influenza pandemic stretched over two years, perhaps two-thirds of the deaths occurred in a period of twenty-four weeks, and more than half of those deaths occurred in even less time, from mid-September to early December 1918. Influenza killed more people in a year than the Black Death of the Middle Ages killed in a century; it killed more people in twenty-four weeks than AIDS has killed in twenty-four years.

The influenza pandemic resembled both of those scourges in other ways also. Like AIDS, it killed those with the most to live.

Yet the story of the 1918 influenza virus is not simply one of havoc, death, and desolation, of a society fighting a war against nature superimposed on a war against another human society.

It is also a story of science, of discovery, of how one thinks, and of how one changes the way one thinks, of how amidst near-utter chaos a few men sought the coolness of contemplation, the utter calm that precedes not philosophizing but grim, determined action.

For the influenza pandemic that erupted in 1918 was the first great collision between nature and modern science. It was the first great collision between a natural force and a society that included individuals who refused either to submit to that force or to simply call upon divine intervention to save themselves from it, individuals who instead were determined to confront this force directly, with a developing technology and with their minds.

All at once, it seems, new viruses and virus-related diseases have  threatened the health of humans and many animal species. How  did this situation arise? Could it be that scientific studies and the  emergence of new pathogens are not totally unrelated events?

Despite its social and scientific importance, the origin of HIV has  been clouded in mystery. Based on the mass of circumstantial  and scientific evidence presented herein, the theory that  "emerging viruses" like HIV and Ebola spontaneously evolved  and naturally jumped species from monkey to man must be  seriously questioned.

There is an old saying in medicine, that diagnosis is required  before treatment. The facts presented here, easily verified, may  help diagnose the man-made origin of the world's most feared  and deadly viruses. It is hoped this work will, therefore, help  redirect AIDS science in search of a cure, free AIDS victims  from the guilt and stigma attached to the disease, as well as  prevent such "emerging viruses' ' from reemerging.  I offer this investigation into the origin of AIDS and Ebola for  critical review in the hope that it may also contribute to greater  honesty in science, to political, military, and intelligence  community reforms that are truly peace loving, and to self and  social reflection as a preventative against inhumanity.

Scientific research and lax government oversight may  have contributed to the present and coming plagues.  Open debate on this issue has been soundly discouraged. 

 Opponents to open dialogue on the apparent relationship between  early viral research and the latest germ discoveries argue that  little good, and considerable harm, would come from a full  disclosure of the facts. Exposing the truth, many believed, would likely: 

I) tarnish the reputations of certain scientists,

 2) make it  more difficult to maintain science funding,

 3) promote  anti government sentiment, and 

4) likely to leave many issues  unresolved. 

Others argued that it was simply too late to undo past  mistakes. The fact that a better understanding of the new viruses'  origins could lead to new treatment approaches, and, more  importantly, to ways of preventing future outbreaks, was  disregarded. 

 In considering the recent genesis of HIV and the Ebola viruses, has explored three areas of great general and  scientific interest:

 1) the history of intensive research into the  viral causes of cancer wherein readers can become familiar with  the many, now questionable, virus transmission experiments,

 2)  the CIA and Department of Defense efforts to develop and  defend against biological weapons of germ warfare. 

Well researched little known facts that, though highly disturbing, are  an important piece of history that may also bear heavily on the  emergence of new viruses, and 

3) vaccine production. 

In 1798, Edward Jenner, an English physician, advanced the use  of cowpox (vaccinia) virus for immunizing humans against  smallpox. He recognized that pathogens can behave differently  while infecting different species. Indeed, he theorized that the  vaccinia infection, which caused mild problems for cows, caused  more severe ailments in horses. Only after adapting to cows, did  vaccinia acquire limited infectivity for humans. The open sores  that humans developed were far less severe than those induced by  smallpox (variola) virus and essentially remained localized to the  site of inoculation. Moreover, contact with vaccinia virus caused  individuals to become virtually immune to the widespread  disease caused by the small-pox virus. The success of vaccination  is reflected in today's total elimination of smallpox as a disease.  Jenner's vaccination approach was followed in the twentieth  century by Pasteur's use of rabies virus grown in rabbit's brain,  and by Theiler's finding that he could reduce the effect of yellow  fever virus by growing it in chicken embryos.

These successes set the precedent for other scientists to attempt  to reduce the pathogenicity of other human and animal viruses by  inoculating them into foreign species. Although we now look  back with some disdain at the crudeness of early immunization  experiments - such as the 1938 injections of poliovirus, grown in  mouse brains, into humans, most people, including scientists, are  unaware that we still use primary monkey kidney cells to produce  live poliovirus vaccines. Likewise, dog and duck kidney cells  were used to make licensed rubella vaccines. Experimental  vaccines, grown in animal tissues and intended for human use,  were commonly tested in African monkeys, and it is likely that  many of these monkeys were released back into the wild. This  practice may have led to the emergence of primate diseases, some  of which could have been transmitted back to humans.  Large numbers of rural Africans were also chosen as test  recipients of experimental human vaccines.  In veterinary medicine, live viral vaccines have been widely used  in domestic pets and in animals destined to become part of the  food-chain. Undoubtedly, many cross-species transfer of viruses  have occurred in the process.

Polio  vaccines may also have contained numerous other monkey  viruses, some of which may have provided some building blocks  for the emergence of HIV-l and human AIDS.  The finding of SV40 in rhesus monkey kidney cells, during the  early 1960s, led to a rapid switch to Mrican green monkeys for  polio vaccine production. Kidney cells from African green  monkeys, still being used to produce live polio vaccines today,  may have been infected with monkey viruses that were not easily  detectable. The monkeys used before 1980, for example, were  likely to have been infected with simian immunodeficiency virus  (SIV)-a virus genetically related to HIV-l. 

The origin of this virus  and whether it contaminated any experimental vaccines are issues  that need addressing.

  What makes vaccines so troublesome is that their production and  administration allows viral contamination to breach the two  natural barriers that often restrict cross-species infections:  First is the skin. 

Direct inoculation of vaccines breaches this natural barrier and has been shown to produce increased  infections in animals and humans.

Second is the unique and natural viral surface characteristics that  reduce the chance that viruses might jump species. The mixing of  vaccine viruses with others found in the cells and tissues used to  develop the vaccine can potentially lead to the development of  new recombinant mutants that are more adaptive and have wider  host range than either of the original viruses. This can especially  happen when a live viral vaccine produced in cells from one  species is then given to another species.  Also of concern is the transmission of new genetic information  along with the vaccine virus. For instance, early adenoviral  vaccines, produced in rhesus monkeys' kidney cells, developed to  protect people against respiratory infections, incorporated parts  of the SV40 virus that remained as a vaccine contaminant even  after production of the vaccine virus was switched to human  cells. Numerous other vaccines, especially those that were used  in early field trials in Africa, should be analyzed for those genetic  components which characterize today's monkey and human  pathogens.

It is against this background of possible risks of past viral vaccine  studies, uncertain biological recombinants, bureaucratic  censorship, a rising tide of medical consumerism in the  information age, and an urgent need for legislative FDA reform,  that Dr. Horowitz's work contributes.

 At minimum, exposes many important facts  which, unfortunately, few people realize and all would be better  off knowing. At best, it is important and raises far greater hope  that by knowing their origin, cures for the many complex  emerging viruses, including AIDS, may be forthcoming.

From :  Emerging Viruses

The World Health Organization (WHO) theory  festered in my  mind like a disease. That the AIDS virus was cultured as a  biological weapon and then deliberately deployed was  unfathomable. How could WHO scientists and others in the  United States Public Health Service (USPHS) consciously or  even unwittingly create such a hideous germ? More  inconceivable was the alleged targeting of American  homosexuals and black Africans for genocide. The entire subject  was beyond my wildest nightmares.  Frightened by the ramifications of such alleged atrocities, I spent  months living in denial. As a behavioral scientist, I was no  stranger to the subject of man's inhumanity toward man. I just  feared what further research might reveal.  Eventually, curiosity wore down my defenses, and I attempted,  on several occasions, to contact Dr. Robert Strecker for an  explanation. For months, then, the telephone number I had for  him rang continuously unanswered. Secretly, I was thankful. The  secondary sources of information I had about 'The Strecker  Memorandum' were adequate for my needs, I rationalized.  The few documents I had on the WHO theory of AIDS came  from a wholistic physician I met at a National Wellness  Association conference. For years, the doctor documented, the  word on the street in the gay community and among the black  intelligentsia was that HIV was created as a bioweapon - a manmade virus bearing stark similarities to the bovine lymphotrophic  virus (BLV :Bovine leukemia virus (BLV) and human T-lymphotrophic virus type-1 (HTLV-1) are related retroviruses associated with persistent and lifelong infections and a low incidence of lymphomas within their hosts. Both viruses can be spread through contact with bodily fluids containing infected cells, most often from mother to offspring through breast milk. Each of these complex retroviruses contains typical gag, pol, and env genes but also unique, nonstructural proteins encoded from the pX region. These nonstructural genes encode the Tax and Rex regulatory proteins, as well as novel proteins essential for viral spread in vivo. Improvements in the molecular tools to test these viral determinants in cellular and animal models have provided new insights into the pathogenesis of each virus. Comparisons of BLV and HTLV-1 provide insights into mechanisms of spread and tumor formation, as well as potential approaches to therapeutic intervention against the infections.) cultured in cows. 

Although American authorities  quickly moved to dispel the assertion, claiming African monkeys  were the source of the scourge, Dr. Strecker insisted the germ  came from cow and sheep sources.  Research showed a similarity between HIV and BLV. One report  appeared in 'Nature' in 1987. Strecker heralded this and  argued it was virologically absurd to believe HIV came from the  monkey. Especially "since there are no genetic markers in the  AIDS virus typical of the primate, and the AIDS virus cannot  thrive in the monkey." Still, the majority subscribed to the  African green monkey theory.

According to Strecker, whose work was reviewed by medical  physician Jonathan Collin in a 1988 issue of 'Townsend Letter for

Doctors,' the AIDS virus:   

 ". . . can and apparently does thrive in the cow, having essentially  identical characteristics with the bovine virus and this, further,  gives a hint of the role vaccinations have played in either  accidentally or purposefully inducing the AIDS epidemic."   Collin reported that Strecker's research made sense, particularly  considering the virology and evolution of the AIDS epidemic.  Strecker's first point was that AIDS was nonexistent in Africa  prior to 1975, and had it been the result of monkey bites  occurring in the 1940s, as some alleged, the epidemic should  have occurred in the 1960s and not late 1970s owing to the  twenty-year timetable for case incidence doubling. 

Strecker obtained documents through the Freedom  of Information Act (FOIA) that showed that the United States  Department of Defense (DaD) secured funding from Congress in  1969 to perform studies on immune-system-destroying agents for  germ warfare. Strecker alleged that soon thereafter, the WHO,  funded by the DOD, began experimenting with a lymphotrophic virus (The human T-lymphotropic virus, human T-cell lymphotropic virus, or human T-cell leukemia-lymphoma virus (HTLV) family of viruses are a group of human retroviruses that are known to cause a type of cancer called adult T-cell leukemia/lymphoma and a demyelinating disease called HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). The HTLVs belong to a larger group of primate T-lymphotropic viruses (PTLVs). Members of this family that infect humans are called HTLVs, and the ones that infect Old World monkeys are called Simian T-lymphotropic viruses (STLVs). To date, four types of HTLVs (HTLV-1, HTLV-2, HTLV-3, and HTLV-4) and four types of STLVs (STLV-1, STLV-2, STLV-3, and STLV-5) have been identified. HTLV types HTLV-1 and HTLV-2 viruses are the first retroviruses discovered. Both belong to the oncovirus subfamily of retroviruses and can transform human lymphocytes so that they are self-sustaining in vitro.[1] The HTLVs are believed to originate from interspecies transmission of STLVs. The HTLV-1 genome is diploid, composed of two copies of a single-stranded RNA virus whose genome is copied into a double-stranded DNA form that integrates into the host cell genome, at which point the virus is referred to as a provirus. A closely related virus is bovine leukemia virus BLV. The original name for HIV, the virus that causes AIDS, was HTLV-3.) that was produced in cows, but could also infect humans.  

The WHO, Strecker noted, also launched a major African  campaign against smallpox in 1977, which involved the urban  population, not the rural Pygmies. Had the "green monkey" been  responsible for AIDS, Strecker professed, the Pygmies of rural  Africa would have had a higher incidence of AIDS than the  country's urban populations. The opposite is  true.   Strecker reportedly examined WHO research that revealed their  scientists, in the early 1970s, had studied viruses that were  capable of altering the immunologic response capacity of Tlymphocytes. He noted that such viruses were found in 1970, but  only in some animals including sheep and cows, and that the  latter species is used to produce the smallpox vaccine.  Literature provided by The Strecker Groups urged readers to:    

"PLEASE WAKE UP!   

 In 1969 . . . [the] United States Defense Department requested  and got $10 million to make the AIDS virus in labs as a  political/ethnic weapon to be used mainly against Blacks. The  feasibility program and labs were to have been completed by  1974-1975; the virus between 1974-1979. The World Health  Organization started to inject AIDS-laced smallpox vaccine into  over 100 million Africans (population reduction) in 1977. And  over 2000 young white male homosexuals (Trojan horse) in 1978  with the hepatitis B vaccine through the Centers for Disease  Control/New York Blood Center. . . ."

There are two things about the biological agent field I would like  to mention. One is the possibility of technological surprise.  Molecular biology is a field that is advancing very rapidly and  eminent biologists believe that within a period of 5 to 10 years it  would be possible to produce a synthetic biological agent, an  agent that does not naturally exist and for which no natural  immunity could have been acquired.

Hundreds of strains of rhinoviruses have been isolated and  shown to be antigenically distinct from at least some other  strains. They have been reported in the scientific literature under  a confusing variety of designations, and it was accordingly  decided at a meeting of the Directors of the WHO Virus  Reference Centers to undertake collaborative study in which sera  and strains were distributed to a number of laboratories so that  cross neutralization tests could be performed of all well characterized and apparently new strains. This work was  supported by the US Vaccine Development Board and coordinated by the two WHO International Reference  Centres. . . ."    "Work on these viruses," Tyrrell continued, demanded "a supply  of cells'' that were "sensitive to such organisms." It required  considerable work to find such cells. Often cell lines would  "change their sensitivity after prolonged cultivation." The  Reference Centres, thus, maintained stocks of cells, "stored in  liquid nitrogen," which they distributed to labs conducting viral  research throughout the world.    Some viruses that failed to grow in the usual tissue cultures,  Tyrrell revealed, "were propagated in cultures of the human  trachea and nose," that is, "in the organs and tissues in which  they multiply in nature." These viruses, some "new rhinoviruses,"  and other new types "never before detected in man were  "disseminated through the WHO network of Virus Reference

"I'm not sure," I replied, "but most likely. There was obviously  lots of money to be made with vaccines, and only a few  companies made them."  "Which ones?"  "Well Merck, Sharp and Dohme (MSD) is one of the largest, and  they did fund the hepatitis B vaccine research Strecker alleged  spread HIV to homosexuals in America."  Another report four months later showed Israeli scientists were  supported by the WHO to study the genetic determinants of the  human immune response.

 A few others stated that the WHO was funding several programs  designed to evaluate the specific disease vulnerabilities of  minority groups - from American Indians to African natives - through the collection and analysis of "gene pools" and  "blood supplies."   "That's just what the Nazis did," Jackie recalled.  "Here are a couple more articles noting the WHO and the U.S.  Vaccine Development Board also funded 'large-scale human  trials' of newly developed vaccines made from both bacterial and  viruses."   "Let me see."  I passed the reports over to my co-investigator.

The Atlanta lab was run by the CDC's predecessor - the National  Communicable Disease Center (NCDC). The Bethesda lab was  run by the NIH. The latter was cited in the WHO Chronicle as one  of the initial two International [virus] Reference Centers. Yet, it  was reported to be inadequately equipped to handle dangerous smallpox viruses. These were allegedly handled in Atlanta.  "If that's the case, it's not likely they would have handled deadly  viruses like HIV either," 

Jackie reasoned.  "Not necessarily," I responded. "The smallpox virus and the  DOD requisition may have posed different risks."  Shortly after our conversation, an article by Charles Siebert in  'The New York Times Magazine' clarified the biological safety  level (BSL) risk rating system used by the CDC and the NIH:    "In the hierarchy of precaution taken against biological threats at  the CDC, BSL I and 2 are the lowest level of safety. Work is  done there only with non - or moderate-risk organisms - viruses  that cause colds, for example, or bacteria that cause diarrhea. At  BSL 3, known as "the hot zone" or the "blue suit lab," workers  visit with highly transmissible viruses or with those viruses or  bacteria for which there is no known cure. There are only two  BSL 4 labs in the country, one at the United States Army Medical.

Among the tens of thousands of viral strains cultured, developed,  and transported for study by WHO reference centers, we learned  that two received special attention and an inordinate share of  research dollars: monkey viruses, including the simian pox virus,  and the "slow" viruses, particularly visna and scrapie.  We read these reports carefully since Strecker noted the AIDS  virus bears the greatest likeness to the human-bovine (cow).

Lymphotrophic (lymph-cell-targeting and cancer-causing) virus  combined with sheep visna virus.   Monkeypox was of great interest to researchers, the 'WHO  Chronicle' said, for two reasons. 

First, the monkeypox virus was  found closely related to the variola-vaccinia virus group, which  causes and immunizes against human smallpox. 

Second, the  monkey is man's closest relative in the animal kingdom, and  experimental results using monkeys were expected to provide the  best indication of what might occur in humans exposed to the  same elements.  Alternatively, "slow" viruses were of the greatest interest to  WHO, CDC, NIB, and NCI scientists between 1968 and 1974.  The reasons for this were not as obvious. 

The 'WHO Chronicle'  reported:    "Recent interest in the "slow" viruses, in particular those causing  chronic degenerative disease of the nervous system-the CHINA  (chronic infectious neuropathic agents) viruses-has come from  painstaking work with visna and scrapie, degenerative diseases of  the central nervous system of sheep, and kuru, a degenerative  disease of the central nervous system of man restricted to the  Fore people of New Guinea and their immediate neighbours."    

 "Why so much interest in two sheep viruses that cause nerve  disorders and don't infect humans?" Jackie asked.

  "I'm not sure."  "And what about kuru? Who are the 'Fore people of New  Guinea'?  What makes them so important that viral centers around the  world took up their cause?"  "Well, let's look it up." I walked over to our library and pulled  out a copy of Steadman's Medical Dictionary.  "Kuru, it says is'':    "A highly localized, fatal disease found in New Guinea,  resembling paralysis agitans [a nervous disorder with frequent  bouts of shaking]; found among certain cannibalistic people who  ingest raw brain of recently deceased victims of the disease. Also  called a laughing sickness."  "When in history has helping cannibals been a world priority?" I  wondered.  "Never," Jackie responded. "The notion seems utterly  harebrained."  "Oh. That was awful."  "Sorry, I couldn't help myself."

"HIV is a single-stranded RNA 'slow' virus," I explained. "And  gene cutting and splicing techniques were well developed at that  time." "Could they have cut double-stranded RNA to make single-stranded RNA?"  "I'm not sure, but what I don't understand is, here, the 'WHO  Chronicle' stated the primary objective of their viral research  program was to acquire a thorough knowledge of the virus  diseases so that prophylactic and other public health measures  can be introduced as soon as possible.

"A new infective microorganism which could differ in certain  important aspects from any known disease-causing organisms.  Most important of these is that it might be refractory to the immunological and therapeutic processes upon which we depend  to maintain our relative freedom from infectious disease."    "It is a highly controversial issue and there are many who believe  such research should not be undertaken lest it lead to yet another  method of massive killing of large populations. . . ."    The following week we learned that despite heavy opposition by  the public and the House of Representatives, the United States  Congress gave the Army $23.2 million for biological warfare  research. About half of that, at least $10 million of taxpayer  money, went directly toward funding the manufacture of  immunosuppressive agents allegedly for defense.  "In essence, this one 1970 DOD biological weapons  appropriation cost more than half of all the money the WHO  spent in Africa that year for all of their health care and  vaccination programs."

 

However, in a somewhat less direct fashion, WHO has exerted a  powerful influence on the quality control of biological substances  since its very inception in 1948. The work of setting up and  distributing international biological standards was not started by  

WHO but was taken over, already in an advanced stage of  development, from the Health Committee of the League of  Nations. Indeed the first few international standards for  biological substances were established by a national body, the  Statens Seruminstitut, Copenhagen, a few years before the  creation of the Health Committee.  The very first such standard - the International Standard for  Diphtheria Antitoxin, which consists of a dried hyperimmune  horse serum - was established in 1922 and it is still in use today.  It says much for the forethought and wise choice of the early  authorities, as well as for the stability of at least some biological  products, that a single preparation has served world requirements  for a period of 46 years. The supply of this particular standard is  expected to last for at least another 46 years.  From this small start in 1922, and up until 1948, when WHO was  established, the number of international standards distributed by  the League of Nations grew to 32, in the categories enumerated. Also, in recent  years, 96 inter-  national biological reference reagents have been established by  WHO. 

Generally, these are intended as reference materials for substances used in the diagnosis of disease and in the  identification of micro-organisms. Many leptospiral typing  antisera are included among these reagents, and a recently  established set of viral typing antisera is being rapidly expanded.  Classification of the current international  preparations, with comparative figures for 1948.  In general, the main purpose served by these international  standards, reference preparations, and reference reagents is to  provide a means of ensuring world-wide uniformity in expressing  the potency of preparations used in the prophylaxis, therapy, or  diagnosis of human and animal disease.

 Most of the substances  for which these international standards, etc. have been  established could not, at least at the time of their establishment,  be characterized fully by chemical and physical means. The  activity of an ill-characterized substance may be measured by  biological assay, and the results may be best  expressed as a ratio of its activity to the activity of a closely  similar physical specimen, designated the international standard.  In many ways, the definition of an international…

"In a word, the intentional release of an infectious particle, be it a  virus or bacterium, from the confines of the laboratory or of  medical practice must be condemned as an irresponsible threat  against the whole human community. . . ."    "We have learned in recent years that viruses undergo constant  evolution in their own natural history, not only by mutations  within a given strain, but also by the natural cross-hybridization  of viruses that superficially appear to be only remotely related to  one another. Furthermore, many of us carry viruses in our body  cells of which we are unaware for years and which may be  harmless - though they may eventually cause the formation of a  tumor, or of brain degeneration, or of other diseases. At least in  the laboratory, we can show that such latent viruses can still  cross-breed with other viruses to give rise to new forms. . . ." 

  "We are all familiar with the process of mutual escalation in  which the defensive efforts of one side inevitably contribute to  further technical development on the other, and vice versa. . . .  And the potential undoubtedly exists for the design and  development of infective agents against which no credible  defense is possible, through the genetic and chemical  manipulation of these agents."    'Nature,' 'Science,' and 'Lancet' published dozens of articles  expressing grave concerns over the fate of humanity should  biological weapons research continue. One such article entitled  "The Biological Bomb," written by an anonymous author,  discussed the ethical implications of biological weapons research  - an industry that lay "at the heart of the cellular nucleus, ticking  us to destruction." Dr. V. W. Sidel, a Boston physician, declared that not only  should medical personnel refuse to participate in such activities,  but physicians "must actively protest against the development,  production, and use of biological weapons." Failure to do so, he  argued, represented an insult to the medical profession,  complicity, and one of the greatest dangers to society. 

Another English notable, Lord Ritchie-Calder, summoned  support for an international biological weapons accord and haled  one group of scientists who were devoted to preventing diseases  over another who was busy "devising man-made epidemics." Likewise, another anonymous author published in 'Lancet':    "The whole field [of biological warfare] bristles with difficulties.  Organisms for biological warfare can be produced quickly,  cheaply, and easily; many are required in ordinary and perfectly  legitimate ways for production of vaccines; clandestine research  could easily be conducted; storage is scarcely necessary, for  chemical plants and even breweries could be quickly switched to  producing harmful microorganisms in enormous quantities; and  delivery systems are multiple. . . ." 

   "The Government could give a sound basis to its Geneva  proposal by declaring all future work carried out at Porton  declassified. . . . 

Inside Porton Down, the UK's top secret laboratory, scientists carry out research into chemical weapons and deadly diseases. BBC security correspondent Frank Gardner was given rare access to the highly secretive facility.

Pulling on thick, protective gloves several times a day comes with unique problems, says Rory, one of the youngest scientists currently working at Porton Down.

"The one thing which I've found is definitely moisturiser comes in handy," he says.

"My desk is covered in different types of it."

Ebola, plague, anthrax

Rory works at the Ministry of Defence's Defence Science and Technology Laboratory (DSTL), better known as Porton Down.

Based five miles (8km) outside Salisbury, in Wiltshire, it is highly secretive, under armed guard and is very hard to get into.

And for good reason.

The laboratories are where some of the country's top scientists carry out research into the world's most dangerous pathogens - diseases that can kill us.

Ebola, plague and anthrax are among the life-threatening diseases under study at this secluded base.

It's also where scientists analysed samples confirming that a Novichok nerve agent had been used to poison former Russian spy Sergei Skripal and his daughter.

https://www.bbc.com/news/uk-48540653

This would carry special conviction if. . . it  were linked to participation with WHO. . . . In 1963 Prof. Roger  M. Herriott!l of the Johns Hopkins School of Public Health,  suggested that the United States should offer to place its  biological laboratories under WHO if Russia and other countries  agreed to do the same. The risks to national security in this  procedure are a good deal less than might be thought, for despite  all the secrecy, it seems to be difficult for any country to steal a  march on another in this sphere where the essential basic  knowledge is so readily obtainable."    "These large and frankly political questions may hardly seem of  pressing concern to the medical profession. But biological  warfare implies a misuse of medical science for which doctors  cannot evade responsibility. Medical knowledge and medical  participation are inherent in most of its projects, and the  profession's silence on this issue is liable to be interpreted as  consent. The secrecy demanded is also contrary to the principles  of medical ethics and is totally rejected in every other medical  activity. If the fetters of secrecy were discarded and an  international orientation adopted, more immediate and  constructive thought could be given to feeding the world's 1000  million under-nourished citizens." 

WHO consultants additionally predicted grave psychosocial  consequences of such an escape, including mass hysteria:   

 "They thus present a real danger that is conducive to both anxiety  and fear. Anxiety in particular may result from the fact that many  chemical and all biological agents are undetectable by the senses,  so that there are no warning signs to enable people to defend  themselves. In addition, with biological agents, there is the latent  period between infection and illness and the fact that the extent to  which an infection may spread through a community is unpredictable. As a result, an exposed person cannot be sure  whether he has been infected or know how ill he will be or when  the danger has passed. A further confusing factor is that many of  the symptoms of illness are also symptoms of emotional stress."    That sounded remarkably similar to the "fear of AIDS epidemic"  I had frequently written and talked about. In the event of an attack, the researchers added:    "Panic. . . may be so great that. . . those who have not been  affected will view those who have as potential agents of disease.  The response to a chemical or biological attack may require  precautionary or other measures on such a scale that  extraordinary means of social control will have to be introduced  and these may remain in force long after the need for them has  passed. Thus, an attack may lead to social changes out of all  proportion to the actual damage done."    Isn't that interesting, I thought. They even predicted social  changes like the need to legislate AIDS as a disability rather than  a disease, and requiring infection control measures that have yet  to prove their value in saving costs or lives.  WHO consultants further predicted that the masses would try to  avoid anything that would bring them in contact with deadly  germs. Much of this avoidance was expected to be  disproportionate to the actual risk.  In my role as a health professional AIDS educator, I recalled  several similar experiences. One had occurred a few weeks  earlier following a television interview in Rockford, Illinois. A  viewer called me at the station to express her concern about  leaving her house. The last time she went shopping, she said a  storekeeper handed her a box of laundry detergent. She noticed a  few cuts on his hands and refused to touch him or the box. She  just panicked, left the store, and hadn't gone shopping since.  "Even though casual contact can't transmit HIV," I said to the  station receptionist, "people are still afraid-especially of shaking  hands with AIDS patients or HIV carriers." Exactly what was  predicted, I reflected.  Besides this, the consultants even envisioned extensive health  and medical emergencies as a consequence of a biological attack,  "including mass illnesses, deaths, and epidemics." They expected  that "WHO might be called upon to furnish technical assistance  in dealing with allegations that chemical or biological weapons  had been used. . . and in achieving disarmament."  The authors concluded:    "As long as research on the military use of chemical and  biological agents is continued. . . new agents of even greater  destructive power [may be discovered]. . . . It is clear, therefore,  that the best interests of all Member States, to say nothing of mankind in general, require that the development and use of  chemical and biological agents as weapons of war be outlawed in  all circumstances. The nations of the world must renounce the  use of such weapons, in accordance with the resolutions on  chemical and biological warfare adopted by the United Nations  General Assembly and the World Health Assembly."

Sadly, I realized, their notice fell before blind eyes. Army  medical scientists allegedly wanted vaccines and diagnostic  methods developed quickly in the event of a viral attack. Between 1967 and 1968, the Johnson administration languished  amid cries for America's withdrawal from Vietnam. Richard  Nixon was then propelled to the White House and soon  thereafter, toward détente. Superficially, under Nixon, the world  seemed safer. But in the viral research laboratories of the NIH,  the "cold war" raged.  During this time, the NCI, under NIH administrative direction,  provided the CDC with prototype "reagents"-viruses, vaccines,  antibodies, and cell lines-as the American and international viral  research program advanced. he WHO's Scientific  Group on Viruses and Cancer met in Geneva that year to plan a  common research agenda. The Group, comprised of international  representatives, including three from the United States and one  from Russia, cited the need to study viruses since cancer cells  maintained altered genetic material. Consequently, they  recommended attempts be made "to determine the structural  alterations in cellular nucleic acids," that is, the basic chemical  building blocks of all life. They desired to search for all parts of the virus genome, the genetic makeup or reproductive blueprint  of the viruses, their chemical reaction triggers, or enzymes, or  other "virus-associated intracellular substances." They ordered  study of the "specific changes in the metabolism" of virus  infected cells, and wrote:    "Any genetic structure peculiar to viruses suspected of causing  cancer should be identified and mapped out. Immunological  methods might prove of value, since virus-transformed cells carry  antigenic [that is, foreign chemical] markers. . . . A rust step in  such research would be to induce transformation [cancers] in  various experimental animals with viruses that commonly infect  man. . . ."   "The Group also suggested that, although there is no reason at  present to suspect transmission of animal cancer viruses to man,  any possible relationship that might exist between bovine [cow]  lymphosarcoma [cancer of the lymphatic cells and tissues] or  other mammalian leukemias and human leukemia should be  explored, both by epidemiological studies and by laboratory  research on suspected etiological agents."   "That's exactly what Strecker alleged brought on the AIDS  epidemic," I said. Could this research have really created HIV  and AIDS-related diseases like lymphomas and sarcomas?

Covid 19

In 2015, the Wuhan Institute of Virology (WIV) was upgraded to the National Biosafety Laboratory (Level 4), the first of its kind in China, at a cost of 300 million Yuan ($44 million). The lab was involved in the research of coronaviruses (CoVs) and the causative agents of the severe acute respiratory syndrome (SARS) outbreak in 2003. In 2015, Li et al. published reports about the species of bats acting as natural reservoirs for SARS-like CoVs (SL-CoVs), and pointed out the genetic diversity of the viruses in bats, highlighting the possibility of them infecting the humans. The transmission from palm civets to humans occurred when the civets came into human contact in the live animal markets.As the pools of CoVs in bats were limited, the likelihood of a future emergence of this viral outbreak was never anticipated.

However, when it was proven that a chimeric virus containing the SHC014 spike in a SARS-CoV backbone causes robust infections in both human airway cultures and mice,a warning was issued that the starting materials required for SARS-like emergent strains were already circulating in animal reservoirs. A research team in China that spent 5 years in the Shitou caves of Yunnan sampling from the bats issued a similar warning and raised alerts for a potential disease outbreak if adequate precautions were not taken. By December 2019, the first cluster of cases of infection with a novel CoV was reported in China.

Naturally, the origins of the epidemic were investigated. The WIV published reports stating that the new strain of CoV had bats as the “probable” source.All the studies of Shi Zheng Li, the lead virologist from the institute, on bat-related CoVs were centered in the southern, subtropical areas of Yunnan. However, the outbreak occurred in Wuhan, which is almost 900 km from Yunnan. Samples from the infected patients were compared with those from the bats, but none of them matched. If not from bats, where did this novel strain of CoV come from? The Government of China conducted an investigation and reported a wildlife market, 10 miles away from the virology institute, as the epicenter. Though the Chinese government discredited the possibility of a lab origin based on the genetic studies, the distance of the epicenter from the bat caves raises questions.

The theory of lab origin gains credibility from seemingly unrelated, but nevertheless solid and tangible facts. The institute called for research job openings on November 18, 2019, and December 24, 2019.[8] These urgent advertisements tell us about the kind of research taking place in the labs and also underline the fact that the Chinese knew about the possibilities of novel strains even before the outbreaks that warranted research. The lab then generated a chimeric virus from the SARS-CoV using the reverse genetics approach and reported the potential for human emergence.The leak could have happened from this lab.

On February 6, 2020, scientists from the South China University pointed out that the intermediate host, the horseshoe bat, was not available in the wet market and did not live in the Wuhan area.[9] The only place the bats existed in the locality was the research facility, which is just about a 100 yards from the Wuhan wet market. The horseshoe bats are found only in the Yunnan province. However, they are neither consumed as food in the city, nor are they ever traded in the markets. The paper also states that in the Wuhan Center for Disease Control and Prevention located 280 m from the market, the extraction and sequencing of the DNA and RNA from caged animals could have been a potential source of the pathogen. This center is also adjacent to the Union Hospital, where the first groups of doctors were infected during this epidemic. Curiously, the lead author has now retracted the paper saying that it was based on mere speculations and not on solid proof.

Not surprisingly, two papers posted on the websites of the Fudan University and the China University of Geosciences met a similar fate. They were removed following a new policy mandating government approval for publishing academic papers about COVID-19These clampdowns support the theory of a lab leak. The theory gets bolstered by the classified cables from the US embassy in China in January 2020.It was reported that the labs were conducting high-risk studies with a lack of appropriately trained technicians and investigators. There were concerns of undue risks being taken. Similar concerns were raised about the nearby Wuhan Center for Disease Control and Prevention lab. It appears that the leaks cannot be ruled out entirely.

An Indian paper published in January, which has now been retracted, theorized genetically altered insertions in the genome of the novel CoV similar to the genetic sequences of human immunodeficiency virus (HIV) and Ebola.They found it quite unlikely for a virus to have acquired such unique insertions naturally in a short duration. These artificially engineered changes were thought to increase the range of host cells that the 2019-nCoV can infect. This paper was taken down amidst criticism, but research from the Nankai University in Tianjin reports similar findings.This can be considered an evidence for the virus being man-made.

Lastly, the doctors who were the first responders were allegedly clamped down by the government. Li Wenliang who sounded the alarm on the Wuhan CoV on WeChat was taken to the police station where he was warned against spreading rumors. Unfortunately, he succumbed to the disease subsequently. These doctors were advised by the government, “not to mislead the public” and to “refrain from publishing any unauthorized information.” They were also told to “resist all kinds of rumors and clarify and guide false opinions and discussions."

For a pragmatic view on the issue, it is imperative on our part to look at arguments against the lab origin of COVID-19. Rhinolophus affinis bat and Malayan pangolins (Manis javanica) contain CoVs similar to the SARS-CoV-2. However, the receptor-binding domains (RBDs) of viruses isolated from these two sources were markedly different from the human SARS-CoV-2 RBDs, which have a lower affinity to the angiotensin-converting enzyme 2 (ACE2) receptors. Theoretically, this may indicate a process of natural selection in the animal host before transfer.Secondly, this adaptation may have occurred after the zoonotic transfer into the humans. A progenitor of SARS-CoV-2 after infecting humans may have acquired genomic features through adaptation during undetected human-to-human transmission.Retrospective serological studies could answer these questions. Lastly, the optimal RBD sequence for the human receptors as predicted using computer models, significantly differs from the RBD sequences with high binding affinity isolated from the humans.If artificial engineering was the source, this particular RBD sequence would not have been preferred as it did not have a high binding affinity as predicted in the computer models. This underscores the possibility of natural selection.

Nevertheless, many evidences seem to give credence to the theory of a man-made virus that has leaked from the lab into the community. Although it seems unethical to point fingers at this time when our efforts are required elsewhere, one cannot be contented with the community origin theory put forward by the Chinese government when the evidences say otherwise. It is imperative on the part of the health-care community to get to the bottom of this in order to prevent future occurrences of man-made pandemics, simply because we may never have a chance otherwise.

Books and websites consulted

• EMERGING VIRUSES: AIDS &  EBOLA  Nature, Accident or Intentional?    Tetrahedron, Inc. 1996.    Leonard G. Horowitz, D.M.D., M.A., M.P.H.  Foreward by W. John Martin, M.D., Ph.D. 

• THE GREAT INFLUENZA

• The Epic Story of the Deadliest Plague in History

• JOHN M. BARRY

Viking

• The Viral Storm Dawn of a new pandemic age by Nathan Wolfe

• https://www.crstonline.com/article.asp?issn=2590-3233;year=2020;volume=3;issue=2;spage=284;epage=286;aulast=Chaturvedi

• https://www.bbc.com/news/uk-48540653

• Origin and evolution of viruses Edited by Esteban Domingo

Virus an illustrated guide to 101 microbes MARILYN J. ROOSSINCK With a foreword by Carl Zimmer