Monday, July 6, 2020

Nazi killer viruses. Communist virus phobia fake news. Phages: their role in bacterial pathogenesis and biotechnology

Go to the beach
Spread viruses
Get a suntan to stay healthy.

Viruses are your friend,
your body is filled with viruses as part of your immune system.
Viruses destroy bacteria and fungi that can kill you.
There are more viruses, fungi and bacteria inside your body than cells of your body.
Most of your genetics are viruses and bacteria inside you.

Nazi soldiers carried bottles of viruses into battle to fight infections.
Virus treatments (bacterio-phages) have been studied over 100 years.
You can be treated today in San Diego, University of California a leading center.

Super-bugs are not treatable by antibiotics, so viruses are used to treat.
MRSA staph is what my father got in 1985 until UCLA saved him.
(Multi drug Resistant Staphylococcus Aureus.)
It is everywhere nowadays especially around Cows, pigs, chickens...

Virus phobia is a Communist Plot to sicken America,
Terrorize the population,
Influence elections,
Take over the government.
Lockdown disease,
Electronics addiction,
tobacco addiction,
alcohol addiction,
drug addiction,
fake news,

Replace the American Population with
negro slaves,
latino slaves,
muslim slaves,
pig shit factories,
pesticide GMO plantations,
to make pork CAFO for Communist China.
Not surprising the virus came from China!
More is coming.

Viruses are small and inject genetic material into the big bacteria that hijacks the replication chemicals to make thousands of copies of the viruses and explode the bacteria


Did you know that standard German war medical kits captured in North Africa from Rommel's forces
contained vials of phages
ready for injection or oral administration?

Phages: their role in bacterial pathogenesis and biotechnology

Any book that contains the phrase "rolling global‐scale orgy of bacteriophage sex" will grab my attention,
, I am a bacteriophage enthusiast.

I'm really only an amateur and this book is primarily for the professional enthusiast,
and at $120, it is likely to be read only by those who work with bacteriophages regularly.

This is a shame, as it contains some fascinating material.
Did you know, for instance, that, with a total population estimated at any one time to be 1031,
phages are the most numerous organisms on the planet?
I didn't know until I read this book.

Another amazing fact that had me firing off emails to my long‐suffering colleagues was that if all 1031 of these phages were laid end to end,
they would extend into space to a distance of 200 million light years!

I bet all the busy district general hospital pathologists who chance to read this review are now muttering to themselves about how teaching hospital microbiologists can waste their time writing about such irrelevant things, but in fact bacteriophages are important and I'll try to explain why.

Much of our current knowledge of molecular biology owes its origins to the pioneering work of early phage researchers such as Max Delbrück, Salvador Luria and Joshua Lederberg.

This book reviews the work of these early pioneers, but more importantly brings the story of bacteriophages up to date. Individual chapters are written by the recognised experts in the field, and review basic phage biology and ecology.

The major part of the book contains chapters describing all the latest developments on the topic of phage contribution to bacterial virulence.

Phages play an extremely important part in allowing relatively harmless bacteria to become pathogens.

In fact, up to 6% of the genome of Salmonella typhimurium is believed to be made up of prophages.

Most of the examples described in these chapters are virulence‐linked bacteriophages such as the phage CTXφ, which encodes cholera toxin in Vibrio cholerae, or the phage β, which encodes toxin production in Corynebacterium diphtheriae, but there is also a fascinating chapter on phages and bacterial vaginosis in which the phage acts in an entirely different way.

This book provides evidence that phage infection in vaginal lactobacilli may cause a decrease in these important commensal bacteria, resulting in the shift in vaginal bacterial numbers that is thought to cause bacterial vaginosis.

It is proposed that these phages may be acquired sexually or that lysogenic phages already present in commensal lactobacilli may become lytic as a result of exposure to environmental chemicals such as those found in cigarette smoke.

Bacterial vaginosis is known to be more common in smokers.

Some researchers have even suggested calling the disease "bacterial phaginosis".

Some of the chapters on virulence also give details of the use of phages in bacterial detection or as therapeutic agents.

Also included are some interesting descriptions of the therapeutic uses of phage products rather than the whole phage—for example, the enzybiotic murein hydrolase.

The last chapter of the book describes the utility of phages in greater detail, such as their use in recombineering and in molecular display libraries.

A final and relatively short chapter describes the use of phages in bacterial detection and as therapeutic agents.

Although similar information is found in other sections of the book, this final account complements the opening chapter of the book, which describes some historical details of phage therapy.

To conclude, I think this is an excellent book, although it will be of major interest only to established phage biologists and those interested in the mechanisms of bacterial virulence.

However, I can also recommend it to like‐minded amateur phage enthusiasts.

Finally here's a question for you.
How many phages are there in 1 ml of Norwegian fjord water?
I'm not going to tell you, but if you want to know the answer, you now know where to find it!ück

1969 Nobel Prize in Physiology or Medicine
"for their discoveries concerning the replication mechanism and the genetic structure of viruses".

Delbrück was born in Berlin, German Empire.
His mother was granddaughter of Justus von Liebig, an eminent chemist,
while his father Hans Delbrück was a history
professor at the University of Berlin. In 1937,
Delbrück left Nazi Germany for America—first California, then Tennessee
—becoming a US citizen in 1945

He was the first physicist to predict what is now called Delbrück scattering.

The phage group (sometimes called the American Phage Group) was an informal network of biologists centered on Max Delbrück that contributed heavily to bacterial genetics and the origins of molecular biology in the mid-20th century.

The phage group takes its name from bacteriophages, the bacteria-infecting viruses that the group used as experimental model organisms.

In addition to Delbrück, important scientists associated with the phage group include: Salvador Luria, Alfred Hershey, Seymour Benzer, Gunther Stent, James D. Watson, Frank Stahl, and Renato Dulbecco.

Bacteriophages had been a subject of experimental investigation since Félix d'Herellehad isolated and developed methods for detecting and culturing them, beginning in 1917.

Delbrück, a physicist-turned biologist seeking the simplest possible experimental system to probe the fundamental laws of life,
first encountered phage during a 1937 visit to T. H. Morgan's fly lab at Caltech.

Delbrück was unimpressed with Morgan's experimentally complex model organism Drosophila, but another researcher,
Emory Ellis, was working with the more elementary phage.

During the next few years, Ellis and Delbrück collaborated on methods of counting phage and tracking growth curves;
they established the basic step-wise pattern of virus growth
(the most obvious features of the lytic cycle

Emory Ellis (1906–2003) and Max Delbrück (1906–1981)
In a retrospective article,
Emory Ellis stated "Soon after Max Delbruck arrived at the Caltech Biology Division, intent on discovering how his background in physical sciences could be productively applied to biological problems,
I showed him some step-growth curves.

His first comment was 'I don't believe it.'"
However as Ellis describes,
Delbruck soon dispelled this initial reaction of disbelief by his own analysis of the phenomenon, and promptly joined in the work with enthusiasm,
bringing to it his training in mathematics and physics, and intense interest in genetics.
Their initial collaborative findings were published in 1939.

Salvador Luria (1912–1991) and Alfred Hershey (1908–1997)
The phage group started around 1940, after Delbrück and Luria had met at a physics conference.

Delbrück and Salvador Luria began a series of collaborative experiments on the patterns of infection for different strains of bacteria and bacteriophage.

They soon established the "mutual exclusion principle" that an individual bacterium can only be infected by one strain of phage.

In 1943, their "fluctuation test", later dubbed the Luria–Delbrück experiment, showed that genetic mutations for phage resistance

in the 1920s and 1930s, and there were extensive attempts to use the phenomenon to fight infections.

Whereas it eventually became a crucial tool for molecular biology,
therapeutic uses of 'phage' declined sharply in the West after World War II,
but persisted in the Soviet Union, particularly Georgia.

Increasingly isolated from Western medical research,
Soviet scientists developed their own metaphors of 'phage', its nature and action, and communicated them to their peers, medical professionals, and potential patients.

In this article, I explore four kinds of narrative that shaped Soviet phage research: the mystique of bacteriophages in the 1920s and 1930s; animated accounts and military metaphors in the 1940s; Lysenkoist notions on bacteriophages as a phase in bacterial development; and the retrospective allocation of credit for the discovery of the bacteriophage during the Cold War.

Whereas viruses have been largely seen as barely living, phage narratives consistently featured heroic liveliness or 'animacy', which framed the growing consensus on its viral nature.

Post-war narratives, shaped by the Lysenkoist movement and the campaigns against adulation of the West, had political power—although many microbiologists remained sceptical, they had to frame their critique within the correct language if they wanted to be published.

The dramatic story of bacteriophage research in the Soviet Union is a reminder of the extent to which scientific narratives can be shaped by politics, but it also highlights the diversity of strategies and alternative interpretations possible within those constraints.

Through the course of the twentieth century, bacteriophages have been crucial scientific objects for microbiology, virology, electron microscopy, and molecular biology.

Recently, their therapeutic uses against bacterial infections have been receiving much attention and hope, as concerns over antimicrobial resistance intensify.

But phage therapy is not new—it is almost as old as d'Hérelle's coinage of the term bacteriophage in 1917, and was one among the diverse methods of treating and preventing infection between the world wars. While largely abandoned in the West after World War II, phage therapy persisted in the USSR, particularly Georgia, where a dedicated institute devoted to bacteriophage research and therapy was founded in the 1930s, and exists to this day as the Eliava Institute of Bacteriophage, Microbiology, and Virology.1

This article explores the narratives of life, death, and viruses in Soviet bacteriophage research and the histories of the field that Soviet scientists told. While following debates in Europe and the USA, Soviet microbiologists developed unique perspectives on bacteriophages, which were strongly shaped and constrained by political pressures. In the beginning of the Cold War, the campaign against 'cosmopolitanism' and the rise of Lysenkoism caused striking departures in biological thinking, but Soviet discussions also had a specific flavour in earlier periods. The mysterious nature of a phage, a 'substance with creature features',2 and its liminal position between life and non-life made it a fascinating subject and acted as justification for continuous research. Its therapeutic and diagnostic applications, such as phage typing (see Kirchhelle, this issue)3, appealed as an example of Marxist science, as phage research combined important theoretical questions with practical applications for the benefit of the Soviet state. Whereas institutional factors were crucial in the survival of phage therapy alongside phage research, the way in which phages were discussed and framed also played an important role.

In analysing the narratives of bacteriophage, I pay special attention to discussions of life and death, and to the language used to describe phages. I am inspired by work on metaphors in science, especially Luis Campos's study of radium as a lively substance—in the first half of the twentieth century, the element was often interpreted as living, owing to its radioactive decay.4 Similarly, even though Soviet scientists disagreed over whether phages were living or dead, they continued to be discussed as active agents. In the 1940s, with phage therapy used extensively in the war effort, the framing of phages acquired a strongly militaristic flavour.

Rather than simply asking whether phage had agency in analytical terms, I broaden my examination of phage discourses by drawing on queer theorist Mel Chen's analysis of 'animacy' to examine the discourses surrounding phage. Animacy, a concept Chen borrows from linguistic anthropology, is in the first instance a grammatical term, which refers to the likelihood of a noun to be treated as a sentence subject rather than object. Languages and discourses, Chen argues, establish hierarchies of animacy, which do not always map onto the living–non-living binary, but often reveal bias on racial, gender, or other lines.5 As I show, despite the equivocal categorization, numerous accounts that made sense of bacteriophages, whatever stance they took, endowed them with animacy and strengthened the argument for phages as living parasites of bacteria. In particular, two different ways of framing phage animacy in the 1950s—an independent virus or a 'filterable form' in bacterial development as some Lysenkoists would have it—had consequence not only within the politics of Soviet microbiology, but also in practical terms.

Framing the discussion in terms of narratives allows a more flexible account of scientific ideas and how actors made them cohere, as well as their communication and transit, and their interaction with political and practical worlds of science. Focusing on narratives serves as a reminder that peculiar conceptualizations of phages in the USSR went beyond metaphors—scientists and physicians made strong ontological claims about what phages were, they gave accounts of their reproduction or lack thereof, they produced and reproduced images to make and challenge visual arguments, and they questioned discovery accounts.6 In addition, lively narratives influenced practice, as ideas about the nature of phage enabled different experimental interventions and research programmes. Although a detailed account of the practice of phage research is beyond the scope of this article, I offer some examples of phage production during the World War II, and hint at the difference between the practical worlds of Lysenkoist researchers and microbiologists at the Tbilisi Institute.7

This article proceeds chronologically while highlighting four kinds of narratives. First, it examines the mystique of phages in the 1920s and 1930s, and the productive role it played in establishing infrastructures and securing research funds. I then examine animacy in the accounts of bacteriophage therapy during the USSR's Winter War with Finland (1940–1941), and during World War II, which the Soviet Union entered when Nazi armies invaded in June 1941. In the post-war years and the early Cold War, Lysenkoist accounts of reversible transformation between bacteria and viruses created a new framework for biologists to work with, and even those critical of the idea needed to make their arguments comprehensible through these dominant narratives if they were to be published. Finally, I examine the official Soviet narratives of the discovery of bacteriophages during the Cold War period—narratives that remained unstable as credit needed to be allocated to Soviet rather than Western scientists, but not to those who had been executed or imprisoned in Stalin's terror. In particular, the complex dynamics of credit and memory played out in the commemoration of Giorgi Eliava, the founder of the Tbilisi Institute which now carries his name. The dramatic story of bacteriophage research in the Soviet Union is a reminder of the extent to which scientific narratives can be shaped by politics, but it also highlights the diversity of strategies and alternative interpretations possible within those constraints.

The phage mystique

Félix d'Hérelle's reports on bacteriophage—referring to both the phenomenon of destruction of bacterial colonies and a putative responsible agent—were first published in 1917, the year of the Russian revolution, but despite the chaos of the civil war they attracted much interest within a few years.8 In the 1920s, the new Soviet state embraced microbiology and invested in creating socialized health and expanding its network of bacteriological surveillance. The Pasteur Institute in Paris, where d'Hérelle made his observations, played an important role not only as an inspiration for new Soviet bacteriology, but also because a number of prominent Soviet scientists had spent time there. One example of such a visitor was Nikolai Gamaleia, who had published on spontaneous lysis of anthrax bacilli—a precursor to d'Hérelle's observations—in 1898, and pursued new work on the phenomenon in the 1920s.9Giorgi Eliava, a Georgian physician and bacteriologist, had established direct contact with d'Hérelle during an extended visit to the Pasteur Institute in 1918–21 and became a key proponent of bacteriophage research.

Ever since d'Hérelle's announcement, debates raged over the nature of bacteriophage, and whether or not it was 'alive'.10 Its failing to function outside of living bacterial cells suggested an inanimate nature, but its ability to reproduce indicated quite the opposite. Dilution experiments suggested that phages were corpuscular, but some preferred to view them as disorders of bacterial cells. D'Hérelle and his allies believed the agent to be a 'filterable virus', a parasite of bacteria that could pass through the finest bacteriological filters. Jules Bordet and many others argued for its enzymatic nature and origin within the bacteria instead.11 In the 1920s and 1930s, debates in Russian largely mirrored the literature in French, English and German, but a few scientists had more unusual ideas—for example, Gamaleia believed phages to be minute desiccated bacteria, although he abandoned this hypothesis in the 1930s.12

While biologists everywhere spent much energy on writing about what life meant, especially when communicating to broader audiences, questions of life, death and immortality had a particularly strong and distinct appeal to Soviet 'visionary biology' in the 1920s. Anabiosis, rejuvenation, mysterious rays, and sustained life of isolated organs featured prominently in scientific discussions, brochures, public lectures, and the booming genre of science fiction.

Debates on bacteriophages, although not as prominent as these other themes, reflected some of that fascination. Alexander Oparin, the key figure in speculations on the origins of life from organic molecules, suggested that phages could be fragments of the primordial cells.14

Vladimir Vernadsky, a visionary geographer and author of the 'biosphere' concept, speculated that bacteriophage was the smallest unit of life, and thus had the highest velocity of spreading 'biogeochemical energy'.15 Nevertheless, whether phages were living or not, and what definitions of life should be used, remained contested and mysterious. In the first original Russian monograph on the subject aimed at a broad readership of biologists, the microbiologist Sofya Kazarnovskaya concluded with a phrase borrowed from her senior colleague Georgy Nadson:

bacteriophage was a 'substance with creature features' [veshchestvo so svoistvami sushchestva].16

Meanwhile, even as these lively debates unfolded, several groups of Soviet microbiologists adopted phage for more pressing practical needs, and following d'Hérelle's example, pursued phage therapy against a number of diseases, including cholera and dysentery.

After some pioneering work in Soviet Ukraine in the early 1930s, led by Moisei Mel'nyk and Hnat Ruchko in Kharkiv, bacteriophage research and therapy acquired a solid footing when d'Hérelle himself visited the USSR twice in the winters between 1933 and 1935. Although he was offered his own institute in Moscow, d'Hérelle opted for the milder Georgian climate where he could work with Giorgi Eliava.

Eliava was a major figure in Soviet bacteriophage research, and, though he published relatively little, his work as a science organizer and manager proved essential to the expansion of bacteriophage research in the Soviet Union. By recruiting as honourable a guest as d'Hérelle, and offering arguments for new treatments—especially for 'war infections' such as dysentery and typhoid fever—Eliava managed to secure funding for the major expansion of his Tbilisi Institute into the All-Union Institute 'Bacteriophage' in 1935.

But just as construction on the building commenced in 1937, Eliava was arrested and executed in the early wave of Stalin's reign of terror. His wife Amelia was also executed, and his adopted daughter Ganna arrested and eventually sent to a prison camp in Kazakhstan.17

Bacteriophage research and microbiology more generally gave ample material for the agents of the People's Commissariat of Internal Affairs (NKVD, which became the KGB) to frame their suspects using extensive paper trails and fabrications that accompanied the arrests.

Eliava was accused of Georgian nationalism and espionage, recruiting anti-Soviet allies among fellow microbiologists, and various projects of sabotage—faulty bacteriophage and vaccines, poisoning wells with infectious agents, and preparations for bacteriological warfare.

In Soviet Ukraine, both Mel'nyk and Ruchko were executed, with similar accusations of nationalism and sabotage

But the infrastructure investment and growing military needs outweighed any suspicion of phage therapy as such.

In 1939, Zinaida Ermol'eva, a microbiologist at the flagship All-Union Institute for Experimental Medicine (VIEM) in Moscow, made a case for further research into bacteriophages as a pivotal biological problem with clear practical applications. Her suggestions appealed to military authorities, embarking on campaigns to invade Eastern Poland and then Finland, in accordance with the secret protocol of the Molotov–Ribbentrop pact between the USSR and Nazi Germany.

Military metaphors

It was during the Winter War with Finland (1939–1940) that bacteriophage therapy was tested against wound infections.

The trials were conducted by a Tbilisi team headed by the surgeon Alexander Tsulukidze, and Leningrad microbiologists led by Magdalina Pokrovskaia, who had experimented with plague phages in the 1930s.19 In their accounts of these trials, which they deemed a qualified success, as well as in medical guidance and patient diaries and memories, bacteriophages are mostly treated as another medicine.

Available as liquid solutions and sometimes as powder during the Winter and Great Patriotic Wars, phages acted as substitutes for sulfa drugs and later penicillin, neither widely available in the USSR during World War II.

Yet, when it came to the nature and action of phages, another pattern emerges from the discussions in these papers. Most authors declared uncertainty over the nature of phages, but the language they used to discuss the mysterious agent was highly animated.

Military metaphors were nothing new in bacteriology, and by no means unique to the Soviet context.

Discussion of germ theory and immunity abound with images of battles, infiltration, counterattacks and victories.

Promising antimicrobial drugs such as salvarsan and later penicillin were famously described as 'magic bullets'.20 But whereas medicines such as penicillin or gramicidin were usually analogous to weapons, bacteriophages came with more elaborate and animated metaphors.

They were variously described as agents, spies and armies that destroyed bacterial cells from within, even by authors who were uncertain as to their nature.

As a collaborator of Eliava and D'Hérelle, Tsulukidze shared their idea about the viral nature of phages.

Without any qualms, he declared that studies on the phenomena came to 'certain conclusions': that bacteriophage was a 'living principle' [zhivoe nachalo], a 'filterable virus', an obligatory parasite of bacteria with a corpuscular structure.

With this picture in mind, it is not surprising that Tsulukidze described bacteriophage in language suggesting clear agency: it 'dissolved' or 'lysed' bacteria and it 'reproduced'. Bacteria, in turn, were 'infected' by bacteriophage and were either destroyed or 'became "ill", non-viable, and lost their virulence'.21

Tsulukidze's Leningrad colleagues in the Finland War trials, led by Magdalina Pokrovskaia, were far more equivocal about the nature of phage, citing D'Hérelle's virus model but treating it as unproven.

Accordingly, in their writing they discussed bacteriophage as a phenomenon and a substance with 'viability', specificity and 'virulence', but, when presenting d'Hérelle's views, relied on curious metaphors. Bacteriophage thus 'stuck' to the bacterial surface, then 'infiltrated' [pronikaet] and started to produce a special enzyme called lysin.

As a result, new 'young' bacteriophages were freed from the cell as 'embryos' [zarodyshi].22

They could also be 'gradually trained' to adapt to different environmental factors, such as higher temperatures.23

Overall, Pokrovskaia et al. shared the 'substance with creature features' perspective, expressing hope that better understanding of bacteriophages could 'fill the void which still lies between living and dead nature.'24

Similar ambiguity over phage animacy showed itself in discussions of the practice of phage research.

Whereas in many ways phage solutions were treated as a chemically or biologically derived medicine—in terms of storage, dosage, delivery regimen—other practical interventions implied living agents interacting with the bacteria they destroyed. Involvement of d'Hérelle's private laboratory in phage production and his strong views on recommended protocols, based on the assumption of phage as a living bacterial parasite, had an effect.

Thus, Pokrovskaia suggested that the 'virulence' of a low-efficiency phage could be improved if it were passag

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