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Kindle Notes & Highlights
by
Tom Ireland
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September 11 - October 12, 2023
In 1942, the biologist Thomas F. Anderson
managed to get funding to explore biological specimens with one being built by scientists at the Radio Corporation of America (RCA).
The old master was apparently on his deathbed when he first saw an electron microscope image of a phage, years later in 1949.29 Over thirty years since he first deduced that what he had seen must be a form of replicating life – a microbe of a microbe – and after two decades of vitriolic arguments, pointless polemics and personal smears – here was something like proof.
‘ghosts’ – the empty-headed phages stuck to the outside of bacteria – and expressed a ‘wildly comical possibility.’32 Perhaps the phages injected some kind of genetic material, syringe like, into the host cell, and it was this that changed the host’s nature from thriving cell to suicidal virus factory? Around this time, other work by members of the Phage Group had determined that phages contained just protein and DNA, nothing more. And so, one of these must be the genetic material that carries the blueprint of life.
Nature winced under the onslaught of young men counting specks in Petri dishes . . . The air was filled with the phage particles that Delbrück had picked out as one of the weakest spots in the armour behind which nature guards her secrets. Over it all hovered the spirit of Delbrück, who was shepherding his handpicked band along the last stretch of the narrow path to the central fortress of biology . . .
He began referring to the old methods of biology – the endless observation, naming and cataloguing of living organisms, as ‘stamp-collecting’.
The group used scintillating logic to devise variations of virus-host experiments that would reveal the inner workings of life in the form of mathematical data.
scientific papers carrying the latter’s name ‘formed a little green island of logic in the mud-flat of conflicting reports, groundless speculations, and heated but pointless polemics that surrounded the Twort–d’Herelle phenomenon.’
‘the onset of biology as an exact science’,
the fact remained, the true abundance and diversity of phages out there in the world remained unseen and unnoticed.
Delbrück’s scientific snobbiness would come back to bite him as other scientists, including his own peers and protégés, inched closer to the great biological breakthrough of the twentieth century (and arguably, of all time).
The improvised experiment showed clearly that phages’ DNA was transferred into the bacteria during infection and nothing else.
James Watson, is now maybe as famous for making racist comments and for his misogynistic views of colleague Rosalind Franklin, as he is for his contribution to one of the most famous scientific papers in history.
In one blow, the double helix revealed the ‘secret of life’FN00 – and there was no great paradox, no new rules of physics required to explain it. It was just chemistry; chemistry so simple to understand that it, in Delbrück’s words, ‘made the whole business of replication look like a child’s toy that you could buy at the dime store’.
Delbrück
He, Luria and Hershey had essentially invented an entirely new field of the life sciences that would become known as molecular biology, which, in turn, would lead to genetic engineering, genetic medicine and a host of ever-more fantastical biotechnologies that are now changing the possibilities of biology at an unprecedented pace.
The first gene to be sequenced by scientists – that is, the exact sequence of DNA subunits in a gene deciphered by scientists – was a gene from bacteriophage MS2.
The first entire genome to be sequenced – in other words the first entire set of genes that make up an organism to be decoded – was also a phage (the super simple bacteriophage ΦX174).
Trace almost anything being done in a modern molecular biology lab back to its roots, and you’ll likely find Delbrück, Luria or Hershey. And, always, a phage.
Marine bacteria were once believed to be the most abundant form of life in the oceans, but these papers were suggesting they were outnumbered by viruses ten to one, and in some environments one hundred to one.
There are more phages in a typical litre of seawater than there are humans on the planet,
Even a teaspoon of earth from a baked desert, or ice locked into glaciers for thousands of years, can contain an active community of thousands or millions of phages.
Other research from 2022 even suggests that phages may help certain unusual rock structures form from minerals and sediments in the sea, literally shaping the very Earth itself.
whereas us higher organisms have to wait to have sex to shuffle our genes and create variation in the next generation, bacteria and viruses and other completely unrelated lineages of microorganisms are able to swap, steal and share genes that others have spent millions of years developing.
20 million billion times per second.69
20 petahertz
Phages also help transport genes for antibiotic resistance from one bacteria to another.
They also show how important it is to understand the biology of phages before we inject them into the body as medicines.
Phages can alter their hosts’ metabolism and behaviour so much that some researchers think that bacteria of the same species that have and haven’t been infected by phages might need to be considered different organisms.
viruses are our planet’s most abundant biological entity. So, if there was life somewhere else, we would be more likely to find them than anything else.’
Back in the 1920s, one of Felix d’Herelle’s more outrageous claims was that phages were an integral part of our immune system, a kind of live-in virus that our bodies had co-opted to counter bacterial infections on our behalf.
Barr’s lab in the suburbs of Melbourne is focusing specifically on what he now calls our ‘third immune system’: the ecosystem of phages that protects us from bacteria alongside our other, more well-studied innate and adaptive immune systems.
the hope that one day phages can be used to reverse or correct disorders of the gut.
This dynamic, known as ‘kill the winner strategy’, tells us that a single type of phage is unlikely to ever completely eradicate a bacterial pathogen from our bodies – but it could degrade the population to the point where our immune system, or antibiotics, or different phages, or a combination of all three, finish off the remaining bacteria and clear the infection.
this super diverse and hyper-abundant group of viruses represents the largest reservoir of unexplored genetic information on the planet. With potentially trillions of different types of phages out there, many refer to them as the ‘dark matter of biology’.
polyphyletic. This means that there is no clear ancestral lineage from which all modern phages evolved. Phages appear to have emerged and evolved completely independently from one another at many different points in the history of life on Earth.
CRISPR being used to help reverse a genetic trait that causes high cholesterol; to breed faster race horses in Argentina; to make pig organs more compatible for donation into humans; to make new treatments for cancer and genetic diseases; and even to try and make the woolly mammoth ‘de-extinct’ by
Scientists have already begun to test the safety and efficiency of editing human embryos to remove disease-causing genes, both with and without the approval of the scientific community,
‘chromosomal island’, these tiny bunches of genes have evolved to selfishly self-propagate themselves by jumping from cell to cell aboard phages when they replicate inside a host. In other words, they behave like viruses of viruses.
the race is on to become the first group to treat a patient with a fully ‘synthetic’ phage – that is, a virus that has been made from scratch from chemicals, machines and pipettes, rather than from viral material replicating inside a bacterial cell.
He’s confident they will not be fazed by the fact these are effectively lab-made viruses – a scary term for a world awash with rumours about where COVID-19 really came from.
APT is increasingly confident that they have the phages needed to tackle whatever dangerous bugs are circulating in the US and beyond. So confident, in fact, that in late 2022 the company launched a challenge to the infectious disease community: they will pay $1,000 to any researcher who has a strain of bacteria (from the CDC’s six most dangerous bacterial species, the so-called ESKAPE pathogens) that cannot be killed by phages in the APT library.
by 2050, at least ten million people will die each year from antibiotic-resistant infections.
Perhaps, as the horrors of a post-antibiotic future start to bleed into the present, some countries will decide there is no time to put every phage therapy through years of clinical trials – leaning instead on the decades of experience of the Russians, Poles and Georgians.
In one study by scientists at the University of Tel-Aviv, modified worm-shaped phages were filled with anti-cancer drugs and engineered to bind only to cancer cells. Using lab-based models of cancerous tissue, the researchers found that the concentration of the drug around the tumour cells was over 1,000-fold higher than it would be if the drug was simply released into the bloodstream without its worm-phage chaperones.14
Professor Yoon Sung Nam and his ‘Nano-Bio Interface Laboratory’ at the Korean Advanced Institute of Science and Technology has even created phage-based ‘microbatteries’, capable of storing minute amounts of charged particles, and a tiny and self-assembling device that can generate hydrogen gas from sunlight and water.
My other hope for this book was to recalibrate people’s perceptions of what viruses are. How remarkable that a structure that looks so worrying, so alien, is in fact a founding member of life on our planet
‘All the world’s a phage.’
So, I think, now, I have written pretty much everything I can about the viruses of bacteria and why they are so important, and I’ve even gone out into the world and found my own. Now it’s your turn.
