Saturday, May 6, 2023

Pathogenesis: Placing the Human Population in a Global Perspective

We humans like to think of ourselves as masters of our destiny and as having dominion over the planet.  To counter such foolishness, Jonathan Kennedy has presented a somewhat different perspective in his book Pathogenesis: A History of the World in Eight Plagues.  He presents a fascinating and compelling retelling of our history and Earth’s history where the main players are the microbes that fashioned the planet into a platform that would allow the development of complex life forms.  We humans are the offspring of those microbes.  Having evolved in a microbial soup, these microorganisms (including viruses) are a part of who we are and have continuously altered our development and our history.

First, Earth had to be made hospitable to advanced life forms.  Oxygen provides the fuel complex life forms require.  It is a highly reactive element, and the early earth would have little free oxygen.  Our planet formed about 4.6 billion years ago.  Evidence of microbial life forms appeared about a billion years later. 

“About 2.5 billion years ago our world was almost completely submerged in water, with the exception of the odd volcanic peak piercing through the sea.  Methane in the atmosphere created a greenhouse effect that kept the planet far hotter than it is today.  There was little or no free oxygen in the water or air, as it was all locked up in other molecules.  Life on earth consisted of anerobic bacteria.  Then the world began to change with the emergence of cyanobacteria—blue-green algae that used the sun’s rays to power photosynthesis.  This made cyanobacteria much more effective at generating energy, giving them a huge evolutionary advantage.  Their numbers boomed.  Over a period of several hundred million years, they pumped vast amounts of oxygen—a byproduct of photosynthesis—into the oceans and atmosphere.”

“This Great Oxygenation Event transformed the planet.  Some of the oxygen combined with methane to form carbon dioxide, a much less effective greenhouse gas.  As the planet cooled, ice sheets crept as far as the tropics.  The sea level fell and land emerged from the water.  Eukaryotic organisms appear in the fossil record shortly after oxygen became abundant in the atmosphere.”

“Cyanobacteria in the oceans still contribute to the oxygen in the atmosphere.  In total, phytoplankton—photosynthesizing microorganisms in the sea—account for at least half of the oxygen produced by living organisms.”

The famous paleontologist, Stephen Jay Gould was moved to claim that “bacteria are—and always have been—the dominant forms of life on earth.”

“Bacteria are everywhere.  They have been found in Antarctic glaciers and on the ocean floor where boiling hot water surges out of the center of the earth.  They live miles below ground and miles above it, where they influence the formation of clouds and possibly even lightning.  They are so numerous that, despite their tiny size, the total mass of all bacteria on the planet is thirty-five times that of all the animals and 1,000 times that of all humans.”

To these microbes must be added the ubiquitous viruses that infect the microbes and all other life forms.

“Viruses are tiny, even by the standards of microbes.  They can be hundreds of times smaller than the average bacterium.  Viruses are so minuscule that they haven’t left a mark on the fossil record.  Their origins remain unclear.  They may have emerged prior to, soon after, or even from early single-celled life.  In any event, for most if not all the 3.5 billion years that life has been around, viruses have been capable of infecting it.  They are found everywhere where life is present and far outnumber all forms of life on earth—even bacteria.  A liter of sea water contains over 100 billion virus particles, and one kilogram of dried soil somewhere in the region of a trillion…But only about 220 types of virus are known to be capable of infecting humans.  Most are so-called bacteriophages or phages—from the Greek ‘to devour.’  Phages kill between 20 percent and 40 percent of all bacteria every day, which maintains balance in a variety of ecosystems, from the oceans to our own bodies, by ensuring that no one strain of bacteria can become too numerous.”

Viruses can both maintain and kill life forms.  Somewhat less recognized is the fact that they can alter life forms as well.

“A retrovirus is a specific type of virus that reproduces by inserting a copy of its DNA into the genome of the host cell.  But when a retrovirus infects a sperm or egg cell, something remarkable happens: viral DNA is then passed on to every cell in every subsequent generation.  An astonishing 8 percent of the human genome is made up of such genes.”

Much of this genetic material seems to have no function, but some of it is now recognized as being fundamental in the evolution of life.  Kennedy provides two examples of what scientists now recognize as virus-introduced genetic mutations.  The first is a mutation that occurred about 400 million years ago and provides a role in memory formation.  The removal of a single gene can render mice incapable of forming memories.  The second involves the mutation that allowed offspring to be raised within the body of a female rather than by producing an egg.  This involves creating a placenta with an interface through which the mother and offspring can exchange nutrients while not generating immune responses due to their different genetic makeup—a rather complex construct.

“When geneticists looked at the gene responsible for creating it [the placenta interface], they realized that it was almost identical to those used by retroviruses to produce the proteins that attach to cells they are infecting without triggering an immune response. The scientists concluded that a crucial function of the placenta didn’t emerge gradually as a result of evolution by natural selection but was suddenly acquired when a retrovirus inserted its DNA into our ancestor’s genome.”

This capability can be harnessed by medical researchers using viruses to deliver new genetic material into cells in the field of gene therapy.

The critical role that the microbes play within our bodies requires us to consider them as important to life as any organ upon which we depend.

“Our bodies are absolutely teeming with microscopic life.  Each of us hosts an estimated 40 trillion bacteria—meaning they slightly outnumber human cells.  Viruses? At least ten times that figure.  In total, the human microbiome—all the microbes living in our body—weighs around the same as our brain, between one and two kilos.  The vast majority of these bacteria and viruses don’t make us ill.  In fact, they have evolved with our ancestors for millions of years, forming close and interdependent relationships with one another.  In other words, humans have outsourced some essential tasks to microbes.  This is because bacteria can adapt more quickly to new situations than humans.  While our cells carry between 20,000 and 25,000 genes, the microbiome contains around 500 times more than that.  The enormous number of genes, together with the fact that they reproduce far more quickly than more complex life and are able to transfer genes ‘horizontally’ from one species to another, allows bacteria to evolve much faster than humans.”

Recognizing the critical role of microorganisms in human life drives us to rethink our history in terms of the role human initiative has played and the role microorganisms have played in forcing humans to respond to their initiatives.  We know that microbes can infect us with diseases that are capable of killing a large fraction of the human population.  That has happened numerous times throughout history.  Is it the “fittest” that survive, or those with the strongest immune response.  Do we need to reconsider the nature of evolution?  

Consider one lesson from our recent history.  European societies with dense populations and intimate relations with animal species encountered multiple deadly plagues.  People would eventually develop immunity and the survivors would propagate the society with the dangerous microbes remaining endemic within the population.  These Europeans would then arrive on the American continents and encounter indigenous populations with no experience with those microbes.  The result was enormous loss of life for the natives and a tremendous advantage for the invaders.  A small population was aided by microbes in dominating a much larger indigenous population and taking control of the continents and their future history.  This was a momentous result, but it was by no means a unique occurrence.  Microbes and the diseases they cause would play a great role in how human history evolved.  That is the subject of Kennedy’s book: illuminating how human history has depended on the vagaries of microbial interactions.  His study led him to make the following observation.

“It is no exaggeration to say that bacteria have made the planet habitable for complex life, including humans.  It’s a bacterial world, and we’re just squatting here.”

  

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