Infectious

Pathogens and How We Fight Them

John S. Tregoning

• Publisher: Oneworld Publications
• Year: 2021
• ISBN:
  9780861541232
• Topic: Tecnologia e ingegneria
• Subtopic: Scienze applicate

The human body is a marvel – but what happens when it comes under attack? A fascinating guide to why we get sick and how we get better. 'Lovely, warm, erudite and, above all, chatty.' Chris van Tulleken, author of Ultra Processed People Nature wants you dead. Not just you, but your children and everyone you have ever met and everyone they have ever met; in fact, everyone. It wants you to cough and sneeze and poop yourself into an early grave. It wants your blood vessels to burst and pustules to explode all over your body. And – until recently – it was really good at doing this…The subject of infection and how to fight it grows more urgent every day. How do pathogens cause disease? And what tools can we give our bodies to do battle? Infectious is not only a vital overview of what goes awry in our bodies, but also a hopeful story of ongoing human ingenuity.

PART 1
’Ologies: Investigating and Understanding Infectious Disease

Chapter 1

A Brief History of Microbiology

Timeline: Late March 2020. Epsom. COVID-19 spreading globally, one week into UK lockdown. Global COVID-19 cases 509,164; deaths 23,335.

‘Begin at the beginning,’ the King said gravely, ‘and go on till you come to the end: then stop.’

Lewis Carroll

In the beginning was the word and the word was soup. And not a good soup like chicken noodle or mulligatawny, but rather a primordial soup. This soup contained some really long molecules, a number of which evolved to make copies of themselves. These self-replicating molecules developed further and over time evolved into organisms demonstrating the characteristics of life: they could move, respire, respond to the environment, grow, reproduce, excrete and eat. More time passed and things got more complicated. Which is roughly where we come in as a species. Homo sapiens have walked the earth for approximately 200,000 years – an extremely long time in human terms, but nothing at all in evolutionary terms.

So we find ourselves something of a latecomer to the scene. This means we had to adapt to our surroundings to get the resources we needed to make copies of ourselves. In evolutionary biology this is called a niche. Different organisms have developed different tactics to acquire resources. Some trap energy from the sun (plants mostly), some eat plants (herbivores) and some eat herbivores (carnivores) – with a variety of strategies in between. So far, so primary school.

Critically, resources are limited, leading to competition both between and within species. Competition for resources drives evolution. When you get down to brass tacks, evolution is about the struggle to pass your genes from one generation to another. All living organisms, except maybe incels, are trying to achieve this one goal. If you are sufficiently curious, read Richard Dawkins’ The Selfish Gene, still the definitive popular science primer on evolution.1

Some organisms preferred to hitch a ride on their hardworking relatives. Rather than go to the effort of finding ways to make copies of themselves, they evolved methods of invading other cells, getting them to do the hard work. This is called parasitism. Not all parasites are microorganisms – mistletoe, for example, steals its nutrients from the plant upon which it grows. However, this book focuses on the microbiological level: specifically, how do tiny parasitic organisms threaten our whole body?

Time for a bit of terminology. Scientists are sticklers for the correct word because it avoids ambiguity. A disease is not the same thing as the thing that causes it. Disease refers to the symptoms. So COVID-19 is the un-catchy name for the disease caused by the similarly un-catchy SARS-CoV-2 virus. Disease can be infectious or non-infectious. Non-infectious diseases are also known as non-communicable diseases because you can’t catch them from someone else – common examples include heart disease, lung cancer and stroke. You get non-communicable disease through a combination of environment, genes and bad luck. Infectious diseases are caused by another organism invading your body.

The catch-all term for microbes that cause infectious diseases is pathogens. Sometimes people refer to them as bugs. They shouldn’t. Bugs live in the garden. So, from now on, call them pathogens. Pathogens are anything (living and small) that can get into your body and cause disease.

Living together: DYING TOGETHER

Our interactions with pathogens have shaped us. They have shaped our societies, our genes and our very selves.

Pathogens have had a huge influence on human history, all the way back to prehistory when pathogens like smallpox spread from the first farm animals to the earliest farmers. This interspecies movement is called zoonosis and it still occurs in the present day. HIV most likely arose in monkeys and SARS-CoV-2 probably came from bats. But before getting on your high horse about not eating wild animals or bush meat, bear in mind that influenza, which kills approximately 500,000 people every year, comes from domesticated chickens and pigs.

While infections have coexisted with humans throughout our evolution, pandemics are a feature of civilisation. The word pandemic comes from the Greek, meaning all the people. People need to be living in close enough proximity to allow the infection to spread within communities and have enough contact between communities to spread it more broadly. The first recorded pandemic was the Justinian plague. This emerged in Egypt in the year 541 ce and did not disappear until 750 ce. Pandemics accelerate societal change. The Justinian plague led to the destabilisation of the Roman Empire, creating space for other powers to emerge, including Islam. The Black Death, caused by the same bacteria as the Justinian plague, Yersinia pestis, had an even greater societal impact, killing a third of the population of Europe between 1347 and 1351.FN03

Y. pestis is just one of several infections that have altered the course of human history. The smallpox virus enabled five hundred conquistadores to annex the Aztec Empire, with a little help from their guns and horses.2 In 1520, a single pox-ridden slave from Spanish Cuba arrived in Mexico; the virus they carried cut the indigenous population from 20 million to 1.6 million by 1618.

Infections have not only shaped our societies; they have also shaped our genetics. The need to survive infections puts a selective pressure on certain characteristics. For example, the higher prevalence of malaria in Africa explains the relative frequency of the genetic condition sickle cell anaemia in people from Africa. Sickle cell disease arises from a mutation in the haemoglobin gene, which affects how people make red blood cells. Without the mutation red blood cells look like fried eggs and with the mutation they look like bananas (or sickles to be more accurate). In a world without malaria the sickle variant is a disadvantage, because the banana-shaped red cells do not flow around the body as efficiently. However, the Plasmodium parasite that causes malaria prefers fried eggs (healthy red blood cells) to bananas and so people with the sickle haemoglobin gene find themselves less susceptible to infection. Since malaria is more common in sub-Saharan Africa, individuals who don’t get infected are more likely to survive and pass on their genes to the next generation.

There are many other valid examples, but sadly I think I dreamed up the other example I wanted to use – linking a preference for tea rather than beer in the Middle Ages to the selection for the alcohol flush reaction in people of East Asian origin. If anything, evidence suggests that mutations in the gene involved in ethanol metabolism (alcohol dehydrogenase), which is associated with alcohol flush, emerged with the development of rice wine.3

Lastly, at a cellular level, humans are the offspring of host and microbe. The energy required by my brain to type this and for yours to read it is produced by a part of the cell called the mitochondria. Mitochondria are derived from bacteria in an ancient fusion event. As an aside, we only inherit our mitochondria from our mothers – hence all humanity can be traced back to a single ancestor, known as Eve, who lived in Africa 150,000 years ago. It’s not just the machinery our cells use that is bacterially derived – 8% of our DNA is microbial in origin. Basically, some viruses got lazy, set up homes in our cells and never left. These viruses, called the endogenous retroviruses, have been part of our make-up for so long we actually need their genes to function. The gene Syncytin-1, which helps the placenta develop by fusing cells together into one larger cell, is of viral origin. It has been part of our genomes for about twenty-five million years – longer than humanity’s existence as a species.

In turn, we have shaped pathogens. There is an ongoing arms race between host and infection, where both change but neither wins. The US evolutionary biologist Leigh Van Valen coined the Red Queen hypothesis to describe this race, based on the line in Through the Looking-Glass where the Red Queen says: ‘Now, here, you see, it takes all the running you can do, to keep in the same place.’

Even though infections have had a great impact on us and us on them, for most of history humans remained ignorant as to why they got sick and died. All sorts of things were blamed for illness, like bad air, the stars, cats, ethnic minorities and witchcraft. Until the eighteenth century the Greek philosophers Hippocrates and Galen influenced cutting-edge scientific thinking about infections in Europe, attributing disease to a misbalance of the four humours – phlegm, black bile, yellow bile and blood. The lack of understanding led to terrible treatments you would find only on quack websites today: bleeding, trepanning and purgatives. It was the survival of the luckiest and your health was probably improved by avoiding a doctor in the first place.

It took a long time to realise microorganisms caused infections. Yes, there was speculation about tiny organisms early in the sixth century, but given some of the other things that were believed then this feels like an infinite monkeys and typewriters situation; if you look hard enough, you can find someone who proposed the answer by accident without any evidence to support it.

Scientific progress and technological advances have always gone hand in hand: better tools lead to better science. Antonie van Leeuwenhoek, a seventeenth-century Dutch draper, refocused our understanding of microorganisms. He initially wanted to investigate the quality of the thread he sold, which led to an interest in lens making and ultimately the development of the microscope. Van Leeuwenhoek’s microscope enabled him to see organisms invisible to the naked eye. He observed a whole range of different single cells in blood, pond water and semen (because you would, wouldn’t you).

The demonstration by van Leeuwenhoek that single-celled organisms existed unlocked understanding about their role in disease. Two Germans and a Frenchman, Cohn, Koch and Pasteur, built on this knowledge to lay the foundations of bacteriology in the nineteenth century. Ferdinand Cohn worked at Breslau University (now Wrocław, Poland), where he used a microscope that had been given to him by his father. Being the only researcher at the university to own a microscope gave Cohn a considerable advantage – it would be like turning up to university today with a particle accelerator and a super-computer. Using his unique instrument, Cohn was the first to identify bacteria as a separate class of organism.

Louis Pasteur, he of ‘milk is the fastest drink’ fame (for this and other terrible loosely scientific dad jokes see footnote),FN04 was a French polymath who initially started as a chemist, exploring the shapes of chemical molecules. He discovered a property called chirality, which means that individual molecules of the same substance can fold into different mirror image conformations. These different conformations of the same molecule are described as left- and right-handed forms – technically L (laevo – left) and D (dextro – right). Like your hands, chiral molecules reflect each other but cannot be overlaid. Chirality has an incredible impact on drug design: just as only a right hand will fit into a right glove, only some drug orientations will match their target. This means that when you make a drug you need to be careful which orientation you get...