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The best books on Viruses

recommended by Dorothy H. Crawford

Viruses: A Very Short Introduction by Dorothy H. Crawford

Viruses: A Very Short Introduction
by Dorothy H. Crawford

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Many of us have developed a new fascination for viruses and virology during the global COVID-19 crisis. Here, Dorothy Crawford, professor of medical microbiology and the author of Viruses: A Very Short Introduction, selects five of the best books on viruses for the general reader.

Interview by Cal Flyn

Viruses: A Very Short Introduction by Dorothy H. Crawford

Viruses: A Very Short Introduction
by Dorothy H. Crawford

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Thank you for compiling this great reading list on viruses. Before we get onto the books, however, I want to ask a most basic question. What is a virus?

They are literally just a piece of genetic material inside a protein shell. So they’re obligate parasites. They can’t exist on their own. Whether or not they are alive is a moot point: it’s something that I’ve argued both for and against in my own books, because it’s an interesting question not only scientifically, but also philosophically. You have to start by asking: what do we call ‘alive’?

I would come down on the side of no, they are not living. After all, they don’t metabolise, so they can’t generate energy or make proteins; in fact they can’t do anything on their own. That piece of genetic material has to get inside a living cell – then it hijacks all the mechanisms of the living cell to produce its own offspring.

I see. All software, no hardware. Computer viruses are very well named, then. They do exactly the same.

Yes, absolutely.

Why did you become so interested in viruses and virology?

That’s quite an involved story. I qualified in medicine first – basically because my parents, who were both doctors, told me that’s what I was going to do. But when I qualified, I discovered that I didn’t actually like clinical medicine because I was rather shy and shunned the interaction with patients. So I started training as a pathologist.

We’re talking about the end of the 1960s. Virology was hardly a subject – it wasn’t separated from bacteriology and there were very few people who were trained in it. After I trained for a couple of years in general pathology, the bosses thought I seemed to have an aptitude for research and suggested I go and study for a PhD. I was in Bristol at the time, so I worked for my PhD in the research labs of – now Sir – Anthony Epstein, who had discovered the Epstein-Barr virus. There I became absolutely fascinated, not only with the Epstein-Barr virus, but with viruses generally.

Virology is all over the news at the moment. The novel coronavirus, COVID-19, has sent medical researchers scurrying to the labs. But how much do viruses have in common with each other? I assume they aren’t starting from scratch.

No. Let me put it this way: no virus is actually new. They’ve all come from somewhere, and usually jump to humans from other animals. All the recently emerged ones – Ebola, Lassa fever, SARS-CoV-1, flu – have come from animals, and this one is no exception. It is new to humans as far as we know, but, as we also know, it probably jumped to humans from a bat, perhaps via an intermediate host.

So, yes, viruses behave in a somewhat similar way to one another, but when you get down to the genetic level they are not similar. Some have a DNA genome and others have an RNA genome. Coronaviruses are RNA viruses like flu and Ebola viruses. So, although SARS-CoV-2 – which is the correct virological nomenclature for the new coronavirus – doesn’t have much in common at the genetic level with, say, herpes viruses, which are DNA viruses, it is 85% identical to SARS-CoV-1 that caused the SARS epidemic in 2003.

Could you tell me a little bit about the first book that you want to talk about? This is The Coming Plague: Newly Emerging Diseases in a World Out of Balance. It was first published in 1994.

Yes. And it is very much a book of its time. Laurie Garrett is a journalist, so this is not strictly a scientific book about viruses, but it’s about the human behaviours and social conditions that encourage emerging infections. She was onto the fact that the infections we catch are not just down to bad luck. It’s the things we do and the way we live that are mainly the problem. So, if we altered our way of life, perhaps we could prevent these infections. For example, a third of the world’s population drink contaminated water by necessity, and obviously this predisposes to diarrheal diseases. Yet governments in wealthy countries appear to be doing very little to improve the situation.

Garrett draws the human population explosion and increasing urbanisation together with the fact that microbes can spread much more easily when people are crowded together. Of course, this is true of SARS-CoV-2 at the moment; the more people that are crowded into confined spaces, the more these viruses are going to have a field day. She’s pointing out that epidemics are at least partly due to our lifestyle, and that there are things that we could do to prevent them. We just don’t take epidemics seriously until they happen.

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At the time The Coming Plague was published, it was a big eye opener and it became a bestseller. People were talking about it but people in westernised, wealthy countries didn’t do anything about it. This is highlighted again by the SARS-CoV-2 pandemic. Basically, if governments don’t see a pandemic as an immediate threat, not only do they not prepare, they don’t help other countries to prepare. I think people in rich, westernized countries always imagine that these things are just not going to happen to them. Until quite recently that may have been true. But with rapid air travel, you can get from one side of the world to the other in 24 hours, unwittingly carrying a microbe with you. So any epidemic anywhere in the world is a global issue.

The Coming Plague came out just when I was writing my first book about viruses, The Invisible Enemy: A Natural History of Viruses, and it certainly stimulated me to get on with it.

A very timely title. I saw Donald Trump using that exact phrase, ‘the invisible enemy,’ yesterday.

Yes, I think I should have him for plagiarism!

Consider it marketing… So, even thinking entirely in terms of our own personal benefit, it makes sense for wealthy countries to invest in public health measures to prevent the spread of viruses, novel or otherwise.

Certainly that’s the message. However, you can repeat it ad infinitum. Governments tend to be so short term they’re generally only looking to fund what’s likely to be important in the next five years. If they can put it on the back burner, they will, and with pandemic preparedness they generally do. So it is disappointing that the West was not better prepared for the COVID-19 pandemic, but not surprising.

Even when COVID-19 started in China, nobody in the West took it very seriously. If we’d started preparing for it right then, in December last year, then we might be in a better position now.

Very worrying indeed. If Garrett talks about a coming pandemic, our next book looks at the pandemics of the past. This is Plagues and Peoples by W H McNeill; this was a landmark book when it was first published in 1976.

Yes indeed. It’s an absolutely wonderful book. It’s thought provoking, beautifully written, and has stood the test of time – more so than the book we’ve just been discussing. McNeill is an academic historian, and he updated the book when HIV came along, so it’s reasonable up to date.

It highlights human interactions as important milestones in history. The one that really caught my imagination was the European invasion of the Americas. I was fascinated by events that began in 1492, when Columbus arrived in America. At that point, the Americas had been isolated for around 14,000 years. The first humans arrived in America over a land bridge between Siberia and Alaska. But that land bridge disappeared as the sea level rose after the Ice Age; it became flooded by what is now the Bering Strait. So, these Native Americans were isolated from other human contact until the arrival of Columbus.

Thereafter Europeans poured into the Americas looking for commercial opportunities – from growing sugar cane to plundering gold. Of course, the Europeans brought with them loads of infectious diseases – all the childhood infections, measles, mumps, rubella and, most notably, smallpox – all of which native Americans had not experienced. So this human interaction was disastrous for them.

“Cortés and his band unwittingly infected the Aztecs with smallpox, and masses of them were ill and dying by the time he conquered them”

Cortés fought and conquered the Aztecs in 1521, and his victory was greatly aided by smallpox: he and his band unwittingly infected the Aztecs with smallpox, and masses of them were ill and dying by the time he conquered them. Similarly, the Incas were virtually wiped out by the disease. These are the events that you don’t find in the history books. It’s mind blowing, really, that a whole population could be decimated like that. But they’d never met these diseases, so they didn’t have any immunity. Neither did they have the in-built genetic resistance that Europeans had generated by centuries of exposure to the microbes. In his book, McNeill says that the Native American population dropped from 30 million to 3 million within 50 years of Cortés arriving. Just absolutely devastating.

Until McNeill’s book was published, people very much underestimated the power of microbes. I mean, maybe Cortés and Pizarro would have conquered the Native American populations anyway, but at least they wouldn’t have been almost totally wiped out, as they appear to have been. So yes, I love that book. It’s brilliant. And my own book, Deadly Companions, is a similar historical account, but much more from the point of view of the microbes.

You mentioned that Plagues and Peoples was updated in 1989. How much has our relationship with viruses changed since then? Have medical research and virology improved our defences against them?

I don’t think it has changed much since he updated the book, to be honest. If anything, the threat has worsened, because of what Laurie Garrett was saying: our population has totally exploded. Any crowded urban situation is absolutely ideal for viruses to jump from person to person. The incidence of emerging infections has increased over the years and is still increasing. We can expect around one a year now. Most of them are not going to go global like SARS-CoV-2, but they are there, and yes, they’re getting worse.

We do have a few antiviral compounds which work, particularly against HIV, but generally only against one type of virus. That’s the problem. We don’t have anything for viruses like penicillin, that is active against many different types of bacteria. So we generally have to rely on vaccines to prevent rather than cure virus infections. And again, it’s the short term planning that’s the problem. For example, scientists had made a prototype vaccine against Ebola before the 2014-16 outbreak, but commercial companies were not interested in manufacturing it because not enough people get infected with Ebola virus to make it worth their while. Academic units had gone as far as they could with the prototype vaccine, but when Ebola appeared again in 2014 it wasn’t ready for use in the field.

Let’s move on to our next book about viruses. You want to discuss The African Aids Epidemic: A History by John Iliffe. It’s pitched as a slim and accessible account of this epidemiological disaster. Why do you recommend this book?

I chose this book because it is a very thorough account of the devastation the HIV pandemic caused in Africa. Many accounts of HIV, particularly in the 1980s, tended to concentrate on the virus’s effects in the West, where it predominantly affected the gay population but meanwhile it was silently spreading through Africa, just as Iliffe describes.

In fact, we now know that HIV first infected humans in Africa sometime before 1959 – the date of the first case that has been retrospectively identified. My book Virus Hunt is about the hunt for the origin of HIV, an amazing scientific detective story, in my opinion.

Kinshasa, the capital of the Democratic Republic of Congo, is the epicentre of the HIV pandemic from where all chains of infection began. It was recognised quite early on that HIV jumped from chimpanzees to humans, so the question was, how did it get to Kinshasa?

“The hunt for the origin of HIV is an amazing scientific detective story”

To answer this, scientists in the US and UK compared the genetic code of HIV with that of similar viruses found in African primates. Eventually, they found the virus most closely related to HIV in a single group of chimpanzees living in the southeast corner of Cameroon. So that’s where the virus transferred to humans. They postulate that the virus must have been transported down the local Sangar River, a branch of the Congo River, inside one or more infected people, all the way to Kinshasa. Given the chaos of Kinshasa at the time, it was an ideal place for the virus to thrive. It took off, spreading by heterosexual contact to cause an epidemic in the city and beyond before it had even been discovered.

Then, in around 1966, one single person carried the virus from Kinshasa to Haiti, in the Caribbean. At the time, Haiti was a place where American gay people used to holiday. So the virus entered the gay population and travelled to the US and from there it spread globally. The fact that in Africa HIV is a heterosexual infection while in many western countries it remains mainly in the gay population and IV drug users is all down to chance.

Yes. It’s frightening, the way sheer bad luck plays such a major role in how an outbreak will unfold. We saw this more recently, as part of the contact tracing of COVID-19. A single undiagnosed carrier in South Korea, for example, single-handedly infected more than a thousand others at church in Daegu. Random movements of individuals can have a disproportionately huge impact; it reminds me of the butterfly effect.

Iliffe is a professor of modern African history at Cambridge. Why is it so important for virologists and epidemiologists to understand the history of viruses, as well as the science?

There is a lot that can be learnt from each pandemic and epidemic once the full facts are known. It will probably take years before we have unravelled the emergence of SARS-CoV-2, but it is important for future epidemic and pandemic prevention to know exactly which animal it came from, the nature of infection and spread in that animal species and, of course, how it jumped to humans. Only then can we hope to prevent another such disaster.

On to our next book on viruses: this is an autobiography called No Time to Lose by the ‘virus hunter’ and professor of global health Peter Piot. He worked on this book with the writer Ruth Marshall.

Yes, Peter Piot founded UNAIDS and later became the director of the London School of Hygiene and Tropical Medicine, where I have worked in the past. He’s a very well-known and respected virologist. This book helped me with my own book Ebola: Profile of a Killer Virus, which I wrote during the 2014-16 epidemic.

It is a marvellous, scientific autobiography. Basically, Piot trained in virology at the Prince Leopold Institute of Tropical Medicine in Belgium in the 1970s. While he was training, some samples came in for analysis from Zaire, as it was then – now the Democratic Republic of Congo. It turned out that in a remote village people had come down with a ghastly disease which was deadly. In the book, Piot tells of the urgency of the situation, and the challenges of the work. He describes the everyday life of this lab, receiving samples and isolating virus from them – no protective clothing whatsoever, just handling the samples on the bench. It’s unbelievable. I’m amazed none of them caught Ebola.

Anyway, after that a United Nations commission went out to this village in DRC, called Yambuku, to work out where the virus had come from and how to prevent another outbreak. Piot was part of that commission. The village is near the Ebola River – so they called the virus Ebola as they thought calling it after the village would stigmatize it (rather like Trump’s attempt to call the new coronavirus the Wuhan or Chinese virus).

Piot describes his arduous trip through the bush to get to Yambuku and the devastating scene that met him. Then they airlifted in Land Rovers and equipment and did a full epidemiological study, visiting every family that had experienced the disease and talking to sufferers and their relatives. It was a wonderful study under really difficult circumstances.

“This was one of the classic epidemiological studies, and it’s absolutely fascinating to read about it”

They worked out the epidemiology of the virus and also managed to trace case zero – the village school teacher. He had gone on a hunting trip into the forest just before the outbreak started. Ebola is transmitted by bats, so he must have handled and perhaps eaten one and got infected that way. Then he returned, infected his family and on it went. Once it gets into humans, it transmits from person to person via body secretions. This was one of the classic epidemiological studies, and it’s absolutely fascinating to read about it.

While I was writing my own book on Ebola I went to Freetown in Sierra Leone while the 2014-16 Ebola epidemic was going on, visiting treatment centres and virus testing labs. Obviously this is in no way similar, because I knew perfectly well what protective kit I should be wearing and how to protect myself. But this book certainly struck a chord with me.

There’s something quite sci fi about the idea of going as an epidemiologist into a place where there is a new killer virus on the loose – of confronting, well, alien life, that behaves in strange and mysterious ways.

Yes, but Piot is very down to earth about it. He tells how he’s going out day-to-day in a Land Rover, visiting people in the community. He gives really heartrending descriptions of the villagers who were left mystified. They have all sorts of theories about what happened – but a virus doesn’t enter into it, because they didn’t know about viruses. He is a marvellous storyteller, there’s no doubt about that.

I think we’ve now made it to your fifth book choice. This is Richard Dawkins and Yan Wong’s The Ancestor’s Tale. This is not a book about viruses, per se, but you feel it to be relevant to the study of viruses.

Yes, I do. Richard Dawkins is such a great writer. I could have chosen any of his books, really, because they’re all about evolution, and evolution is extremely important in understanding viruses. They mutate so quickly that new variants can emerge in days. So we really need to know how this can happen. When viruses get into living cells, and reproduce, they produce millions of new viruses. Therefore, within those millions, there are going to be several mutants. If any of those mutants happen to have a selective advantage – perhaps they can spread further, survive longer, infect more easily, or be less deadly – they will take over.

Less deadly?

Yes, it’s not generally advantageous for viruses to kill their host, because then they die with them and the chain of infection is broken. Very rapidly one new mutant with a selection advantage can replace the whole population. So, viruses absolutely depend on evolution for survival. Dawkins called one of his books The Blind Watchmaker and viruses are totally blind but appear very sophisticated. It’s extraordinary.

Dawkins has a wonderful way of expressing himself in writing, and his books have informed all my writing about viruses, because they’ve given me a feeling for evolution. I knew what evolution was of course, but the examples he chooses, and the elegant way he writes… I just find it so insightful.

The Ancestor’s Tale is my favourite, because it’s so clever. Its structure is inspired by Chaucer‘s The Canterbury Tales: it’s a pilgrimage through human existence. The pilgrims are walking backwards through human evolution. Every so often they meet up with our earlier cousins. First they meet other primates starting with chimpanzees, for example, because they are our closest cousin. We separated from them about 6 million years ago. On it goes until eventually they start meeting bacteria. I loved that; I thought it was brilliant.

Yes, and as you say, to understand how viruses work, you need to have a good handle on evolution more generally.

Yes. I come from a medical angle. So, I would have regarded a mutation as an abnormal gene that someone inherited from one of their parents, causing a congenital disease. But with viruses it’s their reason for being. If they can’t evolve, they’ve had it. They’re not going to survive. So they’re doing it all the time, and we are always one step behind.

Are there any circumstances when viruses play a positive role, in the way that bacteria are necessary to the basic functioning of our bodies?

Not really, but there are plenty of viruses that are not harmful. And there are plenty that don’t infect us, but infect other organisms – plants, say. Some viruses that lethally infect bacteria and algae thereby apparently control their populations in the oceans.

We are now using viruses to transfer genes into humans. Because viruses are so good at infecting us, we can take out the harmful genes and replace them with genes that we want to give to somebody – for example a piece of DNA that codes for a foreign protein that scientists want to test as a vaccine. So they infect a person with this altered virus and it will multiply inside them and hopefully induce an immune response to the foreign protein it is carrying.

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There are other viruses – for example, the virus that I worked on, the Epstein-Barr virus – that are so successful that they infect virtually everybody worldwide. I know it sounds incredible, but the majority of people wouldn’t know they have it. It’s not an advantage to have it, but then again, it is not a disadvantage, unless you happen to be one of the few people who do have a problem with it. There are quite a lot of viruses like that, that we’re now discovering. Of course, when virologists were focussed on hunting for viruses that cause specific diseases, they never found these ones because they are mainly silent infections.

I was interested in that point about how, if a virus is too deadly, it’s at an evolutionary disadvantage. Am I right in thinking that some diseases, like chicken pox and mumps, descend from much more deadly viruses?

Yes, certainly. It’s thought that when humans changed from being hunter-gatherers to farmers, beginning around 10,000 years ago, they came into much closer contact with domestic animals, and many of the animal viruses jumped to humans. At first, many were probably quite deadly. But the really vicious viruses in a population killed their hosts and immediately died with them, so it was the less virulent ones that survived. I think smallpox has always been the most lethal, but even it apparently got less deadly over time.

Also, over time, humans developed genetic resistance as the infections killed off the most susceptible. The genetically less susceptible survived, and we are all offspring of those people.

Yes, as Dawkins reminds us, we are all constantly evolving, even today, in response to evolutionary pressures like that.

Yes, but a lot slower than viruses. They’re always one step ahead.

In Viruses: A Very Short Introduction, you quote George Klein to the effect: “The stupidest virus is cleverer than the cleverest virologist.” Where does that leave us? Are we fated to be finally wiped out by a virus that has outsmarted us?

Let me first say that George Klein was a wonderfully clever thinker and a great research virologist. I love that quote. But, no, I have faith in the human race. I think we are genetically diverse enough for there always to be some people who will be able to survive infection with any ‘new’ virus that comes along.

Interview by Cal Flyn

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Dorothy H. Crawford

Dorothy H. Crawford qualified in medicine from St Thomas's Hospital, London and gained a PhD from Bristol University. She is Emeritus Professor of Medical Microbiology at the University of Edinburgh. She was elected a Fellow of the Royal Society of Edinburgh in 2001 and awarded an OBE for services to medicine and higher education in 2005. Her books include The Invisible Enemy: A Natural History of Viruses and Viruses: A Very Short Introduction.

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Dorothy H. Crawford

Dorothy H. Crawford qualified in medicine from St Thomas's Hospital, London and gained a PhD from Bristol University. She is Emeritus Professor of Medical Microbiology at the University of Edinburgh. She was elected a Fellow of the Royal Society of Edinburgh in 2001 and awarded an OBE for services to medicine and higher education in 2005. Her books include The Invisible Enemy: A Natural History of Viruses and Viruses: A Very Short Introduction.