A Journey Through the Virosphere | 91TV
Transcript
- Good evening, ladies and gentlemen, and welcome to the Royal Society. I'm Linda Partridge,
- the Biological Secretary and also Vice President. So before the main event, just a few items of
- housekeeping. Please make sure that your phone is silenced. There are no planned fire evacuations.
- So in the very unlikely event that an alarm goes off, please leave by the fire exit here and the
- assembly point is at the top of the Duke of York steps to the right of the Royal Society. There'll
- be an opportunity to ask questions at the end of the talk, so there'll be roving microphones in the
- room and also for people joining online, we've got Slido so you can submit your questions online in
- writing. So the Croonian medal and lecture is the Royal Society's premier award in the biological
- sciences. The lectureship was conceived by William Croone, who was one of the original fellows of the
- Society, and among the papers that he left on his death in 1684 were plans to endow two lectures,
- one at the Royal Society, the other at the Royal College of Physicians,
- and his widow subsequently produced the means to carry out the scheme, and the lecture series
- began in 1738. The more arithmetically inclined amongst you may have worked out that that was 54
- years after the original idea and I do hope that our implementation has become a little more rapid
- in the time since then. So tonight's lecture is entitled A Journey Through the Virosphere,
- and it will be given by Professor Edward C. Holmes, winner of the Croonian Medal
- and Lecture 2024. So Eddie Holmes is a National Health and Medical Research Council Leadership
- Fellow and Professor of Virology at the University of Sydney. He did his undergraduate degree at the
- University of London and subsequently PhD from the University of Cambridge, and his research focuses
- on understanding the nature of global virus diversity, so the virosphere, and the major
- mechanisms of virus evolution, with a special emphasis on revealing ecology, evolution, and
- emergence of RNA viruses, including SARS-CoV-2. In 2003, he was awarded the Scientific Medal by the
- Zoological Society of London. He was elected a fellow of the Academy of Sciences in 2015,
- and a fellow of the Royal Society in 2017, and in 2021, he received the Prime Minister's Prize for
- Science in Australia. I'm delighted to ask Eddie to come and give the 2024 Croonian lecture.
- Thank you, Linda. I've actually got some water hidden here somewhere. It's obviously a great
- honour to be giving this lecture that's so well esteemed and has such antiquity, and I really
- thank the Royal Society for this privilege. Also thank you for coming. I know some of you
- have come a very long way. This is supposedly spring in Britain, but it's great, I'm really
- happy you've come and I'm delighted you're here, so I'll try and make your journey worthwhile. As
- Linda mentioned already, what my work is on is this thing called the virosphere,
- which is this sort of global diversity of viruses. The plan this evening, briefly,
- is to give you an insight into what the virosphere is, how it's structured, how diverse is, how big
- it is, and how it's evolved. So I'm going to give a guided tour of this massive universe
- of viruses that surrounds us in our everyday life. Before I do that, I actually thought I'd
- start the lecture off with a little bit of a preamble, just to introduce a few key themes,
- and that preamble is about one particular virus that's been hugely important in human history
- and that's smallpox. Smallpox is the disease. The virus that causes smallpox is called the variola
- virus. Now, as every school kid knows, it's textbook, vaccination started, for any disease,
- started in 1798 by a doctor from Gloucestershire called Edward Jenner. He wasn't the first person.
- He didn't invent vaccination. It had been used in other cultures before, but Jenner was the first
- person to use it in the West. As every school kid knows, the story is that Jenner found a milkmaid.
- Her name was Sarah Nelmes, who had these lesions on her hand that were caused by cowpox. She had
- got that from milking a cow that had these lesions too. The cow had cowpox. Jenner realised then
- that cowpox, he found that could give protection against smallpox, hence vaccination. So he started
- a vaccination campaign in 1798. This is a very famous picture from early on. This is Jenner here.
- It talks about cowpox. So here he's vaccinating people. You can see little cows coming out of
- them. This is the first kind of anti-vax picture ever. So right from the get-go, people worried
- about vaccination. Then in a triumph of medicine, in 1980, following a global eradication campaign,
- smallpox was declared eradicated. This is still the only human disease known to be eradicated.
- It's the only human one. So that's well known. It's textbook stuff. The question is: smallpox,
- where does it come from? How old is it? So clearly it was around in 1798 but how much further can we
- push the evolution of smallpox back? So in some work with Hendrik Poinar from Canada,
- I'll show him a bit later on, we've been trying to work out where smallpox comes from. How old
- is it and what's its history? The first thing we did was try and find some early smallpox samples.
- Hendrik found some archaeologists who were working in Lithuania. This is Lithuania is down there,
- and the capital of Lithuania, you may know is Vilnius. In Vilnius, there's a church called the
- Dominican Church of the Holy Spirit. That's the church. In that church, there's a crypt. In that
- crypt, there are coffins, and in those coffins, there are mummies, and these mummies are people
- who died of smallpox. This is actually a mummy. Sorry, you're going to see quite a few of these
- things tonight. So brace yourself. This is a mummy of a two year old child and there are pox
- like lesions in this mummy. Hendrik was able to take to sample this mummy and get the sequence,
- the complete genome of the variola virus from these mummies. These mummies date between 1643 to
- 1650. So when you've got that genome sequence, you can start to do some evolutionary work and that's
- kind of what we did next. So again, this is the variola virus, the cause of smallpox. So first,
- the main thing you can do is you can do what's called an evolutionary tree. Now for those of you
- that aren't used to evolutionary trees or seeing them, they're just like family trees pedigrees,
- but they're kind of stretched in time. So this is a tree of smallpox, variola virus strains.
- So these ones here from Botswana, they're closely related, they're close to ones from South Africa,
- they're a bit further away from ones from the Congo, etcetera. So this tree's a a bit special,
- as well as having the relationships, who's related to who, it also has a time scale because this is
- called a molecular clock tree. So because viruses can evolve at a fairly constant rate, you can use
- that property to date when they evolved. So here, we managed to put a time scale on the evolution of
- this virus and that dotted line, that marks 1798. So that's the date when Jenner starts vaccination,
- and there are two things I want you to see from this tree. First, the strain, the sequence we
- got from that mummy from Vilnius is up there. So it's more diverged, it's basal to all the other
- more recent strains of variola virus. There it is. If you work out using the molecular clock,
- they share an ancestor actually not too much older, about 1600 or so. What's also interesting,
- you can see that the vaccination started there, and most of the diversity of the virus we found
- arose after the vaccination. There's actually two different strains of smallpox, a major and a
- minor, and they appear to have diversified pretty close to when vaccination happened. So you've got
- quite a recent evolution. So the next question is, okay, so that's the evolution, what about
- the vaccine itself? Can we put the vaccine strain that was used by Jenner during the 19th century by
- the people on this tree? So what Henrik then did is he looked to see if he could find some early
- vaccination kits. So he went to a US Civil War Museum and they actually have in their possession
- some of these very early vaccination kits. There's one here called the Automatic Vaccinator. Great
- name. Now these were not needles back then, what they used to do was take a thing called a lancet,
- that's that little tool there, and they would make a little cut and then rub the vaccine in rather
- than using a needle. So that's what you're seeing there. So what Henrik was able to do was take
- these kits and then wash them in solution, and then the residue from that washing contained the
- virus in the vaccine. So we managed to sequence the virus that was used in these early vaccination
- kits. What you then see, you can place it on that evolutionary tree, what you see though, it's not
- actually one, the virus is not - as we think it's cowpox. It's not one of these viruses here. In
- fact, it's a kind of bigger tree to see where it falls. This is a tree of all the mammalian
- pox virus, and it's a bit complicated but just to orientate yourself. This is the variola cluster.
- So this tree here is all that there. There's a Lithuanian one. The vaccine strain that they use
- in the US civil war, it's over there, and it's next to a thing called horsepox. You
- can see the word cowpox all over the place and there's vaccinia there as well. Now,
- what does all this mean? Well, it turns out all these strains here are the cowpox strains. So the
- vaccine they used in the mid 19th century is, in fact, a thing they think called horsepox,
- not cowpox. How does this make sense? Well, it turns out though it's called cowpox, or vaccinia,
- because vaccinia is from the Latin for cow, which is vacca. That's where vaccine comes from. These
- viruses are not from cows or horses. In fact, we have no idea what their natural reservoir is. They
- definitely infected cows, they definitely infected horses, but they are not the natural reservoir. In
- fact, we have no idea where these viruses come from at all. We have no idea what the natural
- host of these pox viruses is. We know that at some point around cows, at some point in horses,
- but we don't really know where they come from. So in particular, look at the variola cluster. The
- closest ones, the human viral strains are cowpox, and taterapox, actually from a gerbil. Okay,
- so the first point I want to show you in my talk is there's a huge diversity of viruses out there
- in nature, and we don't know much about them. The virosphere even as a little tree here is pretty
- large. So this is 1860s vaccination kits. Can we go back even further? Can we actually look at
- the virus that Jenner used? Was that the same? Was that the same horsepox thing? How is this
- possible? So it turns out that, again, the story is that Jenner got the lesions from a milkmaid
- who'd milked a cow with cowpox. Now we actually know who that cow is, and that cow is called
- Blossom. Blossom is a kind of celebrity. This is like Instagram of the late 18th century. Someone
- from the Jenner family painted Blossom and there she is. This is the cow that had the lesions.
- Amazingly, Blossom's hide is still around today, and it's actually in the library of St George's
- Hospital in Tooting. So you go to the river, go in the library, they claim to have. It kind of looks
- a bit like the same kind of thing. They claim to have this cowhide that's Blossom in their library.
- Now, Henrik took this picture. You see, it's not a very good picture, there's a reflection because
- it's behind a glass screen, and that glass screen is there to protect it from anything noxious in
- the environment that might contaminate it. That's my one gag for the evening. Anyway,
- so what Hendrik done. Hendrik thinks he looks like this, but this is Hendrik. Very kindly, actually,
- by St George's, they've allowed him to sample this hide and we've got other bits of nose and ear,
- and he sequenced them using metagenomics, and they do contain a poxvirus. Now,
- we haven't yet got it perfected, the technique, to work out exactly what it is,
- but they do have some sort of poxvirus there. So maybe this will come in the future. I've
- told you that long preamble for three reasons. One, it's a really good story, actually. It's a
- great bit of medical history. Two, it's about the diversity of viruses in nature. Third,
- the main reason, is that what I think has happened, I'm going to argue the rest of
- my talk is that, because of things like smallpox that we worked on early on in history of virology,
- our whole view of viruses is biased. We have a bias that by looking at viruses that infect
- humans or things that humans care about, and a bias in thinking about viruses as pathogens only
- causing disease. I will tell you for the rest of my talk is that's not true. There are many,
- many, many more viruses that have nothing to do with humans at all and I think most of them don't
- cause disease. So I think our view of viruses is biased, and I think it's because the way virology
- was founded, that bias set in. Virology was born at the end of the 19th century, start of the 20th
- century, and the first virus ever described was Tobacco Mosaic Virus, because tobacco was a big
- cash crop at the time. These are the people, these stamps here on pictures, these are the
- three people that were involved in that discovery. I won't go into any detail, but briefly, what they
- did was take lesions from a Tobacco Mosaic Lesion from a tobacco plant from the leaf, they took
- the sap out of that, and they passed it through smaller and smaller filters that would normally
- capture bacteria, and it was still infectious after doing that. So they knew it was smaller than
- the bacterium, and they called it a filterable agent and that became the virus. So TMV was the
- first and shortly after, there were a few other viruses, but they were really mainly pathogens,
- because they caused a disease and things, viruses, that humans cared about. I think that's a bias. I
- think that's kind of thwarted, that's kind of influenced the way we think about viruses in a
- kind of distorted way. I think what I'm going to try and show you now is that this view is missing
- the real virosphere. Most viruses are not like that, and I think this virosphere that's out there
- beyond, it's absolutely enormous. Now just how big it is, I can give you a few pictures. Some of
- these are not very good. So a few years ago, I was asked to try and work out how many viruses there
- were. So I kind of like guessed. The number I came up with, and this really is a guess, was for
- carriers, I guessed 87 million viruses. Now that number, I didn't really pull it out of thin air,
- but the idea was if there are 8.7 million new carriers as estimated, maybe each of them has
- ten viruses. It kind of varies a bit. So there you get 87 million. Of course, there's a huge
- error bar on that. So then that's the size of that virosphere. A few years ago, the total number of
- viruses formally classified was about 4500. It now may be 12,000 or 13,000. So that's the size of the
- classified. Of the human viruses, that bit there, we have about 219 there, maybe 250 or so. Another
- way of looking at it is to look at the viruses that have been characterised and what animals
- they're from. This is the chordates, and you can see most of the chordate viruses are from mammals.
- That's not because mammals have most viruses or there are most mammals. It's just that those
- are the ones we preferentially worked on because we are mammals and we eat mammals,
- and mammals are our pets. A few bird viruses. There are many to do with avian flu. A few fish,
- but lots of other taxa, nothing, and that's simply biased. That's simply not looking. The good
- news is now with genomics, and I'll discuss this throughout my talk, with developments in genomics,
- we're beginning to see more of that virus. This is just showing you the number of papers
- on viromes biodiversity studies in the last 20 years. These are basically, these blocks here,
- these are innovations in genome sequencing. As that's got better, the number of viruses being
- described is just massively increasing and that's changing our view of the virosphere and what we
- think viruses are. I'm going to discuss this kind of movement now. So today, this is the kind of
- questions you're going to get to. So to summarise very briefly and look at the scale of the
- virosphere and how we discover viruses, the origin and antiquity of particular viruses,
- looking at viruses within individual ecosystems, and finally, the bit about how humans get disease,
- how viruses emerge in humans, and that's all going to be about the human-animal interface because
- we get viruses from other animals. I'm going to show you how that happens briefly. So how do we
- discover the virosphere and how big is it? So the way we do that, I've already mentioned it already,
- is using metagenomics. I won't go into any detail. It's not the right place for it. But all that
- really means is, the meta means all, and these metatranscriptomics. So you can either sequence
- a sample, you can sequence all the DNA or all the RNA. So here's your sample. It can be Blossom's
- hide or it can be an environmental surface like this or a person's blood. You can sequence the RNA
- or the DNA. We do the RNA. So you go through some prep steps, then you sequence it. Then you have
- lots of little bits of RNA, and you use computers to work out which is virus, which is host, which
- is bacteria, and then you can use phylogenetics and other tools. So very, very standard approach.
- This approach is transforming our understanding of the virosphere. A really good example is on
- bat viruses. So when bats were discovered to be the reservoir for SAR-1. SARS-1 emerged in 2002,
- in southern China. In 2005, bats were found to be the reservoir for that virus. After that time,
- there's been a huge increase in people trying to do metagenomics on bats to see what viruses
- they have, and you can see that by looking at the number of papers published on - viruses come in
- two flavours, RNA and DNA, basically. So you can see the number of papers published on RNA viruses
- and DNA viruses, and basically these are bat viruses and they're growing dramatically. So these
- are metagenomics, people are now discovering more and more of these bat viruses. Interestingly, the
- biggest pie slice in any of these two DNA/RNA pies is that one. I'm colour-blind, whatever colour
- that is there. That's the coronaviruses, like SARS-1 and SARS-2 are very, very common in bats.
- So you can see bats as one example. Big increase in numbers because of metagenomics. Now while I'm
- here, I want to digress for one slide about bats because so much is talked about bats, and bats
- are hugely important animals in our ecosystem. They pollinate and they get rid of insects,
- and there's lots of myths about bats and viruses that are out there and I'll sort of counter two of
- them now. Myth one is that bats don't get sick. Now, bats are not magic. They've had disease
- outbreaks like every other species had, very nasty fungi, they've also had viral diseases. Bats do
- die of viruses. In particular, we have evidence - this story, these pictures here, this is a grey
- headed flying fox, a fruit bat from Australia. I'll show you that in a second. It's got some
- very nasty skin lesions. I'm not a histologist, but this apparently, this cell picture here is
- of a lymphoma. This is a grey headed flying fox with lymphoma, and we can show that that lymphoma
- is caused by retrovirus. So bats do get viral diseases. I actually have a little video of a bat,
- this is a grey headed flying fox, those of you that have been to Sydney, these are very,
- very common in Australia. They're almost suburban. They can fly hundreds of kilometres at night.
- They're lovely animals, but they do get sick, and people pick these things up with their hands and
- they bring them into the local vets. This video, this bat has a neurological disorder. This is
- not normal bat behaviour. We're not entirely sure what it is. We think it might be an astrovirus. So
- bats do get sick. The second myth that you hear is that bats carry lots and lots of viruses. Bats do
- carry quite a few viruses, but in all my years of looking at animals, they carry, I think, no more
- than rodents or insectivores. I mean, they're quite rich in viruses, but I don't see them
- as being these mega carriers. In some cases, they have no virus at all. In one particular case we've
- just done recently is another flying fox. This is called the Christmas Island Flying Fox. There
- it is there. This is the Indian Ocean, this is Australia. This little spot here, this is actually
- an Australian territory called Christmas. It's not a very Christmassy place at all. It's kind of
- tropical. On that island, there's a population of about 2000 of these left. They're very endangered,
- so there's a big conservation effort going on. In this particular flying fox population, we've done
- lots and lots of sampling and found no viruses at all in them. So they're completely refractory.
- They're isolated. Actually, I mainly showed you this picture because I get to show you the cutest
- video ever. Ready? So this is actually the size of your hand. It's actually in someone's hand. It's
- tiny. It's an amazing animal. Okay, sorry, that's my bat digression. I could watch it all day.
- That's my bat digression. So metagenomics then is transforming our understanding of the virosphere.
- The first real indication that the virosphere was far bigger than we ever thought was actually not
- on bats, it was actually on invertebrates, and this is a very recent thing actually. In 2015,
- I did a study on some particular viruses that are called orthomyxoviruses. Orthomyxoviruses are the
- family of viruses that include influenza. This is a tree I drew from a paper in 2015. This is flu
- A in the coloured box. This is flu B. There's a couple of other animal groups here. So vertebrate
- viruses we thought. Then what happened is my colleague and friend, Yong-Zhen Zhang, you may
- have seen him in the news recently. I submitted these slides before the recent thing happened.
- He's doing okay. I emailed him this morning actually, we had a chat. I can discuss it at the
- end if you want to discuss how he's doing there. There's Zhang there. He decided, let's look at a
- really big diversity of invertebrates to see what viruses they have. This is Dr Lin from the Wenju
- CDC. I think this is Forbidden City here, having a photograph. So Zhang thought, let's go and sample
- lots and lots of invertebrates, they never looked at it before, to see what viruses they have. This
- was led by my postdoc, Mang Shi, and he looked at 220 species from nine phyla. So normally
- prior to this, the only invertebrates people looked at the viruses were basically ticks and
- mosquitoes and Drosophila. Drosophila, the great workhorse animal, and ticks, mosquitoes because
- they're vectors. Nothing else had been looked at. What Mang managed to do is look at things like,
- he had a picture, you've got cnidaria like coral, jellyfish, nematodes, crustaceans,
- myriapods, lots and lots of them. What you find is they're absolutely full of virus. Now I can't
- tell whether they're causing disease because it's hard to know what a sick nematode looks
- like compared to a healthy one, but these animals carried lots and lots of viruses. You can see that
- over here, these are just different trees of RNA viruses, bits of RNA virus tree. All you can see
- is the colours. The ones in grey are what we knew before the study. The ones in red are what
- we discovered in this one paper. So a massive increase in the diversity of viruses from one
- study. So we've missed all this virosphere, and they actually often, in the insect, in the animals
- themselves, they often have very high abundance. So you go back to this orthomyxovirus tree from
- being like a vertebrate virus in a tree, now it's much bigger and it's surrounded by invertebrate
- viruses and things from the environment. In fact, the real tree is much, much bigger. I had
- to shorten it to get on this slide. So we've got a complete change in our perspective of viruses by
- doing these samplings of other animals. So that was invertebrates. The next thing we do is look
- at chordates, vertebrates and their relatives, and the same thing. So again, Mang led this work,
- and up until this paper, most people had looked at mammals when they thought about chordates. So
- here are the different RNA virus trees. The red, they're colour coded by vertebrate class, the red
- are the mammals. What Mang did particularly was look at fish. So all that blue, those are the
- viruses that Mang discovered. So suddenly, groups that we thought were mammalian, we now found are
- in other vertebrates like fish. For example, the filoviruses like Ebola, everyone thought that's a
- classic kind of bat virus. In fact, we have it in fish as well. So again, it's changed our view of
- the virosphere. Some of the animals we looked at were really interesting. My favourite is this one.
- This actually exists. Who knew? This is the mini pizza batfish. Before you try and eat it, this
- actually had a whole bunch of hantaviruses in it, it turned out. It's on the tree somewhere there,
- so pretty cool. I'll give you one example. One really nice example of this transformation of our
- thinking is the kind of textbook virus, almost, that's flu. So the classic view of influenza,
- which everyone knows, is that it's a bird virus, an aquatic bird virus. So waders and shorebirds
- have the virus. It then goes from them to poultry, or to pigs, and then from poultry,
- chickens and turkeys, or pigs, into humans and some other animals too, and now we have cattle
- in the US as well in this picture. That's the kind of classic view of flu. We now have by looking at
- other vertebrates, a very different view of the tree of flu. It actually looks like this. So this
- is influenza A virus, that one I just showed you. That's a human. There's a pig. There's the birds.
- There's flu B, but around it now, we have lots of viruses in other vertebrates we never thought. So
- here, we've got salamanders, eels, salmon, toads, hagfish, that's a jawless vertebrate.
- My favourite of all tunicates, we've actually just found, this is unpublished. So these are
- sea squirts. Tunicates are the closest sister group to the vertebrates, the most vertebrate
- like invertebrate. These are sampled from Sydney Harbour. They have influenza. So sea squirt flu.
- So a completely different picture of the group for this virus, that looks very ancient. So there's a
- huge virosphere out there. You can see it in these particular groups. But how diverse really is it,
- and how old is it? So what you can then do is you can do, if you want,
- you can do phylogenies of all the viruses. Here's a tree of all the RNA viruses. It's a little bit
- meaningless. This is a formal classification. You can forget the names here. All I want you
- to see is the scale bar. Now, this tree is done using the most conserved gene of RNA viruses and
- that gene is the gene that encodes the RNA. RNA viruses, RNA makes RNA. So this is the gene that
- encodes the RNA polymerase otherwise known as RNA polymerase. So it's the most conserved gene. That
- is the scale but that's 80 per cent divergence, right? So these things are massively, massively
- divergent. In fact, you should not align these and you should not do trees. I've done it here to show
- you, but you really cannot align them. It's so, so divergent. You've got to put in perspective.
- I've done a k very slightly dodgy comparison. This is a tree I got from the literature. This
- is a tree of all cellular life using analogous ribosomal proteins. So here, we've got bacteria,
- here, we've got eukaryotes, and archaea. This is a tree of all cellular life, and this tree here is
- about 20 per cent bigger than this. So there's more diversity of known viruses than the rest
- of all the tree of life. But there's a problem, because this is the known virosphere, and it's
- based just on looking for similar sequences. The problem is as sequences get more and more
- divergent, you can't detect them. There's so many sequences, you can't see the virus because its
- sequences are so different. So this circle is a kind of boundary, I think, of where we can detect
- viruses using similar sequences. Out here, there could be viruses we just can't see because they're
- so divergent in sequence. So how do we explore this hidden virosphere? What we're trying to do,
- as are others, are rather than using sequence, we're using protein structure, because structures
- are more conserved than sequence. So what we're looking at is that most conserved gene, the RNA
- polymerase, this is one here from one virus, trying to look for that structure in sequence
- data to try to identify viruses. The idea is if we can do that, we can detect some of this blue bit
- of the circle, this hidden virus that we can see for the first time. Now the way we do it, and this
- is the most technical slide of my entire talk, is using AI. This is the way these days,
- right? This was work done by, again, this is Mang. This is his European helper. This work is
- done mainly with Alibaba Corporation in China who have huge computing resources. Briefly,
- I won't go into detail. Basically, we have two approaches to do this. One, what we call sequence
- based clustering. It's kind of just looking for similar sequences but in a building structure. The
- second way is a straight AI way. So what you do is you tell the program, you give it every known RNA
- polymerase structure, it's trained to recognise those structures, then you give it sequences, you
- don't know what they are, and it recognises the structure in those sequences. In doing that, so
- using all the data available on public databases and plus stuff we sequenced ourselves, we
- discovered 161,000 new viruses in doing that, that fell into 180 different classes. Once we sequenced
- ourselves, we only found them in an RNA sequence and a DNA sequence suggesting really RNA viruses.
- Sorry, it's a technical slide. Very briefly, these are the environments they're from. Lots
- of these things are in sediment here. It's called sludge, basically soil sediment, there's loads of
- virus. Also, lots were in aquatic systems up there. This is just showing you that we're not
- anywhere near to bottoming out in discovering new viruses. So this is the number of samples against
- new viruses found. It's still going up. So there's lots and lots more to discover. To visualise this,
- look at this figure here. This is my plot of the viral universe, the virosphere. I'm colour-blind,
- it's like a colour-blind shot. The grey circle, they are the known RNA viruses. So
- if I go back some slides. That grey is that, okay? That's the grey. The blue dots are the
- clusters that were discovered using the sequence similarity method. The orange dots, the outer
- edge of the virosphere, looks like the galaxy, that's discovered using AI. That's as far as you
- can stretch into finding diverse viruses by our approach. Another way of looking at it is looking
- at phylogenies. Very complicated. Don't worry. All you can see, these are the different groups
- we found. The green was known. The yellow is new. These whole phyla that you can now see for the
- first time, this sea of yellow is a completely new phyla, or whatever they are. Who knows? I'm
- going to now focus on one particular group in in detail to show you how this new stuff works,
- and that's this one here. It says nido, and these are the nidoviruses. What, you may say,
- are they? Well, this is the order of viruses that contains a number of viral families, but two are
- very important for disease. The coronaviruses like SARS-1 and SARS-2 and the arteriviruses. Now,
- you wouldn't have heard of those, but I'll show you a little video in a second of what they are.
- This is a phylogeny of coronaviruses. So there's SARS-1, and in the big picture, there's SARS-2.
- These are other coronaviruses, and these are basically mammalian, but what we've discovered
- are there's a whole bunch of other coronaviruses found particularly in fish. Again, coronaviruses
- have an aquatic ancestry. Even more interesting, see this little thing here, it says Kanakana
- letovirus virus. That's not from a fish. That's from a New Zealand lamprey. So that's a jawless
- vertebrate and they have a coronavirus. So you can think, this probably, this node here is probably
- the age of the vertebrates. The other group of the arteriviruses, there are also nidoviruses,
- you wouldn't have heard of those, but in Australia we have a lot of very common animals we have in
- our backyards, opossums, and they get a disease. Amazingly, it's called wobbly possum disease,
- that's caused by an arterivirus. Let me play a video here. This is from New Zealand, and the
- person who posts this on YouTube was saying, 'This possum's drunk.' It's not drunk. It's actually got
- encephalitis, and that encephalitis is due to an arterivirus causing this wobbly possum disease.
- So we sequenced this virus and it's here. If you look at the tree of the arteriviruses,
- it really closely matches the host tree. These are mammals. These are marsupials, reptiles,
- amphibians and fish. So it absolutely parallels the host trees. So that tells you that that group
- and this group are probably, at least 500 million years old. So this is one family, one group, and
- one order, and they are ancient things. This age, this antiquity of each individual group is really
- now, you're seeing it in virtually everything you look at, and you particularly find these viruses
- in ancient aquatic systems. So looking at aquatic systems transformed our view of the virosphere.
- Another really good example mentioned already are the influenza virus. It's already showing
- you here. We've got sea squirts in flu. If you expand that, you find even more divergent aquatic
- influenza-like viruses. This is work done by my postdoc, Mary Petrone, and what she's
- done is sampled cnidaria, these are a phyla of invertebrates that contain corals and jellyfish
- and hydra, and she sampled these, and she has found relatives of influenza in these cnidaria.
- This is a very difficult tree. This is the order that they're in. These are terrible names, the
- articulavirales, and this order of viruses that contains influenza viruses has cnidarians that
- have viruses in them too. So here, this is her tree, to orientate yourself, this is the influenza
- viruses. So this is all this. You can see out here, there's a symbol for hydra. So there's
- one here. In fact, many of these ancient aquatic animals have influenza-like viruses. So this order
- is probably at least 600 million years old. The same is true of many other viral families. The
- flavivirus is very common, like dengue, yellow fever. We've also found them in cnidaria as
- well. These are ancient, ancient things. What Mary's doing now, has just done, is trying to
- look at some even more ancient organisms, and that cyanobacteria. So in Australia,
- we have a fantastic place called Shark Bay on the West Coast. Have you ever been there? It's a
- beautiful World Heritage site. In Shark Bay, there are things called stromatolites. These are like
- housing estates for cyanobacteria. They date to about, the fossils can go back 2.8 billion years,
- these are ancient living things. Mary has managed to sample - with approval, I should say - managed
- to sample some stromatolites from Shark Bay, and it's actually being sequenced at the moment, so
- hopefully we'll find some stromatolites viruses. Now, I'll change tack briefly about rather than
- looking at viruses, families as a whole, let's look at ecosystems. So one particular place. How
- do viruses interact in one environment? Again, I'm going to stick with aquatic environments because
- I think they're really cool to work on, and I'm actually going to talk about fish. I'll give you
- two contrasting fish ecosystems where the virus evolution has worked a bit differently. The first,
- the very famous one, a lake ecosystem, and that's Lake Tanganyika. So the evolutionary biologist
- will notice very, very well, these are the Rift Valley lakes in East Africa, the largest of which
- is Lake Tanganyika. In that lake, there's been an amazing radiation of these cichlid fish. So
- 10 million years ago, the ancestor of these fish gets into the lake and then there's an amazing
- radiation of these fish afterwards into 240 species, 11 tribes, one ancestor in one lake,
- with huge variation in body form, sizes, shapes, colours. It's a classic Darwinian radiation. Now,
- my colleagues, Fabrizio Ronco and Walter Salzberg from Basel, have done a lot of
- work on looking at these fish, and they've done a lot of RNA sequencing. We looked at their RNA
- sequence data and to their amazement, these fish were absolutely full of viruses. No sign
- of disease, I should say. Absolutely full of viruses. These are very technical slides
- again. So these cichlid fish in Lake Tanganyika were swimming with viruses. So here are the
- different fish, different tribes, and here's a map showing you the different viruses they have. Not
- particularly interesting. This is actually more interesting. This is the tissue they're found in.
- It says LPJ. That stands for lower pharyngeal jaw. So fish viruses are passed on through the water.
- So they're excreted at the back end and as the fish swim along and open their mouths, they come
- in. So this jaw region is the first place they're exposed to the fish and it's the bit that contains
- the most virus. So lots of viruses in these fish, but the key thing, the most important thing of all
- is these viruses were really commonly shared between the different fish species. There was
- lots and lots of host jumping emergence, because these fish are extremely closely related, they've
- all radiated the last 10 million years. The most divergent fish pair are the same distance as human
- and chimp, which are very similar. That's the most divergent. Most are much more similar. So they're
- so similar genetically, there's no barriers for the viruses to jump. They have the same cells,
- the same immune systems. The virus can easily find a receptive cell in a different host species.
- So you have lots and lots of host jumping. So compare that to another fish ecosystem. That's an
- Australian one and that's the Great Barrier Reef. We have this amazing ecosystem in Australia. I
- live about here, not here sadly, I live up here. So in Queensland, this amazing reef ecosystem
- that's home to 1200 fish species, and about a third of marine fish live in these tropical reefs.
- The key thing for us is they live at very high population densities. So in a 3.5 metre square
- area, you can get 25 different species of 150 individual fish. So we thought, okay, there'd
- be so many fish there in one little place that the virus would be jumping, they would be banging into
- each other, the virus would be jumping very, very frequently. So what we did, this was work
- with David Bellwood from James Cook University, we went to two islands, Orpheus Island down the
- southern reef and Lizard Island in the northern reef. So this is Lizard Island. It's a tough job,
- but someone's got to do it. Sadly, now, because of coral bleaching, I don't think Lizard Island quite
- looks like that anymore. So this is actually this reef that we sampled. There's lots and lots of
- fish there in one ecosystem. So what we did was go to these two islands and just take 100 metre
- square transect and sample all the fish in those areas, and doing that, we found 258 viruses. Some
- of the fish we looked at, the cool thing about these fish, they were often what are called crypto
- benthic fish. They're very, very small and very short lived. Very short lifespan. It's a bit like
- the cast of Finding Nemo. My favourite one is actually this one here. The zebra dwarf goby,
- or goby, however you say it. This is actually the size of my thumbnail and they live for
- about 60 days. Even these tiny little fish that have very short lifespans are full of virus.
- So what we found was, again, lots and lots of virus, but critically, no host jumping. So even
- though we've got a very small sampling area, the viruses, they're not being passed between species,
- in complete contrast to what you see in Lake Tanganyika. So why is this? Because these fish
- species diversified long ago, 40-plus million years ago, and they only came together on the
- reef when the sea levels were reduced in the last 10,000. So the Great Barrier Reef is
- actually quite a recent innovation but the fish are much older. So by the time they come together,
- they'd built up a much bigger genetic boundary for the viruses to jump. Cells are different,
- immune system different. They just don't move between them. It's a very stark contrast to
- Lake Tanganyika. What's also very interesting is that we have these small fish and bigger fish,
- and these cryptic benthic fishes actually had more viruses than the larger, longer lived ones. Now,
- why? I don't know. I wonder whether it's because if you live such a short lifespan, there's no need
- to invest in immunity, right? So you just kind of carry viruses very frequently. That's a theory.
- So I mainly work on aquatics, I'm getting towards the end, work on aquatic systems. Just to give you
- two other ones that we work on. One is aquatic mammals, particularly whales. So whales wash up
- on beaches in Australia fairly regularly, and because of that, we're interested in, is that
- beaching due to disease? So we sample them, but they're diseased whales. We've also tried to look
- at healthy whales. The way we've done that is to sample whale blow, which is basically snot. So
- when these whales blow, they get this mucus matter that's kind of projected out. So we try to sample
- that using drones. I'll show you a little video now. This is Sydney Harbour. This is Sydney. Those
- who know Sydney. This is North Head. That's south. This is the city here. So just watch a little
- video, and I think there will be sound too. So you take it back. So that in theory, is whale snot. So
- you take it back and then you sequence it. We did that, and sadly, all the viruses we got,
- I think were seawater viruses rather than whale viruses, but anyway, it was a fun thing to do. So
- that's one thing we do. The other thing I'm just doing now, and I'm going to say aquatic system,
- but it's a little bit of a misnomer, is looking at crocodilians. In Australia now, we have a vast
- population size of saltwater crocodiles. Hunting was banned for a while. Now hunting's not banned.
- So don't swim in Northern Territory River, whatever you do. Now, there's a big increase
- in the numbers of saltwater crocodiles, and we're sampling them. So my student has done this. You
- can actually take a throat swab from saltwater crocodile. You anaesthetise it, and you put a tube
- in your arm and you go into the crocodile's mouth and you pull it out. My student's called Lauren
- Lim, and I told her she shouldn't come back Lauren limbless. She didn't like that joke very much. By
- the way, this is a dead crocodile, and we don't kill. It wasn't us. Amazing animal. Okay, so the
- last little bit here very quickly. I've shown you how big the virosphere is. It's actually enormous,
- right? The next question is, how do these viruses in animals end up in humans? Occasionally, that's
- going to cause a pandemic like we've just been through. So how does that happen? It's because
- this human animal interface is the bit where animals and humans interact, and I'm going to talk
- about one particular bit of the interface that I think is particularly troublesome, and that is
- the farming of wildlife for game and for fur. I think that's a particularly risky thing. So when
- COVID started, some colleagues in China decided, let's go and sample some of the animals that were
- being sold in these live animal markets, and the markets are closed in China, but the wildlife
- breeding farms are still open, and it's not just true of China, it's in many countries. So I'm not
- picking on China here at all. So what they did was go, and very famously these animal markets,
- there were menu boards with live animals that they sold. So what we did was go and
- sample in these breeding farms, these animals that were then sold on in markets. So here,
- we've got hedgehogs. That's a porcupine. That's a civet, raccoon dogs, badgers. That's a marmot, a
- bamboo rat. That's a pangolin. This is work done with Shuzo Siu. Shuzo sampled about 2000 animals
- from five mammalian orders, In that, he found 21 viruses that we think were risky because they
- were being found in different mammalian orders. So they were jumping species boundaries, and that's
- your number one worry about a virus that's going to emerge, if it's jumping already, including,
- for example, with a bat, coronavirus in a civet, and an avian flu in an Asian badger. So this is
- a bit abstract. I'm trying to bring it home to you, and I apologise for this, I'm going
- show you a few videos now, okay? So this is an Asian badger in one of these wildlife farms,
- and if you watch his nose, this animal has avian flu, H9N2. These are raccoon dogs,
- and I think there's going to be sound as well, if you listen very carefully. She's got a cough.
- So that's got a respiratory disease. We're not entirely sure what that is. They're being bred for
- their fur. Lovely animal. This one is a bit more confrontational, so I apologise. This is another
- raccoon dog, a younger one, and they've suffered a very nasty kind of gastric haemorrhaging disease.
- We think it's canine coronavirus caused this. What worries me most is the person is handling
- it with their hands. So this is to me where pandemics start. Now what we've just done,
- this is unpublished, and again, this is Shuzo, it's amazing work, he's gone and sampled more fur
- farms in China, but this time he's focused on, our first paper looked at animals that had no disease,
- we thought on average. This time he's looked only at diseased animals. So this is China. Again,
- it's not just China that fur farms. Most fur farming takes place in northeastern China,
- Shandong. Here are the animals that are fur farmed. It's a huge kind of zoo of animals they
- fur farm. There are a few species far more than others, but many species are fur farmed. Sorry,
- I apologise. He saw about 461 animals that were sick. They had disease. In fact, they
- died of disease. He found 123 viruses, 39 were risky because they were jumping between mammalian
- orders, seven new coronaviruses, a whole bunch of avian flu viruses, including in things like guinea
- pigs. These figures are showing you the animals and the viruses they have in two different ways.
- This is how the viruses are connected. Here are guinea pigs. It turns out guinea pigs, which you
- may think are great pets, actually have a huge number of viruses when they're farmed for fur,
- which is quite concerning. Raccoon dogs and mink had the most number of these viruses
- jumping between species, which is kind of concerning. The one I put in red is the one
- I'm particularly worried about, which I'm just going to show you now, this is unpublished.
- We had two mink that had died of pneumonia and they had a BAT-HKU-5 coronavirus in them. This
- bat coronavirus we've known for a while. It had not been known in any other species before, and
- now we have it in fur farm mink that have died of pneumonia, and worse, virologists in the audience,
- Stewart, this virus uses ACE2 receptor. So that is a concern. So I think this industry is, to me,
- the most obvious place where the next pandemic will come from. I'm going to end with this. You've
- heard a lot of virology in this talk. At the moment, it's a difficult time to be virologist
- because there's a lot of negative press going on about virology, and there's a lot of tension and
- bad feeling and harassment going on. I just wanted to show you that virology has actually done a huge
- amount of work in biology, not just for obvious things like vaccines and antivirals, but for tools
- that are used in molecular biology, for basic understanding of biology. The definition of DNA,
- the form of how lives are inherited, of reverse transcriptase of mutations, they come from phage,
- it's virus work. So virology has actually played a hugely important place in biology. So rather than
- kind of vilifying virologists, it'd be kind of good to go and give them a hug, actually,
- because they've actually done a huge - not too close - because they've done a huge amount of work
- on our understanding of how life works. Last slide is just to thank. Obviously, I'm at the
- end. This is 35 years' worth, what you're seeing is a product of 35 years' worth of research. I
- can't thank my PhD supervisor, Adrian, he's here in the audience. Thank you, Adrian, who really got
- me going on the road of science. Lots of people involved in that, I can't thank them. These are
- just the names of people involved in my slides that I've shown you today. I thank them. I'm more
- the cheerleader. I've always thought in my career that I've been a bit of an interloper. There have
- been smarter people next to me doing the real thinking. I was kind of like, listening in,
- and I found a photograph from the last century that I think kind of proves that. So there's me,
- and here are two smarter people. You may recognise them from the beer and the jumpers, and you can
- see I'm kind of listening in to their more wiser conversation. I'll stop there. Thank you.
- Thank you so much, Eddie, for an absolutely fabulous Croonian lecture. That vision of this
- huge depth of viral evolution that we just didn't know anything about until your group got on to
- it. So thank you very much. Absolutely wonderful. I'm sure there'll be lots of questions. So we've
- got roving microphones and there's one here.
- virological bias for human and mammalian viruses, what chance of serology in the
- workers on those farms, is that possible?
- at the moment, as you may well know. We're just about okay to do the animals, as long as we don't
- stray into COVID origins, it's okay. Workers, it's great, you're right, we should absolutely
- do that. I will raise it and see what I can do. It may be an ask too much, but we can certainly
- try, but you're right. It has to be done.
- H2 receptor. So what are the properties that make some viruses likely to jump?
- So generally, what makes it? So that's a good question. So some viral families appear to be
- jumpier than others, or rather when they jump, they're more likely to be successful. So for
- example, I've worked a lot on hantaviruses and they cause lots and lots of spill-over
- infections. So one person gets infected by an animal, but they almost never, ever seem
- to get going. Yet coronaviruses just appear to be very, very good at it, and they appear
- to jump much more frequently and successfully. Why is that? That's a hard question. It may be
- because they use more conserved receptors, and so if receptors are conserved between species,
- then it's easy for the virus to get in, and maybe the mode of transmission as well is different. So
- I don't think we really know that question. It's a really great question because it may then give
- us some guidance on what might emerge next.
- basically the viruses were evolving with the host, so they weren't jumping, they were
- evolving with them.
- sorry to interrupt, I think you're absolutely right. I think two things go on. These viruses
- are ancient, ancient things. Viruses are actually probably older than the first cells. I strongly
- suspect that viruses, RNA viruses are remnants of the RNA world that then got into cells later on.
- There's a backbone of that ancient history, you can see these ancient associations with
- millions and millions of years. On that backbone then you have jumping. So both processes go on.
- There's kind of a framework of viruses from the host evolution, yet then, they jump within that,
- and the closer the two hosts are the more likely the jump is going to work. So for example,
- we eat viral infected plant matter every day. We eat salads, but we never get plant viruses,
- because our cells are just too different.
- Todd from Oxford. So you think the RNA virus was before bacteria?
- Yes, again, this is mainly hypothesis, right? This is so ancient, but I suspect
- the first replicators were with RNA. So RNA can also catalyse. I suspect viruses,
- RNA viruses ultimately come from those early times and secondarily gone to cells, yes.
- I guess the answer is SARS-CoV-2 didn't come from the lab.
- Thank you. I really appreciate that question. My views on this are very well known. I think there's
- absolutely no evidence, scientific evidence at all, that puts it in that lab. If someone could
- show me any evidence for that virus in that lab prior to the pandemic, I'd be happy to believe it,
- but there's absolutely none and there's been four plus years of investigation.
- They found absolutely nothing. So all credible scientific evidence points to nature.
- Great lecture. I know you're RNA virus obsessed, but in the DNA world, there's this option of
- seeing both this sort of deliberate sampling to go hunting for viruses and then also compare it
- to just like sequencing seawater, and these sorts of things. I was just curious about,
- in that DNA world, what the - it's not quite a capture release scenario, but there are two
- different ways of trying to look at genetic material, including viruses. Does that give
- you any insight into what the space of, let's say, in this case, DNA viruses look like?
- It's a good question. I think the same is true for - I don't know DNA. That's mainly DNA phage.
- For RNA viruses, they do seawater studies. Every time you sample seawater, you get different
- viruses every single time. I don't think you ever sample the same virus twice, ever,
- and that's true of many of the species I look at. I never see the same virus twice. Drosophila,
- I think we know the drosophila virus. DNA viruses, I don't know so well. Maybe it's the
- case that… I need to go back and check. I think you'd find more of the same ones. I think that
- virus is probably smaller. I think you'd find the same sort of phage. RNA virus is not.
- We've got an online question here. Are ancient viruses discovered in
- permafrost included in your estimate?
- viruses in permafrost. I have to say, I will go off piece here a bit, there's been a lot
- of a lot of worry about permafrost melting, releasing deadly pathogens. I don't think
- that's a worry compared to the number of viruses found in other ecosystems. If you compare what's
- found in permafrost, to compare what you found in the tropical biodiversity hotspot, it's
- incomparable. So I'm not concerned about it, and it sounds good, but I'm not really concerned about
- permafrost viruses, although some may reappear.
- the outer reaches of the virosphere that you've been talking about?
- No, I don't think so. Humans have got a very predictable… So my students refuse to work on
- humans because they're so boring, because we find the same viruses every single time. No,
- I suspect disease X will be from a known family, and I suspect disease X will be respiratory
- because they're the ones we worry about, because they're the hardest to control, and then that
- puts it into one of three groups, influenza viruses, coronaviruses or paramyxoviruses.
- So they're the three diseases. I mean, there will be dengue and other arboviruses and Ebola, but I
- think they are controllable. The respiratory ones are the ones that I worry about, and I think there
- are three classes and they'll be the ones.
- types of creatures, mammals and aquatic animals. What are the most generalist types of viruses
- and why are they able to survive in these very, very different types of creatures?
- So what we've noticed, and I'll get corrected by the virologists in the room, what we've noticed
- is that the viruses we've found in environmental samples, so in seawater or in harsh environments,
- they often lack an envelope protein. So viruses, you have two different types. You have some that
- just have… All viruses have a genome that are capsid protein and a protein shell. Some have
- an extra envelope around that that's partly cell membrane and virus protein. The ones you find in,
- in environmental samples don't tend to have envelopes, because I think that's probably
- soluble and more fragile. The hardy ones just have the capsid. So picornaviruses,
- they're the ones we find. So they appear to be just better at surviving these sorts
- of environments. The envelope is great for getting in and out of animal cells,
- but it makes you more fragile as well, I think.
- raises the question, what is a virus? Are we now defining it as any genetic material of noncellular
- origin, or is there more to it than that?
- talk! Come on, Ollie, you know the answer more than me. I don't really know. I mean, I define
- viruses as being… Gosh, how do I define it? So basically, I mean, they replicate, they have an
- evolutionary history that involves RNA polymerase, right? That puts them in the virus world to me. If
- you're on that lineage, you're a virus as far as I see it, and that means you're living as well,
- by the way. I'm not a chemist. So I think if you have that ancestry, you're a virus. How far that
- goes back? So one thing we try to do, also as have others, is look for viruses in archaea. So
- we've looked in extreme halosphere, environments, salt lakes. We went to Lake Tyrrell in Australia,
- Antarctica has got salt lakes. We looked in those. We looked in extreme thermophile habitats. So we
- went to New Zealand, looked in geothermal pools, and they're dominated by archaea. So if you sample
- the metagenomic sequencing, you get all archaea. We're yet to find an RNA virus that we think is
- absolutely an archaeal virus. Is that because they're not there? Which I doubt because they
- have DNA viruses, or is it just because they're so divergent in sequence we can't see them? I
- suspect it's that. So finding an archaea virus, RNA virus would be a big thing to do. We've
- tried and haven't yet found it.
- this should be the last one. We can continue to discuss with Eddie.
- So two questions.
- The first one is, you believe, you have a hunch the next epidemic will be caused
- by another coronavirus. So is there any particular way to prove that?
- I would say coronavirus or influenza. Did you say prove it or prevent it?
- I'm not really sure. It's like, how could you be certain that that's a higher likelihood?
- Oh, I'm not certain at all, and one thing I definitely do not do is make predictions,
- okay? As Niels Bohr said, prediction is very difficult, especially about the future. So I
- don't know. I think you can say what general classes of viruses are likely to emerge,
- that much you can say. I think it's generally coronaviruses and influenza
- viruses I worry about. Where, what type, where, when? I have no idea. But I would
- worry about that HKNU5 in mink.
- why are viruses transferable between different animal orders when they have
- shorter lifespans or less capacity for variation, especially in RNA viruses?
- So cross-order jumping is actually… So all the virus wants to do, if I can anthropomorphise,
- is get into a cell, replicate and get out of that cell and move on. That's its life's goal. Now,
- what animal, that cell is in, is an immaterial, whether it's a human or Boris Johnson or a gopher,
- it doesn't actually matter, as long as it can find that cell and be exposed and replicate. It
- just turns out that the closer those cells are in their genetic makeup, the easier it is for them to
- get in. So a very, very general rule in virology is the closer the two hosts are, the more likely
- the viruses are to get infected. So for example, I've never seen a fish, I've sampled lots and lots
- of fish, I've never seen a fish virus jump into a human or a reptile virus. Bird virus is very,
- very rare. So avian flu, avian paramyxovirus. Human viruses are all mammalian on average.
- So there's a very general rule to that.
- now to the presentation. So the Croonian Medal and Lecture 2024 is awarded to Professor Edward
- C. Holmes for being a global authority on virus evolution and emergence, who played a key role
- in the discovery of SARS-CoV-2, and was the first to publicly released the genome sequence. Eddie,
- you have a medal and a scroll. Congratulations and thank you again for a wonderful lecture.
The Croonian lecture 2024 is given by professor Edward C. Holmes
Viruses are everywhere, yet we know remarkably little about them. In this lecture Professor Holmes will show how recent technological developments in ‘metagenomics’ have enabled scientists to glimpse the total universe of viruses - the virosphere - for the first time. This new research shows that viruses are far older, more diverse and more complex than we previously realised, and that their reputation for always causing disease is perhaps misplaced. Professor Holmes will discuss the major drivers of virus evolution, the role played by viruses within global ecosystems and how major events in animal evolution, such as the origin of the vertebrates, have shaped the diversity and evolution of the viruses they carry. He will show how advances in artificial intelligence are enabling scientists to describe the outer edges of the virosphere. Finally, Professor Holmes will discuss how new genomic technologies provide a powerful way to rapidly reveal the animal origins of infectious disease epidemics and track their spread through our species, including COVID-19.
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