Singularity Summit 2012

Our Viral Future


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Speaker: Carl Zimmer

Transcriber(s): Marius van Voorden and Ethan Dickinson

Moderator: Carl Zimmer is our next guest. He is a popular science writer and blogger, focused on evolution, medicine, biotechnology, and natural history. He is a frequent contributor to the “New York Times”, “National Geographic”, “Scientific American”, and “Discover Magazine”, where he is a contributing editor, and writes the award-winning blog “The Loom”. He appears regularly on National Public Radio, and is a lecturer at Yale University. He has written 12 books, including “Evolution: the Triumph of an Idea”, and has twice won the Journalism Award from the American Association for the Advancement of Science. Please give a warm welcome for Carl Zimmer.


Carl Zimmer: Good morning. I’d like to start today by introducing you to somebody who had very many interesting names. He was known as “the Repulser of Millions”, “the Lord of the Two Lands”, “the Son of the God Ra”. I’m talking about Ramses V, the pharaoh of Egypt from 1149 to 1145 BC. We don’t know a lot about his life. Apparently there was a civil war during his reign. He was buried two years after his successor took over which suggests that he didn’t meet a very good end, but we know some interesting things about how he died.

We know it because in 1979, a doctor named Donald Hopkins got permission to examine his mummy. He had been dead for over 3,000 years, but Hopkins was still able to examine him and discovered something very interesting. As you can see in this picture, there are pockmarks all over his face, and Hopkins saw yellow pustules on his shoulders and his chest, over much of his body. Hopkins knew what this was, this was smallpox. This actually makes Ramses V very important in the history of human civilization. For one thing, he is the oldest person with evidence of a smallpox infection, so we know that over 3,000 years ago, people were dying of smallpox. Bear in mind that this was a pharaoh. This was perhaps the most powerful man in the world at the time, but all that power and all that wealth couldn’t protect him from a microscopic particle.

Today I want to talk about the future of viruses, but as we’ve seen in a number of the talks here, sometimes the best way to talk about the future is to look at the past. The past of viruses actually tells us a lot about how they will continue to have a very important part in our life, but maybe one that you’re not expecting.

The virus that killed Ramses is smallpox. Viruses in general are pretty much the same. Sir Peter Medawar, a great immunologist summed it up very nicely when he said that a virus is a piece of bad news wrapped up in a protein.

This is the flu. This just happens to be a nice diagram, it’s got a few genes inside and it’s got a protein shell on the outside, which has special proteins for locking on to cells and invading them. They have an incredibly beautiful simple way of replicating. They invade cells, they unload their genes and some of their proteins, and then the cell itself is basically forced into making new viruses.

In the case of smallpox, people pick it up often through the mouth, it disseminates throughout the body, and then eventually it produces scabs, which is how it is able to go and transmit to another person. It kills about 30 percent of its victims, and it has been staggeringly successful at killing people. There was one estimate that during the 1400s, the 1500s, the 1600s, in Europe alone, five million people died of smallpox every year. When Europeans came to the New World, they brought among other viruses smallpox which killed millions, maybe tens of millions Native Americans, we really don’t know how many. Suffice to say that this is a virus that has killed billions.

It was probably in China or India that someone got the idea of actually inoculating people with smallpox virus to trigger an immune response that would protect them. It was a tricky thing to do. Side effects included death. [laughs] Edward Jenner in the late 1700s got the better idea of actually doing a vaccine using a much milder virus related to smallpox, cowpox, because he noticed that the milkmaids around his village never seemed to get smallpox. That was because they were basically getting vaccinated by their cows.

Now, the invention of technology – and this is technology – does not automatically solve a problem. Smallpox did not immediately disappear. In fact, even in the 20th century 300 million people died of smallpox. The reason that we beat smallpox, is that we had vaccines, we improved the vaccines, and then there was a massive global campaign to get rid of it.

This is just one poster from part of that campaign. It started in the 1960s and by 1980 smallpox had been eradicated from the face of the Earth. There are now only two stocks of smallpox that are known of. One is here in the United States, one is in Russia. In the wild it has been driven extinct. We live in a post-smallpox world.

This is the first time that we have been able to rid ourselves of a virus. We just witnessed the second eradication of a virus: rinderpest. Rinderpest infects cows, and is completely devastating to herds of cattle. This is a picture from the 1890s when a rinderpest outbreak killed almost all of the cows in Southern Africa. It was staggering in its lethalness. Then in 2011, after another long global campaign, rinderpest has been completely eradicated. It’s gone.

We’ve seen a lot of curves at this meeting, and I have some curves to show you as well. In the case of, say, computing, the curves might show the power that your computer has over the years. It becomes more and more powerful. The curves that I can show you are ones that go down. Smallpox goes from being incredibly common to zero. Rinderpest goes to zero. Here’s polio, which had put Franklin D. Roosevelt in a wheelchair. It’s not at zero yet, but thanks to a vaccine and another public health campaign, it’s getting very close. In fact, polio only really survives in certain areas that are war-torn or where there is opposition to using the vaccine, like certain areas of Pakistan.

Perhaps one of the most important curves I can show you is this one. HIV had since 1981 been one of the top killers in the world, and unfortunately year after year, more and more people each year would get infected with it. That actually started to crest in the 1990s and it’s slowly falling. The deaths from HIV seem to have crested as well. Partly that’s because we have the invention of anti-viral drugs that can stop HIV from killing people. You can’t get rid of the virus yet, but at least hold it in check and keep people’s health up. We might be looking at the start of another one of these downward curves. There’s a lot of optimism about new treatments that might actually lead to it being eradicated.

In the future actually I think one of the biggest benefits we’re going to get in terms of treating viruses are in terms of viruses that you might not even realize are viruses. There are viruses that cause cancer. Perhaps the most famous one is human papillomavirus which can cause cervical cancer. Rebecca Skloot’s bestselling book, “The Immortal Life of Henrietta Lacks,” is about the origin of an experimental line of cells, the HeLa cells, which came from a woman who died of cervical cancer. What happened was that a virus invaded her cells, and turned them cancerous. They grow so fast that they still grow, 50 years after her death.

There are actually a lot of cancers like this, caused by viruses. About a million and a half people die every year of them, it’s estimated. Perhaps more. This is 15 percent of all cancers. As opposed to other cancers, which might have environmental causes, this is a cancer you can vaccinate. We can vaccinate people to get rid of cervical cancer, and it will be gone. We can probably vaccinate against other cancers as well, and you can expect that in the future.

That might have filled you with optimism and hope. You could think of our world of viruses as a bucket, and we’ve drilled holes in it and the bucket is draining out, and soon it will be empty and everything will be great. Unfortunately the bucket is under a faucet. We are having new viruses enter our lives. Adapting to our species, and making life difficult for us.

Actually HIV itself is a great example of this. This is an evolutionary tree, and those three black dots show you several times in which HIV jumped from chimpanzees to humans, mutating, evolving, adapting, to our biology. Not only do we know now that it came from chimpanzees, but we know when, and we know where. The worst form of HIV crossed over from chimpanzees to humans in that little red circle there.

[a red circle is shown in southeast Cameroon]

Carl: Probably a hunter hunting for chimpanzees, some blood got into a cut, perhaps, and then the virus started adapting. As you can see there’s a river that connects that circle to Kinshasa, which was then known as Léopoldville in the early 1900s. Kinshasa is where the first major urban center of HIV infections came. You can see how HIV got a foothold, as it were, in our species thanks to what we were doing. Thanks to 20th century colonialism, deforestation, building railways and traffic systems, growing populations. All of this is really great for a virus.

This was not some isolated incident. Just 10 years ago there was the SARS outbreak. This was a virus that no one had seen before. It came out of nowhere. By the time it was done, 8,098 people were sick, 774 of them died. Scientists were saying “Where did this come from?” Again they looked at the virus, they looked at its DNA, and they compared it to other viruses to see if they could find relatives. They looked in animals. They found it in palm civets, which are animals that are sold in market places in China, where the outbreak occurred.

Then scientists made a complicated evolutionary tree which I show you here. Basically this is just what you need to see. Humans and palm civets, yes they both got SARS, but they got it from something else. They got it from a bat. Bats, now, are proving to be a really wonderful source of new viruses, if you like that sort of thing. We beat SARS, but we didn’t do it with a vaccine. We just used quarantine, which is something we’ve known about over 600 years, since the Black Death. We were lucky, because SARS shows its symptoms quickly, and if you quarantine people they can’t transmit it. It’s never come back.

That being said, there will be more viruses. Just last year, for example, farmers in Europe, actually around a small village in Germany, started noticing these horrific birth defects, they’d never seen before. Devastating, stillborn deformities, damage to the nervous system and so on. It started off in summer and just took off. It spread to other countries, and as you can see here that was the spread of this mysterious disease just in a matter of months.

Scientists looked at these dead sheep, these dead cows, and they tried to figure out what was causing it. Again, they found a virus. This is a virus that had never been seen before. They called it the Schmallenberg virus, named after the village in Germany, where they had first discovered the symptoms. This is another evolutionary tree, which kind of gives scientists a clue about where it came from. Just a little clue though, because what’s weird is that the closest relatives of the Schmallenberg virus are in Japan. No one can really tell how Schmallenberg evolved from these Japanese viruses, and how it ended up in Europe.

One thing they do know is that it gets spread, not by a cough, not through blood contact, but by insects. It’s kind of like West Nile disease. West Nile is spread by mosquitos, Schmallenberg virus is spread by midges, which are mosquito-like insects. In any case, these midges go from flock to flock, some of them probably got swept across the English Channel, to England, where they started infecting animals in southeast England there. Over the winter midges died off, lambing season was over, so you didn’t see many cases of it. People thought maybe we dodged this bullet. Not the case. This year it came back and it’s spreading even more. In England, for example, it spread all the way through England, and went into Wales, and now it’s at the border of Scotland, and the Scottish farmers are very nervous. This looks like it could well be a fixture of life in Europe, a virus that did not really exist a year ago.

I could give you plenty of other examples. I don’t know if you’ve read about a virus that's spread by ticks, that was discovered in Missouri. It was just reported a couple of months ago. There’s a new hemorrhagic virus found in Africa, causes lots of horrific bleeding. If you read about enough of these new viruses you can freak out a little, which is probably why there have been so many great movies about viruses that have been made.

We should be concerned. I mean, we have to be concerned, because we know that a lot of new viruses have crossed over into our species over the past century, and we don’t have a whole lot of great treatments for them. There is no treatment for SARS, for example, except for quarantine. We don’t know what to do about it.

That being said, I don’t think that we should feel totally hopeless. In fact, we should have a lot of confidence. There are things that we can do now, that Edward Jenner, say, couldn’t. For example, we can sequence their genes very quickly. Here’s another curve. This shows the number of viruses whose genes have been sequenced, and it’s exploding. A mysterious disease like Schmallenberg shows up and... [snaps fingers] can get identified and sequenced in a matter of weeks or even days. This is a huge advantage we have. We have this incredible power.

Again, you have to bear in mind that it doesn’t matter how fancy your car is. Who’s steering it? What are they doing? We don’t know a lot, unfortunately, about some of the most worrisome viruses. We don’t have particularly good monitoring systems in place. The flu, for example, spreads from birds to people. Fresh waves of flu virus cross over every now and then. There’s one called H5N1, that scientists are – very – worried about now. We have a very thin monitoring of where it is now. It just pops up in different countries, we don’t know why, we don’t know how it’s mutating, we just don’t know what’s going on.

What we need is better monitoring and we need more innovative research. For example, flu viruses, if you got your flu shot, and I hope you did, that was grown in a chicken egg, which is what people did in the Eisenhower administration. It's incredibly slow, it takes months to breed up these vaccines. What we need are better ways, faster ways of making vaccines. A company called Medicago, for example, is doing some really innovative work, actually producing vaccines in genetically engineered tobacco plants, which grow quickly, and you can grow a whole bunch of tobacco plants. You don’t have to be sitting around waiting for chickens to lay their eggs.

We need all of this, I just want to stress, because we have so many viruses out there. Real quickly, I’ll give you a sense of the places that you can find viruses. You can find them a mile underground, in the water in subterranean caves. You can find them at the South Pole in the ice, where they’re infecting bacteria that live there. You can find them inside of us. We have trillions of viruses inside of us when we’re healthy. A lot of them infect the bacteria in our bodies, some of them infect our own cells and yet don’t make us sick.

This is how many viruses it turns out that there probably are on Earth, 10 ^ 31. It’s kind of hard to give you a sense of how big that is. One way of thinking about it is saying “Okay, let’s take all the viruses on Earth and stack them one on top of the other. How far can we go?” The answer is 200 million light years.

There are a lot of viruses out there and we’re not going to get rid of them all. It would be foolish to think we could. Perhaps a better way of dealing with them is to find a peaceful solution, where we can shield ourselves from the worst of them and take advantage of all the incredible experimentation that they have evolved.

I’ll just give you a couple examples before I stop. There is a virus that insects insects, caterpillars. It causes them to climb up to the top of trees, where the caterpillars then explode and release the viruses down on the caterpillars below. It’s wonderfully horrific. [laughs] It turns out to be a great way of making proteins, because the viruses make protein balls to embed new viruses, so if you just genetically engineered them, put them in a cell culture, and you could make any protein you want. This is a billion dollar industry now.

Gene therapy is made possible in many cases because viruses are so good at pasting DNA into other genomes. All the great advances we've had recently with gene therapy have come largely with the help of viruses as our little genetic engineers. Angela Belcher at MIT is doing mindblowing stuff using viruses’ ability to bind to things. She’s actually using viruses to assemble solar cells, and create more efficient ones than we’ve made before.

I can’t tell you that in two years from now we’re going to be facing an outbreak from some South American bat that’s going to kill 83.7 percent of the human population. [laughs] I can’t tell you when HIV will be eradicated from the face of the Earth. One thing I can say, is that viruses are going to be surprising us in the future. What I hope is that at least some of those surprises will be pleasant ones.

Thank you very much.


[Q&A begins]

Man 1: Thanks. You talked a little bit about how the development of human infrastructure and intercontinental travel and deforestation serves as an accelerant for the spread of viruses, but wouldn’t you also say that now our global interconnections of communication serve as a way to much better monitor the viruses? Rapid genomic sequencing with handheld devices, isn’t that something that would have as big a – positive – effect as intercontinental travel?

Carl: That’s a good point. It – could, – if we actually lived in a world where there were virologists with handheld devices doing that right now. That’s not reality right now. There’s the potential to take advantage of that, but it’s not happening yet. Which is a shame, because the system is all there in place, and we could use it.

I would say that you’re starting to see some of the glimmers of that. I think one of the most interesting examples of that was in 2009, when we had this new strain of the flu pop out of nowhere. Scientists again were saying “What is this thing? What kind of flu is this? Where did it come from?” They figured it out very quickly, just in a matter of a couple of weeks. There was an international collaboration, basically being done by a bunch of different research centers, who were pooling their findings on a wiki which was completely open. Anybody could watch their progress as it was happening. They nailed it, they figured out how it had evolved from a pig virus, and so on. I hope that there’s more of that in the future, but just because the potential is there, doesn’t necessarily mean that people take advantage of it.

[next question]

Man 2: How much sleep do you lose when thinking about, this century, the ability of humans and scientists to create a virus that is detrimental to our species and can wipe out a billion people?

Carl: The question of actual synthetic biological warfare is an important one. I think I get more sleep about it now than I used to. Part of what led me to that was reporting for the New York Times and elsewhere about some experiments on the flu, where scientists were taking this bird flu I mentioned, H5N1, and they were tinkering with it, adding in mutations to try to figure out, well, what is it that makes it able to cross over and become a mammal-to-mammal flu. There was a huge concern about this, "Oh, if you publicize these details, then anybody could just take this and run with it, and synthesize this virus and then just have a grand old time with it."

I have to say that I think a lot of the loudest voices are the least rational about this. In the sense that, people were saying, “Oh you know, some garage biologist could do this.” I talk to scientists about what it actually takes to make flu viruses and that’s not true. At least in the state of synthetic biology right now, you can’t do this sort of thing in your garage.

Maybe 20 years from now you will be, obviously all these curves are moving, so that is a possibility. But then we have to wonder about the rationality of the people doing it. If you are a terrorist and you decide to turn bird flu into the next pandemic, you’re probably the first one who’s going to die. Not only that, but if you go and try to release it in a country that you despise, we know from past flu epidemics that within a few weeks, it'll be back in your country. It spreads so fast. There might be some completely nihilistic maniacs who might want to do this, but then I feel like we’re in a James Bond movie at that point. I think of them as an incredibly small probability and incredibly high risk prospects we’re looking at, so they're very hard to judge. But we know for a fact that viruses do very well at crossing over on their own, and that’s definitely going to happen in the future. That’s what keeps me up at night more.

[next question]

Man 3: Just a quick clarification, was the 10 ^ 31 viruses, was that individual viruses, or different virus genomes?

Carl: That’s the estimate of how many individual viruses, virus particles there are. As to how many species of viruses there are, it’s hard to say. First of all it’s hard to say what it means to be a virus species, but what is clear is that most of the world’s genetic diversity is in viruses. If you were to make a catalogue of every different gene on Earth, the majority of them would be from viruses. I didn’t really have a chance to talk about this, but viruses are hugely important as a force in the evolution of life over the past few billion years. They move genes around to different hosts. They’re like a repository of life’s genetic information.

[next question]

Woman 1: You just sort of answered my question a little bit, but I’ve heard that there are about 10 ^ 30 bacteria on the planet, and that about a third of them are taken out by viruses every day?

Carl: [nods]

Woman 1: I was wondering if you could speak to the amount of protein novelty that viruses may or may not be creating on the planet. A lot of people think that evolution at the protein level might be happening in eukaryotes or whatever, not realizing.

Carl: Viruses themselves are evolving very quickly to adapt to their hosts. Every now and then, some of their genes end up – in – their hosts, and that includes us. About eight percent of the human genome derives from viruses that infected us and like HIV can insert their genes into our genes. A lot of that is just baggage, it doesn’t do anything, but some of them have been co-opted and actually serve a function for us. For example, the human placenta needs a virus protein in order to stick properly to the uterus. Our ancestors got infected with this virus protein maybe 50 million years ago. None of us would be here, if not for that infection, if not for that virus.

In terms of your other question, yes, bacteria are by far the most abundant hosts for viruses, because there are just so many of them, all over the place. There are lots of viruses that infect them. It’s generally pretty bad to get infected with a virus if you’re a microbe, because you just explode when it’s done. You just burst open with new viruses. In the ocean, bacteria just burst open, as you say, a third, I’ve even heard some people say a half maybe, of bacteria get killed every day in the ocean. There’s a huge amount of bacteria in the ocean. All that carbon’s getting dumped out, and it probably has a huge effect on the climate. It’s possible the carbon is going back up into the atmosphere, where it can trap heat, or it’s possible it gets rained down to the bottom of the ocean. Nobody knows yet, but there is probably a virus-climate connection. They’re a planetary force.

Moderator: Unfortunately we are out of time. Carl Zimmer, great talk. Thank you so much for being here.

Carl: Thank you very much.