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The Race To Create The Best Antiviral Drugs
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The Race To Create The Best Antiviral Drugs


The Race To Create The Best Antiviral Drugs
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This is FRESH AIR. I'm Terry Gross. Ever since the discovery of penicillin in 1928, antibiotics have helped us fight bacterial infections. But scientists are still trying to find ways of effectively fighting viruses. Our guest, science writer Carl Zimmer, writes about efforts to develop antiviral treatments in the current edition of Wired.

As you'll hear, some of the approaches are particularly creative, like encouraging a cell that's been infected by a virus to commit suicide so the virus can't use it to replicate and spread to other cells. Carl Zimmer is a lecturer at Yale University and the author of 12 books, including "A Planet of Viruses." He writes a blog called The Loom at, and his articles appear in many publications, including the New York Times, National Geographic, Time and Scientific American. He spoke with FRESH AIR contributor Dave Davies.

DAVE DAVIES, BYLINE: Well, Carl Zimmer, welcome to FRESH AIR. Let's begin with a couple of basics - the difference between bacteria and viruses. How are they different, fundamentally different?

CARL ZIMMER: Well, bacteria, believe it or not, are a lot more like us than viruses are. Bacteria are big cells that have DNA in them and protein in them. They can feed. They can grow. They can build their own proteins, and then they can divide. They can live on their own, essentially.

Viruses are very different. Most of them are just protein shells with genes inside, kind of - you can think of them as shells, like little hard balls that go into much bigger cells, and the shells break open, and inside are the genes for the virus. And those genes then essentially take over the cell and start using it to manufacture new viruses.

And then they break out of the host cell to go off and infect other host cells, and maybe then you get a bad cough or a runny nose, and you release the viruses to go infect somebody else.

DAVIES: Right. Now, the broad-spectrum antibiotics that exist, like penicillin and others, can kill all kinds of bacteria. Do the existing antiviral drugs destroy or attack a lot of different viruses, or are they specifically targeted toward a unique virus?

ZIMMER: So there are some really amazing antivirals that have been invented over the, say, last 40 years. So there are antivirals for herpes, for example. There are antivirals for HIV. Now, if a person is infected with HIV, they can take antivirals that will keep their virus under control. They won't wipe them out, but it will allow someone to have a relatively long, relatively healthy life.

Now, if you were to get Ebola, which is caused by a virus, and you tried to take those HIV drugs, they'd do you no good at all because that HIV drug, it only works for HIV. So in other words, it's a narrow-spectrum drug, and really there are no broad spectrum antivirals, at least at this point.

DAVIES: Right, and you've written recently about efforts to develop new treatments which will really attack viruses more broadly. There are three of them that you describe in this piece in Wired. Let's take them one at a time. One of them, developed by this scientist and his sister, focuses on, what, the external shell of the replicated virus. Explain how this works.

ZIMMER: Sure, so this approach was developed by Vishwanath Lingappa and his sister Jaisri Lingappa, and the basic idea behind it is that viruses need help to build themselves. It used to be thought that once a host cell made new copies of virus genes and made new virus proteins, that basically the virus could take it from there, that the molecules would just spontaneously come together and form new viruses. It was called self-assembly.

And what the Lingappas showed is that that's actually wrong, that the viruses need a little help. And what happens is quite amazing. They actually somehow get lots of different proteins in our cells to come together and cooperate to sort of push their own proteins into place, like putting together a very complicated puzzle. And so the viruses need these groups of host proteins to form.

DAVIES: So how do they stop the virus, all these different viruses?

ZIMMER: Well, it seems that a lot of viruses depend on some of the same host proteins to get built. And so if you just create a drug that kind of gets in the way and prevents the viruses from pulling in these host proteins to do these cooperative jobs, you don't get any viruses.

And so that also means that this is an approach that might not have very many side effects because all you're doing is stopping proteins coming together to make new viruses; that's it.

DAVIES: So we could take a medication that would enter our healthy cells, wouldn't damage the cells, but would somehow prevent the proteins in them from helping a virus to get in and replicate?

ZIMMER: That's right. Once the virus was in and was trying to use your cell to make new viruses, this drug would just step in and just stop that little manipulation. And that would be it. And that's enough, apparently, to stop viruses. And for example, Lingappa has worked with Army researchers on an animal test on Ebola, and so what they did was inject mice with Ebola virus, and if the mice were not protected, in 10 days they were all dead.

Then what they did was injected one of these drugs that Lingappa's discovered into another group of mice, once a day for four days, and they got 100 percent protection. So you have all dead mice and all living mice. And so, you know, again, these are preliminary results, but they're very promising.

DAVIES: There's a second approach that you write about in which some other researchers are dealing with interferons, ways that our body naturally attack viruses. Do you want to explain how they work?

ZIMMER: Yeah, so like the Lingappas, other scientists want to figure out how to use our own bodies to kill viruses. And actually our own bodies are killing viruses all the time. And one of the most important ways that they do it is with a molecule called interferon.

So what happens when you get infected, when a virus comes into a cell, is very often there's a protein in your cell that can recognize, say, a virus protein or a virus gene, and it essentially sets off an alarm in your cell, and the cell makes this wonderful protein called interferon. And interferon then does all sorts of things to fight off the virus.

It basically switches on about 300 genes in the cell, and they do all sorts of different things. One of the things that they do is they cut up virus DNA. So any virus genes that are floating around get sliced up into bits so that they're useless.

Another thing that interferon does is it stiffens the wall of the cell where the viruses are so that the viruses can't get out. And then finally, one of the coolest things that they do is that the interferons actually go out of the infected cell and go to neighboring cells and basically give them the signal and say kill yourself.

So all these cells around the infected cell commit suicide, and it's like a firebreak so that any viruses that might get out have nothing to infect.

DAVIES: OK, and one of the key researchers here is Eleanor Fish, right? What has she managed to do?

ZIMMER: So Eleanor Fish at the University of Toronto is in charge of a program called The International Consortium of Antivirals. And what they would like to do is they would actually like to create a synthetic interferon, so an interferon that you could take, you know, as a pill or an injection or so on.

And actually, this is part of a long-running line of research on interferon. People discovered interferon in the 1950s, and it was so amazing that they thought that they had actually discovered the key to fighting viruses and that this would be kind of like a penicillin.

It's been very difficult to live up to that dream. Today, people with Hepatitis C can get interferon treatment, but it's - it doesn't work all that well. I mean, it has some benefit, but it's not as good as Eleanor Fish would like.

And so what she's been doing is she has been essentially tweaking the interferon molecule to make it more effective, to make it last longer, to make it safe and to make it cheap, because what she wants to do is to be able to deploy interferon all over the world, in very poor parts of the world where there isn't fancy refrigeration. She wants to be able to help people who are dealing with viruses in very remote places.

DAVIES: There's another fascinating approach to fighting viruses that you describe in this piece, and it involves, well, what, cell suicide?

ZIMMER: That's right. This is an approach that is probably the most radical of the three that I talk about in the article because it really involves just making a molecule from scratch that manipulates our body in a totally new way.

It's the work of someone named Todd Rider, who works at MIT, and Todd got the idea for this while he was developing a biowarfare-type detection machine, essentially a machine that you would set up like in government buildings to detect if someone had released anthrax or some other kind of agent.

And it occurred to Rider that, you know, if they detected anthrax, they could do something about it. You could give people antibiotics. But if it was, say, for example, smallpox, there's really nothing you can do. There's no antiviral for smallpox. And the idea he got was that, you know, our cells, you know, they can recognize viruses when they come in because viruses have special kinds of genetic material.

And so what he did was he fashioned a molecule that could latch on to that genetic material, and on the other end of this molecule it could essentially act as a switch to switch on genes that would cause the cell to kill itself. So as soon as a virus infects a cell, the cell kills itself, the virus can't replicate, we're done.

DAVIES: And how do you get a cell to kill itself?

ZIMMER: Well, you know, actually, our cells have a bunch of genes in them that are just about suicide. Actually, it's very important for your cells to be able to kill themselves, and the reason is that, you know, every now and then you might get a mutation that might cause your cell to start growing and dividing too fast, in other words to become cancerous.

So if that happens, you need a way to stop it. And so one of the ways to stop it, is to switch on this program for cell suicide. And there are actually other situations where it's beneficial for your body, just in the normal business of living your life, for your cells to kill themselves.

And so what Todd Rider is doing is exploiting that. He's basically kind of hotwiring your cells so that as soon as they get infected by a virus, that trips the switch. This doesn't exist naturally, but if you were to take a pill, the thinking is, then this molecule would go into your infected cells and as soon as they detected the virus, they would kill the infected cell and you would recover from your disease.

DAVIES: We're speaking with science writer Carl Zimmer. He's written recently in Wired about some innovative strategies to fight viruses. We'll talk more after a break. This is FRESH AIR.


DAVIES: If you're just joining us, we're speaking with Carl Zimmer. He's a science writer who has an article in the current edition of Wired about innovative efforts to fight viruses. His book, "A Planet of Viruses," will be out soon in paperback.

If we did have, you know, drugs which allowed us to attack viruses in our bodies, all kinds of viruses, is there any risk that we could attack viruses that might be helpful to us?

ZIMMER: That's a possibility, and it's pretty amazing that, you know, we can even talk about that. I mean, that's one of the really interesting things about these new results. I mean, these scientists are getting real broad-spectrum effects. They can wipe out lots of different viruses.

And so it does raise an intriguing question: Do you want to wipe out all viruses? And I think antibiotics, you know, teach us a kind of cautionary lesson here because, you know, antibiotics, when you take them, you wipe out the bacteria that's making you sick, but you actually also wipe out a lot of bacteria that you depend on for your health.

And you know, eventually your body may recover, but it can take a while, and there may be some bad consequences of the antibiotics themselves. So it's going to be interesting to see what happens in the future if we are, in fact, you know, knocking out lots of viruses, because we really don't understand sort of understand the full ecology of the viruses that get into our bodies.

Some are harmful, some may not be harmful. Some may actually help us to defend against other viruses. It's very complicated in there, and we don't really understand it very well yet.

DAVIES: You said there are bacteria that contribute to our health?

ZIMMER: Absolutely. So you and I and everybody else, we each have about 100 trillion bacteria in our bodies. We only have 10 trillion cells, human cells. So you know, we're 10-to-one bacteria. They cover our skin. They line our mouths. They're in our lungs. They're in our stomachs and our intestines. They're everywhere.

And in a lot of those places, they seemed to be doing some very important things. So in our guts, for example, they make vitamins. They actually create a kind of defensive wall that keeps out the bacteria that would make us sick. And they even teach our immune system to behave properly.

And if you don't have healthy gut flora, you can actually end up growing up and developing asthma or allergies. There's been some connections between these bacteria and how well our immune system works when we grow up.

DAVIES: Do we know if there are viruses that are helpful to us as well?

ZIMMER: Well, there are certainly viruses that attack those bacteria. In fact, each of us has about four trillion of those viruses, which are called phages. Now, they don't care about us. They can't infect our cells. They're going after the bacteria. And they might be kind of like the lions of our inner ecosystem, and so they're keeping different prey species in check. And so maybe our health depends on those viruses that are attacking those bacteria.

It's also possible that there are viruses that infect human cells that are, you know, either not having any effect on us, they're just sort of neutral, or perhaps even helping us in some way we don't understand. Scientists are finding that in other animals there are some beneficial viruses. So it's possible.

DAVIES: We have four trillion viruses or four trillion different kinds of viruses?

ZIMMER: We have four trillion viruses, if you just count them one by one. Nobody can quite say how many species they are, but it would probably be in the hundreds, hundreds of species of viruses. We might have 1,000 or more species of bacteria in our bodies.

DAVIES: So these microbes, these microscopic organisms, bacteria, they're everywhere in our bodies. Do they live in colonies? Do they function together in groups?

ZIMMER: So these bacteria probably live mostly in films. Actually, they create these films themselves. They will produce lots of sticky molecules that glue themselves together, and so you'll have these layers of bacteria lining your teeth, lining your throat, lining your lungs, lining your gut, lining your skin too.

And they are sitting there feeding off of the food that you take in or whatever nutrients they can come across, and then some of them will actually feed on the waste of other species. And so you will have bacteria of lots of different species in these bio-films, and in a lot of cases they're going to be cooperating across the species barrier.

DAVIES: The rainforest in the fold of my thumb, huh?

ZIMMER: Absolutely, absolutely. Like, you could think about the sharks that have the remora fish stuck on them, and then the remora feed on the, you know, the bits of food that the sharks don't eat. Well, there are bacteria that do exactly that, where one species takes the waste of another species and feeds on that. And they produce waste that another species feeds on.

And then guess what? When you finally get down to the end of that chain of breaking down food into waste, we eat what they leave behind.

DAVIES: Our cells do...

ZIMMER: That's right. So especially when it comes to tough plant matter, we can't eat it. We actually depend on our bacteria to help break it down, and once they've taken apart these molecules into smaller sugars, then we can feed on them because we just don't have the enzymes that bacteria have. We don't have the genetic versatility that bacteria have.

And if you think about it, if there are perhaps 1,000 species, who knows, maybe 2,000 species of bacteria in our bodies, and each one of those species has, say, a couple thousand genes, you're talking about a collective genome that dwarfs the human genome. It might be 100 times bigger.

So if you were to grind up our bodies and just count out all the genes, it would be one percent human genes and maybe 99 percent microbe genes. And so we're sort of a super-organism.

DAVIES: Now, if there are many times as many microbes as there are human cells, do they compare in mass and volume? I mean, or are the human cells bigger?


ZIMMER: Human cells are maybe 10 or 100 times bigger than bacteria. So if you took all the bacteria in our bodies and kind of just molded them together, you would have about three or four pounds of biomass. And you can think of that as like an organ, like your heart or your brain. So you've got this three or four pound organ in your body that we call the microbiome, but instead of being one big mass of cells, it's diffused out throughout your entire body.

DAVIES: These are microscopic organisms. They include bacteria and other things, is that right?

ZIMMER: So we've got bacteria in us, we've got viruses, we've got fungi, we've got other kinds of microbes that are called archea and protozoans. we've got a whole zoo in there. And this is when we're perfectly healthy. This is not - these are not things that are making us sick. In fact, if you took all these things out of us, we would probably get sick very quickly because the bad - the pathogens would be able to come in and take over.

GROSS: Science writer Carl Zimmer will continue his conversation with Dave Davies in the second half of the show. Zimmer's article about research into antiviral drugs is in the current edition of Wired. I'm Terry Gross and this is FRESH AIR.


GROSS: This is FRESH AIR. I'm Terry Gross. Let's get back to the interview that FRESH AIR contributor Dave Davies recorded with science writer Carl Zimmer who has been writing about how bacteria and viruses attack our body and strategies to fight them. His article about research into new antiviral drugs is in the current edition of Wired.

DAVIES: You've written, recently, about microbes in the body and the fascinating ways that they may harm us, help us and define us. And there's a fascinating case in 2008 of a woman in Minnesota who was severely ill with some I guess, what gastrointestinal infection. You want explain what was going on with her - what happened?

ZIMMER: Sure. So this was a woman who had taken antibiotics for a lung infection and the antibiotics worked; they got rid of the lung infection and unfortunately, they killed off a lot of good bacteria in her intestines, allowing bad bacteria - in this case, a species called the Clostridium difficile - to take over and to cause a very serious infection. This caused massive diarrhea and she was losing weight practically every day. She had lost 60 pounds in a matter of a couple of months. The bacteria was resistant to all antibiotics. And so her doctor, Alexander Khoruts, at the University of Minnesota, really was kind of at his wits end. I mean there was not much else that he could do and, you know, she was probably going to die very soon.

And so what he decided to do was try out an experimental technique that people have tried from time to time in different parts of the world. The thinking is that if you can restore the ecology of a person's body, then that ecology will make these bad bacteria go away. And the way that he did this, is that he performed what's called a fecal transplant. And what that means is that he took a small stool sample from her husband and diluted it, and then gave it to her, kind of like as a suppository. The bacteria in that sample then colonized her intestines. And literally, two days later she started feeling better. And a couple of weeks later when they went to sample the bacteria that were there they couldn't find the C. difficile anymore. It was just gone. And all they...

DAVIES: The harmful bacteria. Right. Yeah.

ZIMMER: Right. So they couldn't find the harmful bacteria anymore. It had just disappeared. And the only thing they had done is that they had essentially restored her ecology, kind of like restoring a wetlands.

DAVIES: So the theory is that the treatment for the lung problem had, kind of, upset the ecological balance there, by killing certain bacteria she needed and this harmful bacteria flourished. And then, by introducing microbes from her husband's intestine, the ecology was restored and the harmful bacteria was taken out?

ZIMMER: That's right. I mean, actually, there are a lot of parallels with kind of ecology that we think of, you know, when we're thinking of say, lakes and prairies and so on. And it's well-known that in an ecology that has been fragmented and degraded and lost a lot of species, it's easy for invasive species to come in. It's actually easier for them to come into these degraded ecosystems than healthy ones. And so this woman, by taking antibiotics, had actually degraded her ecosystem, her micro biome - these microbes - so that they couldn't create a kind of defensive of wall to keep out the bad bacteria, like Clostridium difficile. And so, by restoring these species that had been kind of pushed out after a while, they were able to create a kind of ecosystem that could fight against the bad bacteria and make it harder for that to replicate.

DAVIES: And much do we understand about how these microbes interact?

ZIMMER: We know next to nothing about how these microbes interact. This is one of the frontiers of biology, I think, because we don't even have really a good catalog of all the species that are in us. And so, you know, you and I probably have kind of an overlapping catalog of microbes that are in us, but they're not the same. And, you know, if the person next to you, if you look at their catalog they would have a somewhat different one. And nobody quite knows why we have these different species and different levels and so on, but they've got to be doing something. And the fact is that bacteria are incredibly cooperative. Very often, one species cannot survive without several other species, because they work together. They break down compounds together and share them. And so there's this whole ecosystem interaction that's going on inside our own bodies that we do not understand - barely at all. Scientists are just starting to figure it out with very big projects where they are sequencing all the genes that these microbes have, but they're just at the very beginning of understanding it.

DAVIES: And you write that different parts of the body will have different, kind of, combinations of microbes, and that even different sides of a tooth will have a different combination of species.

ZIMMER: That's right. It seems like the microbes are carving us up into incredibly fine niches. And so, yeah, different sides of your teeth are different ecological niches for the bacteria, and different species do better on one side of your tooth than the other. And that are on your fingertips versus on your palm, versus on the back of your hand, they're different and they're adapted to these different kinds of temperatures and pH levels and all the rest.

DAVIES: How common are fecal transplants now?

ZIMMER: Fecal transplants are still pretty much under the radar. There have been, I believe, a few hundred of them tried out in various parts the world. There's no kind of official way to do them. I mean basically doctors do them when other things have failed. But there have been some published reviews where scientists have looked at case reports and they find that they're quite effective - something like 90-95 percent effective. The problem is, as some other journalists have reported, is that the FDA has a very difficult time figuring out how to come up with regulations for this. And so before it's going to become a very widespread standardize kind of practice, the FDA is going to have to move beyond its old paradigm of just giving people kind of regular drugs, to being able to give people sort of tailored concoctions of living things of bacteria - maybe even viruses - as medical treatments.

DAVIES: Well, Carl Zimmer, it's been really interesting. Thanks so much for speaking with us.

ZIMMER: Oh, thank you for having me.

GROSS: Carl Zimmer spoke with FRESH AIR contributor Dave Davies. Zimmer's article on antiviral drugs is in the current edition of Wired. You'll find a link on our website, Zimmer's book, "A Planet of Viruses," will be published in paperback later this month.

Coming up, the great Dutch jazz drummer Han Bennink plays a drum and some other stuff sitting around our studio. This is FRESH AIR.


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