After half a year of stormy debate, we are finally getting to see all the gory details about how two teams of scientists produced some disturbing flu viruses. I’ve written about this unfolding story previously here, at Slate, here again, in the New York Times, and back here again.
In tomorrow’s New York Times, I step back and take a look at the two published studies, and talk to experts about what those studies do–and don’t–tell us about how likely we are to face a new flu pandemic in the years to come. There’s still a huge amount about the flu that we don’t know yet, sorry to say. Check it out. (I also spoke with Times editor Michael Mason on this week’s science podcast. Listen here.)
Recently I stopped by the offices of PBS Newshour to talk with correspondent Hari Sreenivasan about viruses–from the bird flu that’s in the news today to the viruses that swarm the oceans. Here’s the video, and here’s their story about our conversation.
This month has seen a flood of new studies and reviews on the microbiome, the collection of creatures that call our bodies home. In tomorrow’s New York Times, I look at why scientists are going to so much effort to map out these 100 trillion microbes.
The microbiome is not just an opportunistic film of bugs: it’s an organ that play an important part in our well-being. It starts to form as we’re born, develops as we nurse, and comes to maturity like other parts of the body. It stabilizes our immune system, keeps our skin intact, synthesizes vitamins, and serves many other functions. Yet the microbiome is an organ made up of thousands of species–an ecosystem, really. And so a number of scientists are calling for a more ecological view of our health, rather than simply trying to wage warfare against infections.
We all started out as a fertilized egg: a solitary cell about as wide as a shaft of hair. That primordial sphere produced the ten trillion cells that make up each of our bodies. We are not merely sacs of identical cells, of course. A couple hundred types of cells arise as we develop. We’re encased in skin, inside of which bone cells form a skeleton; inside the skull are neurons woven into a brain.
What made this alchemy possible? The answer, in part, is viruses.
Viruses are constantly swarming into our bodies. Sometimes they make us sick; sometimes our immune systems vanquish them; and sometimes they become a part of ourselves. A type of virus called a retrovirus makes copies of itself by inserting its genes into the DNA of a cell. The cell then uses those instructions to make the parts for new viruses. HIV makes a living this way, as do a number of viruses that can trigger cancer.
On rare occasion, a retrovirus may infect an egg. Now something odd may happen. If the egg becomes fertilized and gives rise to a whole adult individual, all the cells in its body will carry that virus. And if that individual has offspring, the virus gets carried down to the next generation.
At first, these so-called endogenous retroviruses lead a double life. They can still break free of their host and infect new ones. Koalas are suffering from one such epidemic. But over thousands of years, the viruses become imprisoned. Their DNA mutates, robbing them of the ability to infect new hosts. Instead, they can only make copies of their genes that are then inserted back into their host cell. Copy after copy build up the genome. To limit the disruption these viruses can cause, mammals produce proteins that can keep most of them locked down. Eventually, most endogenous retroviruses mutate so much they are reduced to genetic baggage, unable to do anything at all. Yet they still bear all the hallmarks of viruses, and are thus recognizable to scientists who sequence genomes. It turns out that the human genome contains about 100,000 fragments of endogenous retroviruses, making up about eight percent of all our DNA.
Evolution is an endlessly creative process, and it can turn what seems utterly useless into something valuable. All the viral debris scattered in our genomes turns out to be just so much raw material for new adaptations. From time to time, our ancestors harnessed virus DNA and used it for our own purposes. In a new paper in the journal Nature, a scientist named Samuel Pfaff and a group of fellow scientists report that one of those purposes to help transform eggs into adults.
In their study, Pfaff and his colleagues at the Salk Institute for Biological Sciences examined fertilized mouse eggs. As an egg starts to divide, it produces new cells that are capable of becoming any part of the embryo–or even the membrane that surrounds the embryo or the placenta that pipes in nutrients from the animal’s mother. In fact, at this early stage, you can pluck a single cell from the clump and use it to grow an entire organism. These earliest cells are called totipoent.
After a few days, the clump becomes a hollowed out ball. The cells that make the ball up are still quite versatile. Depending on the signals a cell gets at this point, it can become any cell type in the body. But once the embryo reaches this stage, its cells have lost the ability to give rise to an entirely new organism on their own, because they can’t produce all the extra tissue required to keep an embryo alive. Now the cells are called pluripotent. The descendants of pluripotent cells gradually lose their versatility and get locked into being certain types of cells. Some become hematopoetic cells, which can turn into lots of different kinds of blood cells but can no longer become, say, skin cells.
Pfaff and his colleagues examined mouse embryos just after they had divided into two cells, in the prime of their totipotency. They catalogued the genes that were active at that time–genes which give the cells their vastly plastic potential. They found over 100 genes that were active at the two-cell stage, and which then shut down later on, by the time the embryo had become a hollow ball.
One way cells can switch genes on and off is producing proteins that latch onto nearby stretches of DNA called promoters. The match between the protein and the promoter has to be precise; otherwise, genes will be flipping on at all the wrong times, and failing to make proteins when they’re needed. Pfaff and his colleagues found that all the two-cell genes had identical promoters–which would explain how they all managed so become active at the same time.
What was really remarkable about their discover was the origin of those promoters. They came from viruses.
During the earliest stage of the embryo’s development, these virus-controlled genes are active. Then the cells clamp down on them, just as they would clamp down on viruses. Once those genes are silenced, the totipotent cells become pluripotent.
Pfaff and his colleagues also discovered something suprising when they looked at the pluripotent ball of cells. From time to time, the pluripotent cells let the virus-controlled genes switch on again, and then shut them back down. All of the cells, it turns out, cycle in and out of what the scientists call a “magic state,” in which they become temporarily totipotent again. (The pink cells in this photo are temporarily in that magic state.)
Cells in the magic state can give rise to any part of the embryo, as well as the placenta and other tissue outside the embryo. Once the virus-controlled genes get shut down again, they lose that power. This discovery demonstrated that these virus-controlled genes really are crucial for making cells totipotent.
Pfaff and his colleagues propose that the domestication of these virus promoters was a key step in the evolution of mammals with placentas. The idea that viruses made us who were are today may sound bizarre, except that Pfaff is hardly the first person to find evidence for it. Last year, for example, I wrote about how placental mammals stole a virus protein to build the placenta.
A discovery this strange inevitably raises questions that its discoverers cannot answer. What are the virus-controlled genes doing in those first two cells? Nobody knows. How did the domestication of this viral DNA help give rise to placental mammals 100 million years ago? Who knows? Why are viruses so intimately involved in so many parts of pregnancy? Awesome question. A very, very good question. Um, do we have any other questions?
We don’t have to wait to get all the answers to those questions before scientists can start to investigate one very practical application of these viruses. In recent years, scientists have been reprogramming cells taken either from adults or embryos, trying to goose them back into an early state. By inducing cells to become stem cells, the researchers hope to develop new treatments for Parkinson’s disease and other disorders where defective cells need to be replaced. Pfaff suggests that we should switch on these virus-controlled genes to help push cells back to a magic state.
If Pfaff’s hunch turns out to be right, it would be a delicious triumph for us over viruses. What started out as an epidemic 100 million years ago could become our newest tool in regenerative medicine.
(For more on these inner passengers, see my book A Planet of Viruses.)
[Image: Courtesy Salk Institute.]
In the past few weeks, there’s been a string of horrific tales of cannibalism and other zombie-esque behavior in the news. How to explain a handful of reports of people doing the unspeakable? One answer circulating around these days is that it must be parasites. And for some journalists, the question demands a call to the Centers for Disease Control to find out what they’re hiding from us!
1. Andy Campbell of the Huffington Post asked the CDC if some kind of zombie virus was to blame for the recent attacks. On June 1, he reported on HuffPo’s Politics page the following scoop:
“CDC does not know of a virus or condition that would reanimate the dead (or one that would present zombie-like symptoms),” wrote agency spokesman David Daigle in an email to The Huffington Post.
The Huffington Post entitled Campbell’s hard-hitting investigation, “Zombie Apocalypse: CDC Denies Existence Of Zombies Despite Cannibal Incidents.” That’s perhaps the finest deployment of the word despite in the history of journalism.
The story, by the way, received 65,797 likes on Facebook.
2. The Daily Caller picked up Campbell’s expose later that day, essentially reposting his whole piece. But Daily Caller reporter Michael Bastasch also salted his cut-and-paste with a few pieces of his own research. For example, Bastasch reports, some people “have claimed it was caused by the LBQ-79 virus.”
The Daily Caller headline: “CDC: No zombies, despite cannibal attacks.”
Can’t those pointy-headed government pencil-pushers see what’s in front of their own dismembered noses???
3. Andy Campbell must have bitten Michael Bastasch’s ear, because the idea of parasite-induced zombification has infected the editorial offices of the Daily Caller. On June 4, a minute before midnight, Josh Peterson, Tech Editor at the Daily Caller, posted a new story:
Clearly, this story could not wait for the morning, presumably because zombies prowl the night.
Here’s how last night’s story starts:
The Centers for Disease Control and Prevention (CDC) recently denied knowing of “a virus or condition that would reanimate the dead (or one that would present zombie-like symptoms),” after a series of instances of cannibalism across the country were reported, but remains silent about the effect of zombie-inducing parasites that live in human brains.
The parasite is Toxoplasma gondii. Lifting material reported here at Discover, Peterson describes how Toxoplasma alters rat behavior, reducing their fear of cats, the final host for the parasite. About one in five humans carries Toxoplasma too, as do many mammals, including pigs.
Now–watch as Peterson makes an Olympic-quality pivot off of the pig and back into the horde of zombies:
While pigs are known to engage in cannibalism, no known correlation between the parasite and cannibalism has been found.
France also has a high prevalence of Toxoplasma-infected people.
The Daily Caller’s inquiry to the CDC about why it omitted parasites from its denial, and about the possibility of the cannibals having been infected by the Toxoplasma, however, was met with silence.
Silence! Perhaps the CDC spokespeople simply couldn’t pick up their phones, because they were busy holding their heads in their hands, wondering how their clever zombie attack survival guide had gotten them into this mess, and how they’re going to get out of it.
As someone who has written a lot about the sinister powers of parasites, I’d be right in the thick of it to report on any genuine information on a zombie-parasite outbreak–if there was one. But there isn’t. While some people may laugh off these “reports” from the Daily Caller or the Huffington Post, others may take them–or subsequent rumors–seriously. So let me just lay out the reality of what parasites can do to the brain:
1. Some parasites do control the brains of their hosts. There are viruses and fungi that drive their insect hosts to the tops of plants, so that the parasites can shower down on new hosts, for example. Some flatworms that infect fish cause them to thrash around at the surface of the water, to make them easier pickings for birds, inside of which the flatworms can reproduce. Parasitic wasps rob cockroaches of their will, so that the wasps can lay eggs on them, which then invade their docile host. Other parasitic wasps turn their hosts into bodyguards. After they emerge from caterpillars, their dying hosts fight off other insects that would try to eat the pupating wasps. It’s important to note that the most extreme examples of host manipulation come from tiny-brained animals such as insects or fish–not people.
2. A cannibalistic zombie is no benefit to a parasite. Host manipulation generally shows all the signs of natural selection at work. Mutations to genes in the parasites gradually give them the ability to alter the behavior of their host more and more, in ways that boost the odds that the parasite will be able to reproduce. But what possible good could come from a parasite that caused its host to kill other people? That just robs you (the parasite) of a potential host. Not smart. And so it should come as no surprise that scientists have never found a parasite that causes cannibalism. (Tasmanian devils spread cancer to each other by biting each other’s faces, but they don’t need cancer’s help to get into fights. The cancer cells just go along for the aggressive ride.)
3. Fine, but what about rabies? The rabies virus is pretty creepy, both in its manipulation of its host and in its deadliness. You get rabies from the saliva of an infected animal that bites you, and the virus then slips into the nervous system. Rabies infection makes animals aggressive–and thus more likely to bite new victims. The horror of rabies infection has haunted us for thousands of years (for more, check out the wonderful book, Rabies: A Cultural History of the World’s Most Diabolical Virus by Bill Wasik and Monica Murphy, coming out next month. Wasik, an editor at Wired, sent me the book a few months back, and I loved it.)
But the reality is that rabies does not produce armies of human zombies trying to bite other people. It is possible to get infected by someone’s saliva, but it’s an extremely rare occurrence. We humans are a dead end for the virus. It depends on other animals to continue circulating from host to host.
And, again, let’s think this through. Rabies is 100% deadly unless you get treated. But it stays in circulation because its hosts remain alive long enough to bite other animals before they die. Dismembering a victim and eating him for dinner, or chewing off his face under a Florida overpass are not going to do a virus much good.
4. But what about the LBQ-79 virus? I read about it on the Daily Caller! Couldn’t that be a rabies-like virus that makes people cannibalistic zombies? There is no such thing.
5. But there is such a thing as Toxoplasma, right? Absolutely. Toxoplasma is one of my favorite parasites. And there’s a lot of evidence now that it can influence human behavior–albeit in subtle ways. Kathleen McAuliffe lays out the current science nicely in this story in the March issue of the Atlantic.
But again, let’s work through this. Toxoplasma only alters its animal hosts to make them easier prey for the parasite’s final host. All effects on humans seem to be pale shadows of that strategy. (And, just like rabies, we are a dead end for Toxoplasma.) So how do we get from making your host easy prey to becoming a zombie cannibal?
Also, bear in mind that the parasite dwells in the brains of over a billion people. It’s been there for centuries, if not thousands of years. Only now is it suddenly turning people into cannibals? No self-respecting science-fiction scriptwriter would try pitching that idea to Hollywood. Unfortunately, the editors at the Daily Caller have lower standards than that.
[Update: I originally wrote that Bastasch was the author of the second Daily Caller story. Fixed. Also, I accidentally block quoted some of my own text, giving the impression it was in the Daily Caller. Fixed.]
[Second update, 5:10 pm: On Twitter, Peterson responded to this post by writing, "Nice piece, but why'd you leave out the parts about it being related to mental disorders?" and, later asking, "So you're content in not explaining the effect of the parasite on the brain in your piece, then?"
In case I wasn't clear enough by linking to McAuliffe's story, let me be clear now: a number of studies suggest that an exposure to Toxoplasma may influence people's personality. It has also been identified as a risk factor for schizophrenia. Here's one recent review in Developmental Neurobiology that presents evidence of a raised risk in people who were exposed before birth. (Other studies have found that other infections can also raise the risk.)
But I find Peterson baffling. Is he suggesting that we can explain an outbreak of cannibalism by pre-birth exposure to Toxoplasma, leading decades later to schizophrenia, leading to cannibalism? If so, it's not only ridiculous, but it's insulting to the 2 million people who suffer from schizophrenia in the United States, as well as their families.]
Why do flu shots only protect us for a single season? Why can’t influenza vaccines be like polio vaccines: get them in childhood and be done with them? Wouldn’t that be the best way to prepare ourselves for the next pandemic?
These are among the questions that will be addressed at next month’s World Science Festival. To lay the groundwork, I’ve written a blog post at the festival web site on where we stand on the road to a universal flu vaccine. At this point, we have good reason to believe that such a vaccine could be invented. Which makes it all the more urgent that we do so. Check it out.
At some of my recent talks, I’ve been running into people who’ve been annoyed that they forgot to bring a book of mine to get signed. You really couldn’t think of a better way to cheer up a writer, and so I feel the need to reciprocate.
So if you’ve gotten a book of mine and want to get it signed, I’ve printed up some bookplates that I can autograph and send to you.
Just to ensure I’m not signing bookplates for alien robots who will take these bookplates to their home planet to…do whatever evil thing alien robots do with bookplates from science writers…please follow these steps:
1. Take your picture with the book.
Optional step 3. For those on Twitter: instead of emailing me your photo, you can upload it to Twitter (mentioning my Twitter name @carlzimmer). Be sure to email me your address, too, so that I know where to send the bookplate.
So far, I’ve got three bookplates–one for Parasite Rex, one for Science Ink (in matching Goth type), and one for Planet of Viruses. (See below). It’s weirdly easy to produce these things, so I’m happy to take requests for my other books.
Viruses are everywhere: scientists have found them under Antarctic ice; they lurk inside your lungs which until recently were believed to be sterile; and seawater, which was once thought to contain very few, has now been found to be teeming with viruses. In fact, they outnumber all other residents of the ocean by 15 to 1. Even the human genome contains genes that came from viruses which infected our ancestors some 30m years ago, an idea that Zimmer describes as “almost philosophical in its weirdness.” In this succinct yet elegantly written survey, he explores the vital role viruses play in the evolution of life on Earth and how scientists have begun to reveal their often deadly secrets. Smallpox – the only human virus to have been eradicated – killed an astonishing 500m people every century in Europe between 1400 and 1800. From the common cold, first described 3,500 years ago by the Egyptians, to a new type of giant virus discovered in a Bradford water-cooler that mimics bacteria, this book is a fascinating and enlightening introduction.
Ed Yong and I may live on either side of the Atlantic, but our minds are in the same place: that strange realm where fungi take over the minds of ants, where dinosaurs sprout feathers, and where ducks shatter glass with their genitals. In other words, Earth.
We don’t get to see each other in person more than once a year, if that, but we always have a good time when we do. Which is why I’m looking forward to having an online conversation with Ed on May 14. And you’re invited.
This event is brought to you by Shindig, a new company that’s set up a web site for video chat events. The design of the site is quite elegant: the speakers appear on the top of the event page, where everyone can watch them talk. Audience members appear in their own screens on the page as well, and when speakers ask for questions, they can hit a “raise hand” button. The audience member asking a question then zooms up to the top of the screen, where he or she can have a conversation with the speaker. (You’ll obviously need a video camera and mic on your computer to take advantage of this feature.)
There are lots of things for us to talk about, such as the controversy over manmade strains of bird flu. But we’ll be happy to talk about other things biological that are on your minds, too. So bring your questions (or offer some suggestions in the comment thread below.)
We will be talking on Monday May 14 from 5 to 6 pm ET. To join us, please RSVP at this eventbrite page. The talk is free, of course, but after you RSVP you’ll then get instructions for logging into the Shindig page on May 14.
This is 100% experimental, but I expect it to be fun. It reminds of Bloggingheads, but without the creationism.