If not for a virus, none of us would ever be born.

In 2000, a team of Boston scientists discovered a peculiar gene in the human genome. It encoded a protein made only by cells in the placenta. They called it syncytin.

The cells that made syncytin were located only where the placenta made contact with the uterus. They fuse together to create a single cellular layer, called the syncytiotrophoblast, which is essential to a fetus for drawing nutrients from its mother. The scientists discovered that in order to fuse together, the cells must first make syncytin.

What made syncytin peculiar was that it was not a human gene. It bore all the hallmarks of a gene from a virus.

Viruses have insinuated themselves into the genome of our ancestors for hundreds of millions of years. They typically have gotten there by infecting eggs or sperm, inserting their own DNA into ours. There are 100,000 known fragments of viruses in the human genome,  making up over 8% of our DNA. Most of this virus DNA has been hit by so many mutations that it’s nothing but baggage our species carries along from one generation to the next. Yet there are some viral genes that still make proteins in our bodies. Syncytin appeared to be a hugely important one to our own biology. Originally, syncytin allowed viruses to fuse host cells together so they could spread from one cell to another. Now the protein allowed babies to fuse to their mothers.

It turned out that syncytin was not unique to humans. Chimpanzees had the same virus gene at the same spot in their genome. So did gorillas. So did monkeys. What’s more, the gene was strikingly similar from one species to the next. The best way to explain this pattern was that the virus that gave us syncytin infected a common ancestor of primates, and it carried out an important function that has been favored ever since by natural selection. Later, the French virologist Thierry Heidmann  and his colleagues discovered a second version of syncytin in humans and other primates, and dubbed them syncytin 1 and syncytin 2. Both virus proteins seemed to be important to our well-being. In pre-eclampsia, which gives pregnant women dangerously high blood pressure, levels of both syncytin 1 and syncytin 2 drop dramatically. Syncytin 2 also performs another viral trick to help its human master: it helps tamp down the mother’s immune system so she doesn’t attack her baby as a hunk of foreign tissue.

In 2005, Heidmann and his colleagues realized that syncytins were not just for primates. While surveying the mouse genome, they discovered two syncytin genes (these known as A and B), which were also produced in the same part of the placenta. This discovery allowed the scientists to test once and for all how important syncytin was to mammals. They shut down the syncytin A gene in mouse embryos and discovered they died after about 11 days because they couldn’t form their syncytiotrophoblast. So clearly this virus mattered enormously to its permanent host.

Despite their name, however, the primate and mouse syncytins didn’t have a common history. Syncytin 1 and 2 come from entirely different viruses than syncytin A and B. And the syncytin story got even more intricate in 2009, when Heidmann discovered yet another syncytin gene–from an entirely different virus–in rabbits. While they found this additional syncytin (known as syncytin-Ory1) in a couple different species of rabbits, they couldn’t find it in the close relative of rabbits, the pika. So their own placenta-helping virus must have infected the ancestors of rabbits less than 30 million years ago.

Now Heidmann has found yet another virus lurking in the ancient history of mammals. This one is in dogs and cats–along with pandas and hyenas and all the other mammals that belong to the so-called carnivoran branch of the mammal tree. In every carnivoran they’ve looked at, they find the same syncytin gene, which they named syncytin-Car1. In every species it is strikingly similar, suggesting that it’s experienced strong natural selection for an important function for millions of years. But it’s missing from the closest living relative of carnivorans, the pangolins. The diagram here, from the authors, shows how they see this evolution having unfolded. After the ancestors of carnivorans split from other mammals 85 million years ago, they got infected with a virus which eventually came to be essential for their placenta.

The big picture that’s now emerging is quite amazing. Viruses have rained down on mammals, and on at least six occasions, they’ve gotten snagged in their hosts and started carrying out the same function: building placentas. The complete story will have to wait until scientists have searched every placental mammal for syncytins from viruses. But in the meantime there is something interesting to consider. Some mammals that scientists have yet to investigate, such as pigs and horses, don’t have the open layer of cells in their placenta like we do. Scientists have come up with all sorts of explanations for why that may be, mainly by looking for differences in the biology of each kind of mammals. But the answer may be simpler: the ancestors of pigs and horses might never have gotten sick with the right virus.

(For more information on our inner viruses, see this 2010 story I wrote for the New York Times and my book from last year, A Planet of Viruses.)

[Top image: Leonardo da Vinci's sketch of a human fetus. From Universal Leonardo]

I’ve posted a batch of autographed, hardback editions of A Planet of Viruses in my Amazon store. You can have your own inscribed copy for ten dollars plus shipping. Click here to order.

For those unfamiliar with the book: it’s a linked collection of twelve essays on twelve viruses. I use each one to illustrate a broad lesson about viruses in general, such as the fact that they are the most abundant life form on Earth and that they make up a sizable portion of the human genome.

The Washington Post wrote: “In A Planet of Viruses, science writer Carl Zimmer accomplishes in a mere 100 pages what other authors struggle to do in 500: He reshapes our understanding of the hidden realities at the core of everyday existence.”

PS: The paperback edition will be coming out this spring.

Michael Osterholm, his face a pink-cheeked scowl, looked out across the table, beyond the packed room at the New York Academy of Sciences, and out through the windows. The New York Academy of Sciences is housed on the fortieth floor of 7 World Trade Center, and their endless bank of windows affords a staggering view of Manhattan, Brooklyn, and New Jersey. One reason that its view is so magnificent is that there’s a huge gap in the skyline–and a huge gouge in the ground–where the Twin Towers once stood.

Osterholm had come here from Minnesota, where he runs a research center for infections diseases and terrorism, to talk Thursday night about the threat of a new kind of flu sitting in labs in the Netherlands and Wisconsin. In nature, it’s a flu that spreads easily between birds but doesn’t travel well from human to human. The Dutch and Wisconsin scientists had found ways to get this bird flu, known as H5N1, to move between ferrets. For Osterholm, ferrets were uncomfortably close to humans on the evolutionary tree. And so he, along with other members of an advisory board, issued a recommendation in December that key information in the papers about the research should be left out.

Osterholm looked out at the empty space beyond the windows. “Who would have imagined that you could use box cutters to take down the World Trade Center?” Osterholm asked. The risk from the new bird flu might seem equally unlikely, he warned, but it could end up being far more devastating. “We can’t afford to be wrong.”

The bird flu controversy first started to bubble up in September, when Ron Fouchier of the Erasmus Medical Center in Rotterdam described some of his unpublished results at a scientific meeting in Malta. It kicked into high gear when the National Science Advisory Board on Biosecurity issued their ruling, which Fouchier and Yoshihiro Kawaoka have agreed to. In January, the researchers agreed to stop doing any H5N1 research for two months, during which time the scientific community would try to come up with a plan about how to deal with such controversial research.

Viruses very often spark controversies, but often the controversy is between the scientists who study them and groups of people beyond the academy. Think of HIV denialism, of the non-existent link between vaccines and autism, of the purported connection between the XMRV virus and chronic fatigue syndrome. The new bird flu controversy is different. It’s split the scientific community wide open. I’ve written about this controversy in recent weeks over at Slate, as well as here at the Loom. Like most reporters covering the story, I’ve sampled the sharply opposing viewpoints of scientists over the phone or via emails. But on Thursday night, we got to see this debate in person. The New York Academy of Sciences brought together a group of experts to talk about new virus, and whether self-censorship is a prudent protection or a dangerous precedent. I wasn’t sure what to expect; I was a bit worried it might have turned out to be a fairly dry discussion of how to inspect the hood equipment in virus labs. Instead, we witnessed explosive confrontation between scientists who think we may be facing a world-destroying catastrophe, and others who think our fear of non-existent threats is going to destroy science’s power to help us out of clear and present dangers.

The panel included two members of the National Science Advisory Board on Biosecurity: Michael Osterholm and Arturo Casadevall of Albert Einstein College of Medicine. They both made it clear that they were speaking at the meeting as individuals, rather than as official spokesmen for the board. But they presented a fairly united front. The board has been around for eight years, and it has only considered issuing a recommendation twice. The first time was in 2005, when scientists unearthed the bodies of victims of the 1918 flu epidemic, which killed an estimated 50 million people. The researchers isolated the 1918 virus and sequenced its genes. The board decided they had no objections about publishing the research. But six years later, they decided that, as bad as the 1918 flu might have been, the risk of an H5N1 outbreak was worse.

One big factor in their recent decision was the mortality rate when H5N1 gets into people. The World Health Organization’s official estimate is 60%. The 1918 flu, by contrast, had a death rate of about two percent. If H5N1 could gain the ability to spread among humans–either naturally, or through a lab experiment–it could bring that fearsome death rate to the entire world. “It’s the lion king of infectious diseases,” Osterholm said, no doubt dismaying Disney lawyers across the country.

Sitting a few seats down the panel from Osterholm was Peter Palese, one of the world’s leading experts on flu, who works at Mount Sinai Medical School. Palese disputed Osterholm’s apocalyptic warnings. Where Osterholm burned hot, Palese kept cool, but he did not hide his utter rejection of the board’s decision. Just because a flu virus can be transmitted by another mammal species, he argued, doesn’t automatically mean it can spread among humans. In fact, ferrets are rather delicate in the face of a flu infections, easily suffering from brain damage. Our closer relatives among the primates, by contrast, don’t get sick from flu at all. (Jon Cohen explores the ferret question in depth in a news article for Science.)

Palese also questioned whether H5N1 is all that dangerous. He argued that the World Health Organization based its mortality rate only on the people who came into hospitals and tested positive for H5N1. But this particular strain of bird flu mostly strikes people in poor countries, especially in southeast Asia, where medical services are scarce. The people who make it to a hospital could well be a small fraction of all the people who come down with H5N1.

“The asymptomatic people are not being counted,” Palese said. If those extra people only got sick for a few days and then got on with their lives, the true mortality rate might be far less than 60% “It’s really much lower,” he said, pointing to surveys in Thailand and other countries that revealed evidence that a fair number of people had been exposed to H5N1 at some point in the past. (Palese recently published this same argument in the Proceedings of the National Academy of Sciences.)

This argument positively enraged Osterholm. He had clearly read Palese’s recent PNAS commentary and had prepared a rebuttal. “What you’re saying is just propaganda,” he told Palese. The trouble with Palese’s numbers were that they came from lousy studies, Osterholm argued. There are many ways to overestimate how many people have been exposed to a particular virus. A common test involves fishing for antibodies in blood samples. If your test isn’t precise enough, you may end up dredging up antibodies to other viruses. Osterholm had gone through surveys of H5N1 exposure, setting aside the lousy studies and tallying up the results from the best of the bunch. He came up with an estimate of .6% or less. If very few people have been exposed, the recorded deaths from H5N1 represent a frighteningly high rate.

Casadevall granted that perhaps H5N1 wasn’t 60% fatal. But it could be half that and still be a planetary nightmare. Even if it was ten times lower, it would still be far worse than the 1918 flu. “The numbers of unbelievable, any way you look at it,” he said.

Palese was unmoved. The new H5N1 viruses might pose a risk–a small one, in Palese’s mind–but scientists could handle it. All the research that had triggered the controversy wasn’t conducted in someone’s backyard. It was carried out in well-protected labs. Palese noted that the board doesn’t seem to have any objections to the work that’s done these days on smallpox, a virus that killed millions of people every year until it was eradicated in the 1970s. If scientists can in fact safely experiment with dangerous viruses, there is no need to paralyze the scientific community over bird flu. “You can always assume the worst,” Palese said. “But where do we stop being afraid?”

Osterholm glowered at Palese. “You do not represent the mainstream of influenzologists when it comes to this issue on influenza,” he said. I glanced at some of the other journalist in the audience, wondering if Osterholm could see us scribbling notes.

Osterholm stressed that he was not against research on bird flu in general. He just wanted the scientific community to balance the potential costs and benefits. He didn’t see very much significance in the new bird flu work. It wouldn’t help public health workers monitoring H5N1 viruses for lineages that might be evolving into a human pathogen. Nor did he see any benefit for developing vaccines or antivirals. On the other hand, he saw a risk–a small one, possibly–of tremendous devastation.

But when it comes to viruses can we really calculate such ratios of costs to benefits? Vincent Racaniello, a Columbia University virologist who was also on the panel, doesn’t think so. We’re bad at estimating risks. In 1981, for example, Racaniello and his colleagues pioneered a method for making polio viruses: they stuck the virus’s genes on a ring of DNA called a plasmid, which they then inserted into E. coli bacteria. The engineered E. coli spewed out polio genes, which Racaniello could insert into human culture cells, which then made full-blown polio viruses. People worried that Racaniello’s bacteria would get into people’s guts and start a polio epidemic. (It didn’t.)

We’re also bad at determining the benefits of research. Racaniello recalled how microbiologists in the 1950s discovered that E. coli defend themselves against invading viruses by chopping up their genes. Nobody thought much of that discovery for over a decade. But then in the late 1960s, a few researchers realized that they could use E. coli’s enzymes to cut up DNA and then paste them into new combinations. The entire biotechnology industry was born from that late eureka.

“You could have never predicted that,” said Racaniello. “You never know who will do the right experiment. So that’s why you need to give the information to everyone.”

The way things stand right now, everyone will not be getting that information. I tried to follow the reasoning for holding back key parts of the studies, but, honestly, I can’t recount it in a way that makes sense. As far as I could tell, the thinking was somebody just fooling around out of curiosity would be able to use the full information to create a deadly flu. But the fact is that the scientists who produced the new bird flu used standard methods that have been published many times over. I was also confused by how Nature and Science, the two journals where the redacted papers are to be published, will handle distributing the information to those who need to know about it. An editor from Nature talked about how hard it would be to set up a system. I had been expecting them to have a system to unveil for us.

“None of us ever wants to see a redaction again,” said Casadevall. The most sensible way to avoid that would be to figure out a way to make decisions about risks and benefits much earlier in the life cycle of an experiment. If the mission of an experiment is to create a deadly virus, just to see if it can be done, the panelists agreed that that is probably not a study to run. But what kind of system can stop not just these experiments, but other experiments that might present unexpected dangers? Casadevall worries that every graduate student may have to fill out 100-page forms for even the most harmless of experiments. “You’ll kill science,” he said.

Casadevall was expressing a concern that all the scientists on the panel shared: they worry that this affair will keep them from doing research. For now, they’re trying to work out a fairly self-regulating system to handle this sort of controversial research, perhaps in the hopes that the government won’t come sweeping in. But there was one non-scientist on the panel who did her best to make the scientists aware of the world outside their community.

Laurie Garrett, an award-winning health reporter who now works at the Council on Foreign Relations, pointed out that the flu is not just something that American scientists study in their labs. It’s a global problem. There’s a huge amount of resentment in poor countries where bird flu is the biggest threat, not just to humans, but to the poultry industry. “Poor people are killing their chickens for you,” Garrett said. “They’re going bankrupt.”

Making matters worse, as Garrett has recently written, is the distrust that has developed in the developing world towards Western medical research and the pharmaceutical industry. Indonesia, where many of the H5N1 deaths have occurred, has been reluctant to share bird flu samples with Western scientists, for fear that they would make huge profits from vaccines developed from them. The World Health Organization has set up an international agreement for the exchange of wild bird flu strains between different countries, but it’s in fragile shape.

So for all the sparks that flew in New York Thursday night, the real fireworks over the flu are yet to come.

[Update 2/3 9 am: Corrected description of Racaniello's experiment. Thanks to Matt Frieman. 2:50 pm Fixed Fouchier's institution name and month of his talk. Thanks to Jon Cohen. 8 pm: Expanded Osterholm's "mainstream of influenzologists" quote after seeing his objection to a similarly truncated version in Christine Gorman's story for Scientific American and reviewing my own recording. It's a valid clarification .]

Charles Darwin recognized that natural selection can make eyes sharper, muscles stronger, and fur thicker. But evolution does more than just improve what’s already there. It also gives rise to entirely new things—like eyes and muscles and fur. To study how new things evolve, biologists usually have to rely on ancient clues left behind for hundreds of millions of years. But in a study published today, scientists at Michigan State University show that it’s possible to watch something new evolve in front of their eyes, in just a couple weeks.

The scientists were studying a virus, which evolved a new way of invading cells. As a result, their research not only sheds light on a fundamental question about evolution. It also suggests that it may worryingly easy for viruses such as influenza to turn into new epidemics. Check it out.

[Image of lambda virus: AJC1 on Flickr via Creative Commons]

Today, a company called Ion Torrent announced they were going to start selling a DNA-sequencing machine that can sequence an entire human genome for $1,000. It’s just the latest milestone in the long-term crash in the cost of gene-reading. There are lots of benefits that will flow from this ongoing transformation. For one thing, as I wrote in 2010 in the New York Times, it’s getting easier to identify new viruses that could turn to be the next HIV or SARS.

To research my story, I paid a visit to the Center for Infection and Immunity at Columbia University. On the day I dropped by, Ian Lipkin and his colleagues were very busy:

Some researchers were examining New York flu, others African colds. The blood of patients with mysterious, nameless fevers was waiting to be analyzed. There was dried African bush meat seized by customs inspectors at Kennedy Airport. Horse viruses, clam viruses: all told, members of Dr. Lipkin’s team were working on 139 different virus projects. It was, in other words, a fairly typical day.

Some of the research that was going on that day–specifically, the research on JFK bushmeat–was published today in the journal PLOS One. The Columbia researchers collaborated with a network of other scientists at the Centers for Disease Control, the Wildlife Conservation Society, Tufts University, the American Museum of National History, and the EcoHealth Alliance to do the first pilot study of the viruses that are carried from country to country by the wildlife trade.

They undertook the study because many of the world’s worst diseases are the result of pathogens switching from animal hosts to us. HIV started out as a chimpanzee virus, which first infected hunters in Cameroon. SARS started in bats, and then spread to palm civets, which then transmitted the virus to people in Chinese animal markets. There’s no reason to think that we’ve seen the last virus jump to our species. So scientists are starting to set up monitoring programs, in the hopes of reducing the chance that the next spillover is not a complete surprise.

As illustrated by HIV and SARS, a lot of viruses come our way through trade in animals. At first, this trade was small-scale. A hunter might come out of the jungle and barter some monkey meat for shoes. Chinese animal markets bring animals from hundreds of miles away. And today, with planes hopping between continents every day, the wildlife trade is now moving animals–and the viruses they carry–around the planet. About 120 million live animals are illegally imported into the United States every year, along with 25 million kilograms of meat and other wildlife remains. The animals that customs agents seize come most often from countries such as China, Hong Kong, and Nigeria–countries that plagued with some of the most worrisome animals viruses, such as Nipah virus and the H5N1 bird flu. It’s likely that West Nile virus first came to the United States in a bird destined for the pet trade; after first showing up in 1999, it’s now found throughout much of the country. Yet nobody has systematically looked at the viruses being brought into the United States through the bushmeat trade.

The authors of the new study studied wildlife products seized  by customs agents at JFK airport between 2008 and 2010, and later also looked at additional seizures in Philadelphia, Washington, Houston, and Atlanta. (The gruesome picture above, from the paper, is a primate head seized at JFK.) All told, they looked at 44 animals. Nine were primates, and the rest of were rats. The scientists isolated DNA from the meat to identify which species it came from. Their sources including chimpanzees and several species of monkeys.

The scientists then fished for genetic sequences of viruses. As they report today, they found a bunch. All nine primates the scientists studied had viruses in them–a variety of simian foamy viruses, cytomegaloviruses, and lymphocryptoviruses, all of which have worried scientists for their potential to cross over from animals to humans.

Since this was just a preliminary study, the scientists did not run experiments to see how well the viruses could infect human cells. So we don’t know if these viruses posed any threat to humans. But that’s no reason to get complacent. The scientists only studied nine primates, after all–a tiny sample of the torrent of primate bushmeat that comes into the country each year. And then there are the swarms of reptiles, mammals, and birds that come into the country as well, carrying potentially dangerous viruses that the scientists didn’t even look at. If people going through customs had to declare all the animal viruses they were bringing into the country, the list would likely be frighteningly long.

(For more information, see my book, A Planet of Viruses, my podcast interview with one of the study co-authors, Peter Daszak, and The Viral Storm by Nathan Wolfe.)

Thanks to Booklist for a late Xmas present: they put A Planet of Viruses on their Editor’s Choice 2011 list!

The book is currently available in hardback and ebook; the paperback will come out in May.

In 2011, the Loom reached its eighth birthday. Thanks to everyone who’s paid a visit or become a loyal reader in that time. With the year coming to a close, I spent a little time this week perusing the Loom’s archive, reflecting on the things that obsessed me during 2011.

More than many years, this one reminded me just how huge science is. Even if you limited yourself to the most important stories of this past year, there was just too much to keep up with. (Here’s Discover’s top 100 picks.) As a science writer, my focus is biology, but that didn’t ease my year-long case of head-spinning. The anchors that kept me from spinning away completely were the very small and the very complicated.

At the small end of the spectrum were, among other things, the bacteria that call us home. Like every year, 2011 saw outbreaks, such as the E. coli that sickened thousands in Germany. But now that we can read the genomes of these killers,  as I noted in Newsweek, we can see how chillingly fast new pathogens can evolve.

But the good germs also gained more recognition in 2011. The science of the microbiome is blooming at an astonishing pace, as you can see in the map I created for the September issue of Wired. As I got more familiar with the microbiome, it became clear to me that scientists won’t be able to handle its complexity without thinking like ecologists. I made that point in a talk this spring called “The Human Lake,” which I turned into a blog post in April. (I was delighted when it was selected as one of the best pieces of 2011 by The Browser and Longreads, and was picked to be including in the 2012 edition of Open Lab.)

The microbiome, I predict, is going to become very intimate in years to come. It’s a strangely thrilling experience to discover 53 species of bacteria living in one’s belly button, as I found out this year. In the future, doctors may check our bug types just as they check our blood types today. But all this new knowledge about the microbiome will bring us unexpected  ethical quandaries, some of which I discussed in December in the New York Times.

Bacteria may be small, but they’re positively plus-sized compared to viruses, the subject of my book A Planet of Viruses, which came out in May. (You can read excerpts in Audubon and i09.) Working on the book opened my eyes to just how abundant, diverse, and powerful viruses are–a point I tried to get across in the talks I gave in the spring. The two that I was happiest with were an interview on Science Friday on NPR, and a talk I gave at the Long Now Foundation in San Francisco. As always happens when I write a book about a fast-moving field, the science of virology offered up lots of surprises after the book came out–such as the biggest virus ever, a possible ancestor of hepatitis C in dogs, and signs of a battle between viruses and bacteria in our mouths. When the movie Contagion came out in September, I took a look in Slate at how realistic its story of a new world-wide pandemic was. I found it real enough to be very scary. And in an eerie bit of timing, this fall scientists developed a strain of bird flu that some researchers worry could make the movie a reality.

At the other end of the spectrum from bacteria and viruses is the human brain, those 100 billion neurons that make the universe aware of itself. There seems to be no end of revelatory research coming out of neuroscience and psychology. At the World Science Festival, I talked with three scientists doing extraordinary work on the mystery of sleep (you can watch the video here). In my own stories, I explored genes for language, teen brains, music in the brain, the neuroscience of smiles, how our brains make us capable of both war and peace, and the minds of Neanderthals. A lot of the pieces I wrote first appeared in the New York Times or magazines, but some of them have gotten a new lease on life. I published a new ebook in December, More Brain Cuttings, and my feature on the possibility of uploading our brains to achieve immortality was selected for The Best of American Science Writing 2011.

In 2011, it wasn’t just new science that was in the news. The nature of science was, too. Over the course of 2011, some high-profile papers came under fierce criticism, including arsenic-based life and a link between viruses and chronic fatigue syndrome. These studies prompted a debate about how science gets done in the first place, and how some of it then gets “de-discovered.” I pondered the nature of de-discovery in the New York Times in July, and the emergence of a more transparent discussion of science in Slate.

A lot of that discussion happened on Twitter. Twitter was just one of many new media that became more widespread this year. And just as scientists were getting comfortable with these channels of communication, science writers were too. I spent a fair amount of time in 2011 experimenting with different formats. On Twitter, I went after some egregiously bad science with a hashtag: #Greenfieldism. When I wasn’t on Twitter, I was often on Facebook, Tumblr, and Google+. Each medium has different strengths, I’ve found, which only emerge after playing around with it for a while. Google+ has spurred some fascinating discussions; Twitter is a fast way to spread links. I spent some time working with the folks at Radiolab this year, including the newly minted Macarthur genius Jad Abumrad. It was fascinating to see them turn spoken words into symphonies, such as this episode entitled “Patient Zero.” Another form of storytelling can be found at Story Collider, where people tell tales live in front of an audience. An invitation to be a part of a Story Collider evening led me to talk about how a trip to a war zone made me realize just how deeply science speaks to me. And at the end of the year I published Science Ink, a book born out of a blog-based obsession with science tattoos.

It was a strange year indeed when a traditional book felt like a fresh new format. And it makes me eager for the surprises waiting for us in 2012.

[Image: Wikipedia]

Eckard Wimmer makes viruses from scratch. When he first made a polio virus out of raw ingredients in 2002, some congressmen drafted a resolution to condemn him. Today, he’s making viruses that act like vaccines.

Wimmer was one of several virologists I called over the past couple days to talk about the controversy swirling around altered bird flu viruses that have the scientific community deeply worried. Their reactions are all over the board, from those who think the research shouldn’t have even been done in the first place to others who want the research published in full and replicated many times over. My report is over at Slate. It’s a debate that gets to the heart of the scientific process in the twenty-first century. Check it out.

I’ve written a few times here about the battle over a virus called XMRV, and its supposed link to chronic fatigue system. I just wanted to point this morning to a few articles by some fine writers about the latest twist: the paper that first claimed a link has been completely retracted.

Ivan Oransky in Reuters

Jon Cohen in Science

Ewen Callaway in Nature

[Image: Wikipedia]

Recently I blogged about a new strain of potentially dangerous flu that evolved during experiments in the Netherlands and Wisconsin. There I tried to counter the misconception that scientists had intentionally concocted this particular strain. Because these new flus actually evolved pretty quickly in laboratories, we now know we should take seriously the possibility that this transformation may happen in the outside world someday.

But there’s a second issue at play with this new virus: should the world get to see its genome?

As Martin Enserink reported last month, both teams of scientists have submitted their papers for publication. Normally, such a paper might include the entire genome of the new viruses. This was a touchy subject, so the papers went under review by the U.S. National Science Advisory Board for Biosecurity (NSABB).

Today, the editors at Science passed on the NSABB’s reccommendations. I’ll quote them here in full:

The National Science Advisory Board for Biosecurity (NSABB) made the following
recommendations regarding the publication of two manuscripts on highly pathogenic avian
influenza A/H5N1:

1. Neither manuscript should be published with complete data and experimental details.

2. Conclusions of the manuscripts be published but without experimental details and
mutation data that would enable replication of the experiments.

a) Text should be added describing: 1) the goals of the research, 2) the potential
benefits to public health (including informing surveillance efforts, pandemic
preparedness activities, and countermeasure development and stockpiling efforts), 3)
the risk assessments performed prior to research initiation, 4) the ongoing biosafety
oversight, containment, and occupational health measures, 5) biosecurity practices
and adherence to select agent regulation, and 6) that addressing biosafety, biosecurity,
and occupational health is part of the responsible conduct of all life sciences research.

b) The NSABB should develop a statement that explains their review process and
rationale for the recommendations. This statement will be provided to the journals to
consider for publication.

c) The USG should encourage the authors to submit a special
communication/commentary letter to the journals regarding the dual use research
issue.

In essence: “Delete the recipe and the mutations.”

The editors at Science released a statement of their own, which I’ll quote in part:

The resulting virus is sensitive to antivirals and to certain vaccine candidates and knowledge about it could well be essential for speeding the development of new treatments to combat this lethal form of influenza. The NSABB has emphasized the need to prevent the details of the research from falling into the wrong hands. We strongly support the work of the NSABB and the importance of its mission for advancing science to serve society. At the same time, however, Science has concerns about withholding potentially important public‐health information from responsible influenza researchers. Many scientists within the influenza community have a bona fide need to know the details of this research in order to protect the public, especially if they currently are working with related strains of the virus.

Science editors will be evaluating how best to proceed. Our response will be heavily dependent upon the further steps taken by the U.S. government to set forth a written, transparent plan to ensure that any information that is omitted from the publication will be provided to all those responsible scientists who request it, as part of their legitimate efforts to improve public health and safety.

Science supports the 2003 joint Statement on Scientific Publication and Security, published in Science, Nature and PNAS. The statement notes that “open publication brings benefits not only to public health but also to efforts to combat terrorism.” It further emphasizes the need to publish “manuscripts of high quality, in sufficient detail to permit reproducibility,” and it recognizes that there may be occasions when a paper “should be modified, or not be published.”

In essence, “We haven’t decided yet. It would be nice if you let us know how responsible scientists could get hold of the data.”

Vincent Racaniello, a virologist at Columbia University, thinks taking this path is a bad idea. Here’s how he put it to me when I sent him the statements:

It doesn’t make any sense to publish Fouchier’s paper without complete data and experimental details. The point of a science paper is to enable others to duplicate the findings. Are we going to set a new precedent, where security matters override the reason for publication? This is setting a very dangerous precedent for virology and biological sciences in general.

I disagree with the NSABB recommendations, because they have no scientific basis…one cannot conclude that the mutations selected by Fouchier [the head of the Dutch research team] will have effects on transmission of the virus among humans. I understand that if you publish the plans for a nuclear weapon, that may enable a terrorist to make one, but the Foucher finding doesn’t enable anything except more experiments. And that is why the paper should be published – to allow virologists to extend his findings and determine what controls transmission of H5N1 viruses. Often the best experiments are done by scientific unknowns who take an interest in a problem and apply a fresh view. If you restrict dissemination of this information, you are limiting our eventual understanding of the problem.

Update: Looks like Racaniello’s concerns have fallen upon deaf ears. Martin Enserink reports that the virus researchers have decided to redact the contested parts of the papers, which are being considered by Science and Nature.

There are 100 trillion microbes that live in your body. Do you own them? Do they deserve the same protections as your own genes and cells? If someone genetically alters a microbe and claims that if you swallow it, it will let you lose weight, should that living germ be regulated as a drug?

These are a few of the questions I mull in a piece that appears in the Sunday Review section of today’s New York Times. I’ve been writing a lot about the microbial world for a few years now, but only recently did I encounter a group of bioethicists who are now pondering what sort of ground rules we should set up to govern science and medicine as we gain understanding and power over the microbiome. Check it out.

If you’re interested in reading more about all this, here are a few new papers (some free, some behind paywalls).

The Human Microbiome Project: lessons from human genomics: Trends in Microbiology (in press)

“Who owns your poop?”: insights regarding the intersection of human microbiome research and the ELSI aspects of biobanking and related studies, Kieran O’Doherty, BMC Medical Genomics 4 (1), (07 Oct 2011) info:doi/10.1186/1755-8794-4-72

Community Health Care: Therapeutic Opportunities in the Human Microbiome Justin Sonnenburg and Michael Fischbach, Science Translational Medicine 3 (78), April 13, 2011 info:doi/10.1126/scitranslmed.3001626

There will also be a book coming out next year edited by Rosamond Rhodes of Mount Sinai Medical School, but it’s not on the radar just yet. For now, here’s a powerpoint of a recent presentation from her research group (pdf)

[Image: Andrea Wan for the New York Times]

When it comes to viruses, we humans like to pretend we know much more than we really do. It’s understandable. The influenza virus, for example, has only ten genes. It is just a shell that delivers genes and proteins into a host cell, where it hacks the biochemistry to manufacture more viruses. It seems like such an easy biological problem to solve.

Yet the flu and other viruses hide a complexity which virologists have only partly uncovered. The idea that someone could intentionally design a super-lethal virus from scatch–as plausible as it may seem–is, for now, a delusion.

If you’ve been following the news this past week, you may think I’ve just been proven wrong. Reports have surfaced about two teams of scientists producing flu viruses that could potentially kill millions if they escaped from the labs. The scientists have the viruses locked up tight for now, and government officials are debating whether they can publish their results. (New Scientist and Science have excellent reports.)

So is this evidence that scientists have become viral Frankensteins, who can engineer pathogens at will? Hardly.

The new research is part of a long-running struggle to understand how new flu strains arise. It’s clear that all flu viruses that infect humans ultimately evolved from viruses that infect birds. From time to time, people can pick up these viruses, which infect their airway. Depending on the strain, bird flu may be harmless or lethal to humans. But for the most part, it can’t get from one human to another. It’s too well adapted for life in birds.

On rare occasion, a bird flu does manage to adapt to humans. It may experience natural selection, it may pick up some genes from human flu viruses, or both. Scientists are still trying to figure out what it takes for a flu virus to make this transition. It’s an important question, not just as a matter of fundamental biology but as a matter of global health. When new bird flus jump to humans, we lack immune defenses against them, and they can thus cause worldwide pandemics.

Flu experts have had their eye on one strain of bird flu in particular for a while now: H5N1. It’s proven extraordinarily lethal, and yet, since it first came to light in 1997, it hasn’t managed to make the big leap and start spreading from person to person. If you get H5N1, you’re in big trouble. But not many people get it. Yet.

Does this mean that H5N1 just doesn’t have what it takes to become the next great pandemic? Or does it mean the virus simply hasn’t evolved the right recipe yet?

Scientists have tried to answer this question by tinkering with the virus. Instead of trying to make a virus that spreads among people, they infected ferrets, which turn out to have much the same experience with the flu as we humans do. In April, CDC scientists published the latest of these studies. They focused their attention on a protein called hemagglutinin, which flu viruses use to get into host cells. Based on earlier experiments, the CDC scientists reasoned that the right tweak to the structure of hemagglutinin in H5N1 could switch it from binding strongly to bird cells to mammal cells.

But their rational tweaks failed. They concluded that there was a lot more to becoming a human flu that we don’t yet understand.

The studies that have now hit the news have succeeded where other experiments have failed. The difference is that instead of trying rational tweaks, the scientists sat back and let evolution do the tweaking.

According to the news reports, the scientists used a tried-and-true method known as serial passage. You infect an animal. It gets sick. You wait for the virus to replicate inside its animal host–as new mutants arise and natural selection favors some mutants over others–and then take some viruses from the sick animal and infect a healthy one. You repeat this, moving the virus from host to host.

Interesting things can happen when you let viruses evolve under these conditions. Natural selection can produce viruses with many new mutations, which together let them reproduce faster in the lab than their ancestors. And those viruses, in some cases, can be a lot more dangerous than their ancestors.

Back in 2007, for example, a virologist named Kanta Subbarao and her colleagues transformed the SARS virus this way. SARS evolved from a bat virus, crossing over into humans in 2003. It killed over 900 people before it mysteriously disappeared. Subbarao wanted to find a way to study SARS in lab animals, such as mice. Mice normally don’t get sick from human SARS viruses, though, even though the virus can replicate at a low rate inside them. Even when mice are genetically engineered so that they can’t develop an immune system, SARS can’t harm them.

So Subbarao and her colleagues that instead of changing the mice, they’d change the virus. They inoculated mice with the SARS virus, gave it a chance to replicate inside them, and then isolated the new viruses to infect new mice.

Over the course of just 15 passages, it changed from a harmless virus into a fatal one. One sniff of SARS was now enough to kill a mouse.

As Martin Enserink reports in Science, the new experiments on bird flu were similarly effective. They turned H5N1 into a ferret flu in just 10 generations. By the time the scientists were done, they no longer had to ferry the flu from one ferret to the next. A healthy ferret just had to be placed near a sick one; the virus could travel through the air. When they examined the new strain, they discovered five mutations in two genes. All five mutations have been found in natural H5N1 viruses–just not all in one virus.

A mammal-ready flu virus was beyond human reason, in other words, but it was fairly easy for evolution to find, given the right condtions. That suggests that H5N1 may not have far to evolve to make us its host. Of course, a serial passage experiment is not identical to the flu’s natural world, where it circulates among millions of birds and sometimes encounters people. But it’s disturbingly close.

And if it’s so easy for mutations to turn H5N1 into a human flu, the experimental viruses have a lot to tell us about what we may be facing in the future. There’s no point in condemning the scientists for tampering with nature. They were watching nature do what it does disturbingly well.

[Update: The excellent podcast This Week in Virology discusses the new research. They think the hype to reality ratio is very high.]

[Image: Virology Blog]