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started to bubble up in September, when Ron Fouchier of the Erasmus Medical Center in Rotterdam described some of his unpublished results at a scientific meeting in Malta.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 .]

Over on Facebook, David Hillis, an evolutionary biologist at the University of Texas, took up my question as to whether anyone can define life in three words. His short answer was no, but his long answer, which I’ve stitched together here from a series of comments he wrote, was very interesting (links are mine):

Like all historical entities (including other biological taxa), it is only sensible to “define” Life ostensively (by pointing to it, noting when and where it began, and following its lineages from there) rather than intensionally (using a list of characteristics). This applies to the taxon we call Life (hence capitalized, as a formal name). You could define a class concept called life (not a formal taxon), but then that concept would clearly differ from person to person (whereas it is much less problematic to note examples of the taxon Life). So, I’d say that I can point to and circumscribe Life, and that it the appropriate way to “define” any biological taxon. A list of its unique characteristics is then a diagnosis, rather than a definition. So, I’d argue that any intensional definition of Life is illogical (does not recognize the nature of Life), no matter how many words are used.

Defining Life (the taxon) is like defining other particular historical entities. We don’t “define” Carl Zimmer or the United States of America by listing out their attributes. Instead, we point to their origin and history. The same should be true for Life. If we ever discover a Life2, we’ll have a new origin and history to point to.

The question people actually want to ask is “Are there entities in the universe that are similar to the Life we know about here on Earth?” The answer, of course, depends on what people mean by the arbitrary meaning of “similar”. One person might answer “I mean ‘self-replicating with variations’.” Then, the answer is yes: humans have created imperfectly self-replicating systems (“artificial life”) here on Earth. But then someone else says “But that is not what I meant by similar…I meant that they had to have metabolism and cellular structure and a nucelic-acid-based genetic system.” OK, then we have to keep looking to find something that similar. But then someone else says “But that’s pretty arbitrary…I’d still consider it alive if it didn’t have cellular structure.” Exactly…it is indeed arbitrary to argue over how similar something has to be to consider it “similar” to Life. So, in the end, we can ostensively define Life (by referencing its origin and history), and we can do the same for other historical entities that some people might also want to say are alive, but there can be no simple “right” answer that will satisfy everyone about which entities should be considered alive, because we all emphasize different characteristics in defining an arbitrary class concept of “life”.

We are all sure we know what life is, but if you try to actually define it, things get tricky fast. I wrote a feature about the scientific struggle to define life in 2007 for Seed, and I’ve been keeping tabs on the evolution of this metaphysical quandary ever since. I was particularly intrigued to discover recently that one scientist thinks he can define life–and do so in just three words. I’ve written an essay about his short and sweet definition for the web magazine Txchnologist. Check it out.

On Friday, as the E. coli outbreak gained horrific speed in Germany, Newsweek asked me to write about how this epidemic came to be. Scientists still have a lot to figure out about it, but some things are clear–in particular, that the bacteria have great scope for evolution into new deadly strains, thanks in part to the shuttling of viruses between them. (In my book Microcosm, I explain how this is true not just for E. coli, but for much of life.) My piece appears in the new issue of Newsweek, which you can read online here. (One late-breaking piece of news that didn’t make it in, by the way, is the finding yesterday that the new outbreak appears to have come from bean sprouts.)

While I was working on my Newsweek piece, a reporter for the BBC called me up for an article on the good side of E. coli. I explained how much of how we understand about life itself came out of research on this typically harmless bug, and that the biotechnology industry was build upon its biology. That piece came out over the weekend. Check it out.

[Image: glass microbe by Luke Jerram]

If you live in central Connecticut, please consider coming to my public lecture tomorrow (Wednesday 4/12). It’s entitled, “Synthetic Biology: Playing God or Harnessing Nature?” The talk is sponsored by the Connecticut Association of Biology Teachers, the Connecticut Valley Branch of the American Society for Microbiology, and Manchester Community College.

Here are the details:

Where: Manchester Community College, Great Path Academy Building, Community Commons. (Here are directions and maps.)

When: 5:30 pm, Wednesday, April 12

More information here.

Last year I wrote about how Craig Venter and his colleagues had inscribed a passage from James Joyce into the genome of a synthetic microbe. The line, “To live, to err, to fall, to triumph, to recreate life out of life,” was certainly apropos, but it was also ironic, since it is now being defaced as Venter’s microbes multiply and mutate.

Turns out there’s an even weirder twist on this story. Reporting from SXSW, David Ewalt writes about a talk Venter just gave. Venter recounted how, after the news of the synthetic microbe hit, he got a cease-and-desist letter from the Joyce estate. Apparently, the estate claimed he should have asked permission before copying the language. Venter claimed fair use.

Man, do I wish this would go to court! Imagine the legal arguments. I wonder what would happen if the court found in the Joyce estate’s favor. Would Venter have to pay for every time his microbes multiplied? Millions of little acts of copyright infringement?

[Update: Looks like it wasn't actually a cease-and-desist letter the Joyce estate sent--more an expression of disappointment. Ah, life's grand game of telephone. Joyce would have loved it. After all, he was the sort of novelist who'd write :

"What has she in the bag? A misbirth with a trailing navelcord, hushed in ruddy wool. The cords of all link back, strandentwining cable of all flesh. That is why mystic monks. Will you be as gods? Gaze in your omphalos. Hello. Kinch here. Put me on to Edenville. Aleph, alpha: nought, nought, one. Spouse and helpmate of Adam Kadmon: Heva, naked Eve. She had no navel. Gaze. Belly without blemish, bulging big, a buckler of taut vellum, no, whiteheaped corn, orient and immortal, standing from everlasting to everlasting"]

Last month I wrote a piece for the New York Times about what ten scientists are looking forward to in 2011. One of the scientists, Rob Carlson, saw garage stem-cell research in our near future:

“It seems pretty likely within this year someone will show how to go from an adult peripheral blood draw to pluripotent stem cells. It means anyone who wants to try to make stem cells will be able to give it a whirl.”

Carlson took to his own blog to write at more length about what exactly he meant. For one thing, stem cell biohackers may want to think twice before sticking stem cells in their own bodies. They could end up with what Carlson calls DIY tumors. Check it out.

Two of my favorite bloggers, John Hawks and Christina Agapakis, talk about the big genome news of recent weeks on Bloggingheads. Gets technical, but in a good way!

I’ve got some public face time coming up:

Tuesday, May 25, 5:30 pm: In San Diego, I’ll be talking at the American Society for Microbiology. I was asked to speak at the President’s Forum, “Tell the Story of Science.” My own talk is, “Newspapers, Blogs, And Other Vectors: Infecting Minds With Science In the Age of New Media.”

Random House will be kindly providing copies of Microcosm for sale at the meeting. I will spend some time signing them all when I get to the conference Monday. The books will be available at the American Society for Microbiology Press Booth. (I’ll update this post when I know exactly where the booth is located.)

I’ll also plan on hanging out at the booth at some point on Wednesday, hoping that I can meet face to face with some of the Loom’s microbiologist readers. (Again, I’ll update this post about exactly when I’ll be there once I get to the meeting.)

Thursday, June 3, 7 pm: The World Science Festival returns to New York for its third year, and I’m delighted to enter my third year of moderating panels for them. I’ll be part of “Modern MacGyvers,” a gathering of innovative thinkers who are designing solar panels for camels, cook stoves that could save millions of lives, and other important inventions.

I may be asked to moderate other panels; if so, I’ll update this post accordingly. I will definitely be going to some other sessions as an audience member: the line-up looks great.

Thursday June 3, 8 pm and 10 pm: The Science Channel is airing, “Creating Synthetic Life,” a show about Craig Venter’s new hand-made cell. The producers asked me to talk about the research Craig Venter and his team have been carrying out for the past fifteen years on the path to creating artificial life. At the time they interviewed me (a few weeks ago), I knew there was some big news coming down the pike, but wasn’t able to talk about the particulars. So I expect that I’ll turn up on the show speaking in hazy generalities set in the future tense. Feel free to set your TV on mute when I show up. But based on the previews, I think the rest of the show is worth checking out.

This old English major’s heart is warmed by the news that the new synthetic cell carries a line from James Joyce, inscribed in its DNA: “To live, to err, to fall, to triumph, to recreate life out of life.”

What would Joyce have thought if someone had told him that one day the synthesized genome of a goat pathogen would carry his words? I would hope that whoever told him would make sure that he did not think this moment marked his literary immortality. In fact, his deathless prose is probably being desecrated by the relentless erosion of evolution right now.

The scientists who produced the new synthetic cell copied the genome of a microbe, letter for letter, and then inserted the synthetic version into a host cell. To determine that their experiment worked, they needed a way to tell the genomes of their synthetic cells from the natural genomes that were their model. So they inserted “watermarks” into the artificial genome. These sequences of DNA (which spelled out the work of Joyce and others through the genetic code) sit in non-coding regions of the microbe’s DNA. As a result, these watermarks cannot disrupt any essential protein-coding genes or stretches of DNA that are vital for switching genes on and off.

It turns out that the genome of the synthetic cell is not identical to its original, even if you ignore the watermarks. Mutations slipped into its sequence during its synthesis. Yet those mutations caused no harm to the microbe, presumably because they didn’t disrupt an essential function encoded in its DNA. Once the synthetic cell came to life and began to grow and divide, it copied its entire DNA, including Joyce’s words. But as lovely as those words may be, and as important as they may have been to the scientists during their experiment, they mean nothing to the microbe. Every time an organism replicates, each spot in its DNA has a tiny chance of mutating.

In the growing colony of synthetic cells, now numbering in the billions, it’s almost certain that Joyce’s watermark has already been defaced by a mutation. The bacteria that carry these degraded versions of Joyce presumably do not suffer from these mutations, since the watermarks don’t matter to them anyway. So they can keep replicating.By contrast, the DNA in the really useful parts of their genome is changing very little over the generations, thanks to selection.

Inserting Joyce into the first synthetic cell was certainly a kind gesture, but not a timeless memorial. It would be fascinating to go back to the synthetic cell colony in a few years and sequence Joyce’s line again. I’d bet that it won’t even be recognizable anymore.

The fate of Joyce’s DNA points up something important about this project. There have been lots of headlines over the past day about how the scientists who made this cell were playing God. Yet our power, even over synthetic cells, is limited. Once this new cell came into existence, it started changing through evolution, slipping away from its original form. In fact, evolution is the great enemy of all scientists who want to use synthetic biology to supply us with medicine, fuel, and other valuable things. Once they engineer a microbe, they start to lose control of their handiwork. Life takes its own course from there. It is life, ultimately, that recreates life from life.

Craig Venter has taken yet another step towards his goal of creating synthetic life forms. He’s synthesized the genome of a microbe and then implanted that piece of DNA into a DNA-free cell of another species. And that…that thing…can grow and divide. It’s hard to say whether this is “life from scratch,” because the boundary between such a thing and ordinary life (and non-life) is actually blurry. For example, you could say that this is still a nature hybrid, because its DNA is based on the sequence of an existing species of bacteria. If Venter made up a sequence from scratch, maybe we’d have crossed to a new terrain.

Anyway–this news just hit the wires thanks to an embargo break, so I don’t have time to go into more detail. Joe Palca at NPR has posted his article on the subject. For background, please check out these stories I’ve written about this general area of research:

Tinker, Tailor: Can Venter Stitch Together A Genome From Scratch?

The Meaning of Life

The Six Most Important Experiments In The World

Artificial Life? Old News.

The High-Tech Search For A Cleaner Biofuel Alternative

On the Origin of Tomorrow

My Bloggingheads interview with Venter

Update: The scientists are in a live press conference that started a 1 pm.

Here’s a talk I just gave on Big Think–about viruses, synthetic biology, and tapeworms that carry my name. The sound quality isn’t as good as I’d like, but I hope the words make up for it.