Irven DeVore: October 7, 1934 – September 23, 2014 [Greg Laden's Blog]

I heard yesterday that my friend and former advisor Irven DeVore died. He was important, amazing, charming, difficult, harsh, brilliant, fun, annoying. My relationship to him as an advisee and a friend was complex, important to me for many years, and formative. For those who don’t know he was instrumental in developing several subfields of anthropology, including behavioral biology, primate behavioral studies, hunter-gatherer research, and even ethnoarchaeology.

He was a cultural anthropologist who realized during his first field season that a) he was not cut out to be a cultural anthropologist and b) most of the other cultural anthropologists were not either. Soon after he became Washburn’s student and independently invented the field study of complex social behavior in primates (though some others were heading in that direction at the same time), producing his famous work on the baboons of Kenya’s Nairobi National Park. For many years, what students learned about primate behavior, they learned from that work.

Later he and Richard Lee, along with John Yellen, Alison Brooks, Henry Harpending, and others started up the study of Ju/’hoansi Bushmen along the Namibian/Botswana border. One of the outcomes of that work was the famous Werner Gren conference and volume called “Man the Hunter.” That volume has two roles in the history of anthropology. First, it launched modern forager studies. Second, it became one of the more maligned books in the field of Anthropology. I have yet to meet a single person who has a strong criticism of that book that is not based on having not read it.

For many years, much of what students learned about human foragers, they learned from that work.

DeVore supported the rise of Sociobiology but his version of it was nuanced and investigatory, not dogmatic and oversimplified as the subfield eventually came to be. He fought with Lewontin though they essentially agreed on salient points. He launched a number of outstanding researchers mainly in primate studies, and well understood the problem of sexism in the field. So, many of his proteges were women, and many of those are now household names (if you live in a house of anthropologists). Barbara Smutts, Nadine Peacock, and Sarah Hrdy for example. Karen Strier holds the Irv Devore Chair at Madison. Eventually he hooked up with Bob Trivers, who was busy re-inventing the newly invented Behavioral Biology. Cosmides and Tooby were his students as well and he was their champion. He also supported the work of Daly and Wilson.

For years he taught one or another version of “Sex”, the nickname for his course on human behavioral biology. Imagine a course taught for decades, a required course with 500 students a year, at a small but elite college like Harvard. How many students learned what they learned about human behavior from DeVore? Those of us who were involved in “Sex” saw this now and then: a Hollywood movie with one of Irv’s examples from the animal world worked into the script, or a novel with such a reference, etc. … yup, the writer or director was one of those students.

One of my first meetings with DeVore was at the home of David Maybury-Lewis, down the street from Irv’s house. DeVore pulled me aside and assigned me to be the head teaching fellow for that course. I was horrified. He forced me into the job. I did it poorly, since I was an archaeologist with virtually zero background in the field and most of the other TA’s (about eight of them) were advanced PhD students or post docs. Eventually I learned the ropes but I think I managed to avoid being head TA ever again (Jay Phelan, my Suaboya, was not so lucky, that became his job for many years). I later served as Irv’s understudy, when he was getting a series of brain surgeries. I waited in the wings to step onto the lecture hall floor in case he succumbed. That never happened, but I did take a couple of the lectures while he was in hospital. I gave his lectures as he would have given them, including jokes and personal stories (but with the personal stories in third person). When he returned he re-told all the jokes and personal stories in case I had messed them up. Like I said, he could be annoying. But I digress.

By the time I was on DeVore’s teaching staff, the Harvard Ituri Project, started by Bob Bailey and Peter Ellison, was well underway and I was sent off to do my PhD fieldwork there. That project was also championed by DeVore, he was in the field there for a while.

DeVore had a major impact on Harvard’s Anthropology department. He was mainly responsible for the division of that department into autonomous wings, which eventually led to the separation of the biological anthropology wing from the rest of the Department. This is important because the entire field in the US was under similar pressures. When Harvard “split” into wings, all the other departments were free to ask themselves if they should too. I remember the very famous head of a very major anthro department visiting to see what a split department looked like. Over subsequent years some split, some entrenched.

DeVore was instrumental in shaping the faculty of the whole department, but mainly the biological anthropology wing. It is fair to say that David Pilbeam, Peter Ellison, and Richard Wrangham are on that faculty in large part because of Irv.

As I say, my relationship with Irv was complicated, but it was good. I was his last PhD student, though he had a hand in the careers of other later students. I was his confidant (one among others) and he was mine. We often met up at the end of the day in his office to debrief, he’d have a drink. He kept his scotch in a fake book flask. Then we would leave together, and he’d drive me home, or I’d drive him home, or we’d go to his place to hang out.

Of all of these things that happened in his career, the research and the effects on the field of Anthropology, his wife Nancy DeVore was as much a part as he. Irv’s deployment of his advisory duties often involved Nancy. Nancy taught me a lot about writing and editing, for example. Over the last few years, his daughter, Claire, has taken on the difficult burden of caring for a difficult person having a difficult time. Claire is as unique and potent a person as her father. I love both of you, Nancy and Claire.

I’ll probably say more at another time. That’s all I’ve got now.

________________

Photo from AnthroPhoto

When Buying Fountain Pens, Splurging (a Little) Is Totally Worth It

Josh Valcarcel/WIRED

What do you get for your money? That’s the question everyone looking to buy a piece of tech asks themselves. It also happens to be the question this recurring feature will try to answer. Is it worth spending extra on high-end gear, or do you get what you need with cheaper models? Every month, we’ll look at some of the cheapest and most expensive products in a given category, testing each to see what their limits are and help you figure out when you can cheap it out, and when to plunk down some extra cash to get what you need.

Hi/Low: Fountain Pens

The pen may be mightier than the sword, but choosing the right one can still be painful. Not only do you have a daunting number of styles to choose from, there are also things like the nib, ink, and other variables to consider. Even when you narrow down the field to just fountain pens, there are a bewildering number of choices available, ranging from cheap and cheerful to stupidly expensive status symbols that cost more than a small car. So is there a noticeable difference between the two?

I decided to find out by trying a $25 Lamy Vista and a moderately expensive ($125) Delta Serena. After filling both with high-quality ink (Noodler’s Heart of Darkness), I set out to write my memoirs using both pens. Many pages later, I was familiar with both pens and how it feels to write many pages of invective ranting with them.

This is the first time I’ve used a fountain pen for several years, and I had forgotten how nice the feel and scratch-scratch noise of a pen on paper can be. Writing by hand should be a pleasurable experience, and a decent fountain pen enhances this, with a well-balanced weight and a nib that glides smoothly over the paper. However, I am also old enough that I was taught to write with a fountain pen, an education that many younger writers won’t have. It takes practice: writing with a fountain pen is very different to using a ballpoint or gel pen as you have to be more in control of the angle and stroke of the nib on the page. There are plenty of great guides to learning the proper technique, but I would particularly recommend the handwriting and fountain pen sections of Reddit, both of which are populated by helpful pen enthusiasts.

A Pen in the Hand

Josh Valcarcel/WIRED

Although they are quite similar in design, the two pens feel quite different in the hand. The Lamy Vista is unapologetically plastic, from the clear plastic exterior to the clip on the lid. That’s not a bad thing. The plastic feels comfortable in the hand. The long neck of the pen—the part behind the nib that you hold—has two indented sections that the thumb and index finger naturally fall into. Similarly, the barrel—the part that fits over the ink cartridge—has two flat sides that stop the pen from rolling around on a desk top. All of these parts are made of clear ABS plastic: The only metal parts are the nib and the paperclip-styled top. However well-styled the plastic is, it still feels like plastic, and I found my grip on the pen did get slightly slippery when writing on hot and humid days. In the rush to get down a particularly well-crafted insult on paper, I did find the pen slipping slightly sometimes.

The Delta Serena, by contrast, is more of a classic fountain pen. It has a heavier, more solid construction than the Lamy, and feels more substantial. Delta claims that each pen is hand-carved from a solid block of resin, and it certainly feels like a precision instrument in the hand, with a better balance (the weight is centered in the middle) that makes it easier to hold for longer periods. There are no indentations on the neck, though, so you have to check your grip on the narrow neck and make sure the nib is flat against the paper before you start writing. The narrow neck also encourages a lighter grip, which makes for more fluid writing. There are a lot of nice design touches that make it feel classier than the Lamy, including a screw-on lid and top (so it won’t pop off accidentally) and a much stronger seal in the cover of the ink reservoir: when the lid is on and screwed down, it feels like you’d have to crush most of the pen before it leaked.

Ink on the Page

The Lamy uses standard ink cartridges, but a cheap converter is available that adds a piston draw ink reservoir. The Delta Serena comes with an included piston reservoir, but can also use cartridges if you prefer. Both models are easy to fill: Remove the end of the pen, dunk the nib in the ink and turn the screw top on the reservoir to lift the piston and suck it up.

Josh Valcarcel/WIRED

I tried both pens with a fine tip nib, but they are available in other sizes too. That’s one of the joys of fountain pens: if you don’t like the stroke of the pen, you can swap the nib out, or even (god forbid) replace it with a ballpoint mechanism. The nibs are proprietary to the manufacturer, but there is an active market in third party nibs and parts. Both pens had a similar nib size, but the Delta produced a somewhat heavier stroke with more ink, which does mean that I tended to write faster. The Lamy produced a thinner, lighter line with the same speed and pressure.

These two pens show different approaches to designing a fountain pen. The Lamy Vista is about simplicity, about making a pen that is as cheap, robust and simple as possible. It’s a fountain pen for students and those who write a lot, but don’t want to spend much. The Delta Serena is a pen for the more classic fountain pen user, the one who cares more about the refined touches that make a fountain pen unique.

Why Bother With a Fountain Pen?

Cynics will dismiss using a fountain pen these days as a needless hipsterism, a tacky bit of retro nostalgia that serves no real purpose. I disagree. A good fountain pen is a piece of precision engineering and design, and will serve you well for many years. Using a fountain pen is about making a deliberate choice to buy something that you can use repeatedly, rather than something you use once and loose. If you want to write casually, get a Bic disposable and throw it away when you’re done. But if you want to have something that looks cool and is a pleasure to use, get a fountain pen.

However, there are limits. Expensive fountain pens can be more about status than usability. If I spent $935 on a Mont Blanc Meisterstuck 90 Years 149, I’d be afraid to take it out of the house. For me, the Delta Serena is the best pick here: it looks great, feels great and writes well, with a more comfortable and smooth writing experience than the Lamy. I’d be sad if I lost it, but at $110, I wouldn’t feel like I had lost a family heirloom.

Vizio’s Affordable 4K TVs Are Your Perfect Stepping Stone to Ultra HD

Vizio

When they were introduced at CES, Vizio’s P-Series LCD sets did something most other LCD TVs at the show didn’t: They made buying a 4K set seem enticing and affordable. Starting at $1,000 for a 50-inch panel, the Ultra HD resolution (3,840 x 2,160) wasn’t the only thing that made the new TVs stand out.

The other perks included full-array backlight panels with local dimming. That kind of setup is normally only found on the highest of the high-end LCD sets, but Vizio has been adding these once-expensive features to all its TVs in 2014.

The 70-inch P-Series set has 72 local-dimming zones, while the rest of the models have 64 zones. Each of the sets also has a technology called Active Pixel Tuning that helps eliminate light bleed even further. The benefits of both features will be plain to see in terms of sharp contrast: Granular control over brightness combined with the balanced, bright lighting of a full-array LED should help the P-series approach the near-perfect picture quality that OLED delivers.

The picture quality for the price will also make these sets an excellent choice for anyone who isn’t quite sold on an Ultra HD upgrade. The backlight technology alone will help produce an excellent 1080p picture, and Vizio says its sets will also upscale high-definition video to “near Ultra HD” resolution. The TVs support 4K video at up to 60fps via a suite of smart TV options, which include streaming Netflix, Amazon, and other sources over 802.11ac Wi-Fi.

Hardware-wise, the P-series continues Vizio’s design trend of thinning out the bezel to bestow a wall-to-wall picture effect upon your eyeballs. The new sets have a native refresh rate of 240Hz, as well as a simulated “Clear Action Rate” of 960Hz if you’re really into the soap-opera effect. To handle all that motion processing and 4K content, the P-series is driven by six processing cores: A quad-core GPU and a dual-core CPU.

Although prices and sizes for the P-series TVs were announced way back in January, we’ve been waiting for them to actually become available. It’ll be any day now, and you can preorder them on Vizio’s site today. The 50-inch P-series set will sell for $1,000, the 55-incher will go for $1,400, the 60-incher is priced at $1,700, the 65-inch model will cost $2,200, and the 70-incher will sell for $2,500. More good news: None of them are curved.

Duh: Of Course the iPhone 6 Plus Can Bend in Your Pocket

Josh Valcarcel/WIRED

Some iPhone 6 Plus users are discovering their handsets do something Apple isn’t advertising: Bending. Yes, a few phablets are bowing slightly after being kept in back pockets and then sat upon.

You could say it’s a pocket-sized controversy, and you’d (mostly) be right. Considering the device is just over a quarter-inch thick and made largely of aluminum, a flexible metal, the fact this jumbo iPhone will bend when great pressure is placed on it for extended periods is a bit of a well, duh . It’s something that happens, albeit rarely, to iPhone 5s and iPad owners.

If you do manage to torque your spendy, bendy new iPhone 6 Plus, there could be consequences. Batteries and displays are not meant to bend, unless they’re designed to do so from the outset, like the curved LG G Flex smartphone (which even has special curved batteries to accommodate its form factor).

“LCDs are made with delicate front and back glass panels. Even if they don’t break, putting mechanical stress on them could affect the critical alignment between the front and back glass layers, which would then significantly affect the display performance and image quality,” said Raymond Soneira, a display expert and president of DisplayMate. Soneira recently published a detailed analysis of the iPhone 6 and 6 Plus’ displays compared to other leading mobile displays on the market.

If your display panel gets damaged, you could experience issues like brightness irregularities at the edge of the screen, dead pixels, or colors striping across the screen.

In particular, lithium-ion batteries cannot withstand the stress of repeated bendings and will explode if you say, bent your iPhone back and forth over and over and over again. One kid did just that in 2011. But iFixit’s Kyle Wiens says iPhone 6 Plus owners shouldn’t have to worry about this because there’s a metal plate between the display and the battery.

Soneira agrees, saying that for minor stresses, the phone’s display assembly should hold up just fine thanks to its metal rear casing. Third-party device insurer SquareTrade did find the iPhone 6 and 6 Plus are Apple’s most durable iPhones yet. But, as with dropping any phone, sometimes even a minor fall can create the wrong kind of stress.

If you insist on sitting on your iPhone 6 Plus, Soneira recommends placing it in your pocket with its back facing your backside. “The cover glass [on the display] should do a good job of protecting the frontside from whatever you are sitting on,” Soneira says. But considering your new phone cost at least $300, why take the chance? Take it out of your pocket before sitting down, or invest in a new blazer or jacket that has a dedicated smartphone pocket.

The Ghost of Invention: A Visit to Bell Labs

Curiously, the conversion from dog into cat is dealt with in an oblique manner by my next Alcatel-Lucent interviewee, Marcus Weldon. Weldon is Corporate Chief Technology Officer and has a large office, which he has made some commitment to personalizing with a large magnetic spinning globe that works bravely to combat the beige paint and sun-faded blond hardwoods and oatmeal carpeting. His dryerase whiteboard panels are the cleanest in the building, showing no ghosts at all of meetings past.

While many of us have special skills and talents, Weldon’s is that he’s scary smart. As his bio, pillaged directly from the Alcatel-Lucent website, proves, this guy really knows his stuff:

[Weldon holds] a Ph.D. degree in Physical Chemistry from Harvard University. He joined AT&T Bell Labs in 1995, winning several scientific and engineering society awards for his work on electronics and optical materials. In 2000, Dr. Weldon started work on fiber-based Broadband Access technologies and, in 2005, became the CTO for Broadband Solutions business group in Lucent Technologies, with responsibility for wireline Access Networks and IPTV. He was subsequently appointed as CTO of the Fixed Access Division and the Wireline Networks Product Division in Alcatel-Lucent following the merger of Alcatel and Lucent in December 2006, with responsibility for xDSL and FTTH, IPTV, Home Networking and IMS.

The two of us quickly fall into a discussion about modern communications. Weldon points out that, in 1995, “Nobody in Bell Labs used the Internet. People used UNIX command-line addresses.” UNIX is a computer operating system invented by Bell Labs in 1969. “I’m surprised by how quickly the Internet became huge, and the amount of personal trivia people share with each other comes as a total surprise.”

It is in this massive amount of trivia that Weldon sees the future of communications technology. “The future is not so much about delivering information (AI) or organizing it (Google), but about managing the rising tide of information so that it doesn’t drown us. Nobody wants to drink water from a fire hose. I need to be interacting with a set of machines that will allow me to optimize my life. We also need to make the physical world and the virtual world interact—as what happens playing with Kinect and Wii.” He spins the globe. “I think that the future is in ‘immersive communication.’ It’s about abstracting yourself into a space of your own choosing, and it ought to resemble Obi-Wan Kenobi visiting you in a meeting in 3D. And the future is a machine that learns you. It’s a machine that knows all of your preferences.”

A machine becoming my “parallel me” certainly does not strike me as being too crazy. Most of us leave scads of digital traces behind us almost every second of our lives. If your phone has a GPS connected to a single downloaded app, then your presence on earth can be perpetually recorded. A few years back one company announced an ambient function that works by recording all of the sounds as heard through your laptop’s microphone. Whenever there is a sound that can be interpreted as a word, Google will do so, effectively transforming your entire life into a searchable document.

Scary.

I used to collect high-school yearbooks; the faces in them often trigger interesting ideas for characters and plot twists. I’m realizing that the day is soon approaching when your old yearbook will be scanned and your teen self will be searchable forever, bad hair, zits and all—facial recognition software is getting that good. In 2001 a friend and I wrote a script for a movie called Doppelgangers. Its premise is that the villain uses secret facial recognition software to locate his look-alike and, of course, murder ensues. A studio note came back saying, “Implausible.” A decade later, I think not.

Just yesterday, someone pointed out to me that I have written well over a thousand messages on Twitter. When multiplied by Twitter’s 140-character limit, this is basically a novel of some sort, a new genre impossible to imagine even a decade ago—neither blog, nor diary, nor bulletin board, nor… well, that’s the whole issue: because it’s new, it’s not like anything else.

Last night I was looking at a map of the world circa 1500 and most of the west coast of North America didn’t exist. As a species, all of these new realities are taking us into vast unmapped continents, the New World.

Weldon does, in the end, come back to the Alcatel-Lucent maxim that research must be tethered to some dimension of utility or end product. “AT&T’s monopolistic history meant there was never any time pressure. But now there is. Our situation hasn’t reached the point where we say, ‘Good enough and ready.’ You can’t just be hacking things together, seeing what works, and then creating iterations from there. But with new products you also don’t want to be in the position of ‘working versus perfect and too late.’ But no, it’s not like it used to be. We now have an accelerated delivery paradigm.”

When I ask if a huge conglomerate like Alcatel-Lucent can be nimble enough to meet the requirements of the times, Weldon says, “We’re making progress at turning the cruise liner. We’re not a speedboat, not yet, and while we’re good at technology, we have to grow better at servicing the technology.” This is a large new trend in technology: people who make the stuff now have to service the stuff.

Corporations can feel swamped by new inventions, just as people do. If anything defines the times we live in, it is surely that we all feel the need to take a one or two-year break from any more new technologies being thrown our way. Whenever someone shows me some drop-dead-cool new app or device, a secret part of me wonders if somewhere out there a UFO is stored in a big warehouse where technologists are systematically reverse-engineering its contents. I repeat myself from earlier, but across the entire span of the 1980s, the only new technology society had to absorb was push-button phones and the Sony Walkman—and even then there were naysayers saying, “Slow down!” I remember them. These days, I sometimes wake up and think, Dear God, just for today, nothing new. Please. It’s all I ask.

Certainly Weldon sees a few new things in the near future. “An umbrella with a GSM modem that glows blue when it knows you’ll be needing it. Medicine bottles that record the number of times they’ve been opened. And we need to reduce the amount people travel, and we need to reduce the ‘green shock’ of what we make.”

Maybe if I scan my conversation with Weldon closely enough, I’ll be able to figure out what the next new aisle category will be at my local Staples in a few years. I wonder if the answer might boil down to his comment about not drowning in a sea of data. What will that new invention be that turns us from dogs into cats?

Douglas Coupland is a Canadian writer, designer and visual artist. His first novel was the international bestseller Generation X. Click here to buy Kitten Clone: Inside Alcatel-Lucent from Visual Editions.

Alibaba’s CEO on Why His Company Is Killing It in China

Jack Ma, founder of Alibaba, speaks at the Clinton Global Initiative in a session,”Valuing What Matters,” Tuesday, Sept. 23, 2014 in New York. Mark Lennihan / AP

Alibaba CEO Jack Ma and the Notorious BIG may seem like two very different people—OK, fine, they’re polar opposites—but on stage at the Clinton Global Initiative’s Annual Meeting in New York City on Wednesday, Ma made it clear that he shares at least one belief with the late rapper: mo’ money, mo’ problems.

“When you have $1 million, you’re a lucky person. When you have $10 million, you have trouble,” Ma said on stage. “When you have more than $1 billion, you have responsibility.”

As Ma told his audience, that responsibility is weighing heavily on him after his company’s record shattering IPO last week, in which the e-commerce giant raised $25 billion. “People think you can spend money better than the others,” said the newly minted richest man in China. “But I only eat three meals a day. I only use one bed.”

Alibaba’s successful U.S. IPO has led someone to wonder whether the company is readying itself for a U.S. expansion, so it can take on the likes of Amazon and Google. But as Ma himself indicates, that’s easier said than done. During his appearance in New York, he hinted that such a move may require a true strategic shift for Alibaba which, until now, has benefited from a lack of quality competition in its home country.

In a charmingly humble, and delightfully loopy conversation—at one point, Ma quoted Forrest Gump, referring to him as his “American idol”—Ma

credited much of his success at Alibaba to the small- and medium-sized businesses who buy and sell their goods on his company’s many web properties, but also to the business landscape in China, where conducting commerce can be an infrastructural nightmare.

“The reason we win in e-commerce in China is because the infrastructure of commerce in China was too bad. Why e-commerce in the U.S. is not that good is because the infrastructure of commerce was so good, that e-commerce is a supplement,” he explained. “In U.S., e-commerce is a dessert. In China, it’s a main course.”

That could be one reason why Ma says part of his strategy for growing the company is to continue expanding into developing countries—countries where approximately 6.5 billion people don’t use e-commerce today. “That’s the opportunity we could have,” he says. “We’re trying to help Nigerian SMEs sell to the Philippines and the Philippines sell to Pakistan and Pakistan sell to Argentina. If we can make that happen, that’s where the money should go.”

Ma also said he plans to reinvest the $3 billion he set aside from the IPO for philanthropy in environmental and educational projects in China to “help those who want to be successful.” He said that if he, who once made $20 a month, taught himself English, and started Alibaba out of his home, could be successful in China, then anyone could be. “I never had one day of education in the United States,” Ma proudly. “I’m 100 percent made in China.”

Clues to superbug evolution: Microbiologists sequence entire genome of a Klebsiella pneumoniae strain

Imagine going to the hospital with one disease and coming home with something much worse, or not coming home at all.

With the emergence and spread of antibiotic-resistance pathogens, healthcare-associated infections have become a serious threat. On any given day about one in 25 hospital patients has at least one such infection and as many as one in nine die as a result, according to the Centers for Disease Control and Prevention.

Consider Klebsiella pneumoniae, not typically a ferocious pathogen, but now armed with resistance to virtually all antibiotics in current clinical use. It is the most common species of carbapenem-resistant Enterobacteriaceae (CRE) in the United States. As carbapenems are considered the antibiotic of last resort, CREs are a triple threat for their resistance to nearly all antibiotics, high mortality rates and ability to spread their resistance to other bacteria.

But there is hope. A team of Sandia National Laboratories microbiologists for the first time recently sequenced the entire genome of a Klebsiella pneumoniae strain, encoding New Delhi Metallo-beta-lactamase (NDM-1). They presented their findings in a paper published in PLOS One, "Resistance Determinants and Mobile Genetic Elements of an NDM-1 Encoding Klebsiella pneumoniae Strain."

The Sandia team of Corey Hudson, Zach Bent, Robert Meagher and Kelly Williams is beginning to understand the bacteria's multifaceted mechanisms for resistance. To do this, they developed several new bioinformatics tools for identifying mechanisms of genetic movement, tools that also might be effective at detecting bioengineering.

"Once we had the entire genome sequenced, it was a real eye opener to see the concentration of so many antibiotic resistant genes and so many different mechanisms for accumulating them," explained Williams, a bioinformaticist. "Just sequencing this genome unlocked a vault of information about how genes move between bacteria and how DNA moves within the chromosome."

Meagher first worked last year with Klebsiella pneumoniae ATCC BAA-2146 (Kpn2146), the first U.S. isolate found to encode NDM-1. Along with E.coli, it was used to test an automatic sequencing library preparation platform for the RapTOR Grand Challenge, a Sandia project that developed techniques to allow discovery of pathogens in clinical samples.

"I've been interested in multi-drug-resistant organisms for some time. The NDM-1 drug resistance trait is spreading rapidly worldwide, so there is a great need for diagnostic tools," said Meagher. "This particular strain of Klebsiella pneumoniae is fascinating and terrifying because it's resistant to practically everything. Some of that you can explain on the basis on NDM-1, but it's also resistant to other classes of antibiotics that NDM-1 has no bearing on."

Unlocking Klebsiella pneumoniae

Assembling an entire genome is like putting together a puzzle. Klebsiella pneumoniae turned out to have one large chromosome and four plasmids, small DNA molecules physically separate from and able to replicate independently of the bacterial cell's chromosomal DNA. Plasmids often carry antibiotic resistant genes and other defense mechanisms.

The researchers discovered their Klebsiella pneumoniae bacteria encoded 34 separate enzymes of antibiotic resistance, as well as efflux pumps that move compounds out of cells, and mutations in chromosomal genes that are expected to confer resistance. They also identified several mechanisms that allow cells to mobilize resistance genes, both within a single cell and between cells.

"Each one of those genes has a story: how it got into this bacteria, where it has been, and how it has evolved," said Williams.

Necessity leads to development of new tools

Klebsiella pneumoniae uses established mechanisms to move genes, such as "jumping genes" known as transposons, and genomic islands, mobile DNA elements that enable horizontal gene transfer between organisms. However, the organism has so many tricks and weapons that the research team had to go beyond existing bioinformatics tools and develop new ways of identifying mechanisms of genetic movement.

Williams and Hudson detected circular forms of transposons in movement, which has never been shown this way, and discovered sites within the genome undergoing homologous recombination, another gene mobilization mechanism. By applying two existing bioinformatics methods for detecting genomic islands, they found a third class of islands that neither method alone could have detected.

"To some extent, every extra piece of DNA that a bacteria acquires comes at some cost, so the bacteria doesn't usually hang onto traits it doesn't need," said Hudson. "The further we dug down into the genome, the more stories we found about movement within the organism and from other organisms and the history of insults, like antibiotics, that it has faced. This particular bacteria is just getting nastier over time."

Applying findings to future work

The findings are being applied to a Laboratory Directed Research and Development project led by Sandia microbiologist Eric Carnes, who is examining alternative approaches for treating drug-resistant organisms. "Instead of traditional antibiotics, we use a sequence-based approach to silence expression of drug-resistant genes," said Meagher.

The researchers also are applying their understanding of Klebsiella pneumoniae's mechanisms of resistance and their new bioinformatics tools to developing diagnostic tools to detect bioengineering. Looking across 10 related but distinct strains of Klebsiella pneumoniae, they pinpointed regions that were new to their strain, and so indicate genetic movement.

"By studying the pattern of movement, we can better characterize a natural genomic island," said Hudson. "This leads down the path of what does an unnatural island look like, which is an indication of bioengineering. We hope to apply the knowledge we gained from sequencing Klebsiella pneumoniae to developing diagnostic tools that could detect bioengineering."