The Bloody Olive

Not really typical material for my blog, but here's a thriller even more convoluted than "Nobel Son" -- and only ten minutes long! It's a Belgian-made short film from 1996, given new life thanks to Youtube. Excellent reproduction/parody of 1940s film-noir.

The science in "Nobel Son"

Last night I saw Nobel Son, the new Alan Rickman movie where he plays an arrogant chemist who wins the Nobel prize. I don't want to talk about the actual plot, which is one of those "wheels within wheels" over-complicated thrillers that everyone has seen before at least once.

Instead, I want to discuss the Rickman character -- Professor Eli Michaelson. Granted, the plot didn't really require him to be anything else than successful and arrogant -- he could have equally been a CEO or something without changing the movie much, but let's see how well the movie captured science and its culture.

1. Michaelson's  research. Apparently it has something to do with molecular fluorescence stimulated by lasers. Given that the 2008 Nobel Prize in Chemistry (which I'm sure was picked well after this movie was completed) , did deal with fluorescence, albeit created by Green Fluorescent Protein (GFP) rather than lasers, kudos to the scriptwriters.
2. Understanding of how grad school works. This the writers did not do so well. Early on in the movie Michaelson is established as unpleasant and unethical by showing him doing a quickie in his office with one of his grad students who is unhappy with her grade. I suspect the writers only have experience with undergraduate education. Grades just aren't a major issue in grad school. If the student were complaining about her project or authorship on a paper, this would have been more plausible.
3. Choice of reading material for a chemist. During the above mentioned quickie, an issue of Cell is clearly shown on Michaelson's desk. Yes, Cell is a major journal -- but for biologists and not chemists. An issue of Science or Nature (which publish across all branches of science) or indeed a chemistry journal, would have been more plausible.
4. Amount of Prize Money. The amount "$2 million" is a major plot factor in the movie. But would a Nobel Laureate actually get that much? The prize is currently $10 million SEK (US $1.2 million at present). Plus this amount is shared with the other winners in the category (The movie never says if Michaelson is sharing the award).

10th Anniversary of my Defense -- A Retrospective

On December 2, 1998 I defended my dissertation entitled "Exploration of microbial genomic sequences via comparative analysis", the somewhat vague title referring to a collection of projects that I worked on in Gary Olsen's (pictured) laboratory at the University of Illinois at Urbana-Champaign, most notably the CRITICA genefinder (which was, until a year or so ago, still in use at JGI), and one of the earliest genomic studies of thermostability.

My thesis committee consisted of Carl Woese, Tony Crofts, and Stan Maloy (now at SDSU; I run into him at seminars occasionally). 

I don't have any pictures of the defense or the lunch afterwords after owning to a sad accident -- my parents' camera had a broken lens, and in that pre-digital era, they didn't know anything was wrong until they tried to develop the film. Still, the day sticks with me in memory. I gave what was probably the best presentation of my career (probably because I had practiced ten times or so), and the questioning was very friendly (the serious questioning had been several years before at my prelim). 

I've worked a number of jobs moving to various cities in the name of science since those days -- a postdoc in Computer Science at the University of Waterloo,  a senior bioinformatics scientist at a now-defunct biotech firm in Montreal,  living in downtown DC while working in the microbial genomics departments of TIGR and its successor JCVI,  and now in San Diego, where I'm working at the west-coast campus of JCVI. Who knows where the next ten years will take me?

Extreme 2008 and Extreme Viruses

A research expedition aboard the famed R/V Atlantis (carrying the equally well known submersible DSV Alvin) has just set sail from Manzanillo, Mexico. Its 21-day mission is to explore hydrothermal vents in the Pacific and Sea of Cortes. That's what the "Extreme" part is -- they aren't going to bungee jump or anything. 

I actually know (although not well) the two PIs who are leading the expedition -- I met Craig Cary in Australia at ISME last summer and I met Eric Wommack in Boston at ASM last spring. However, my principal interest in the expedition is that two of my JCVI co-workers, Lisa Zeigler and Doug Fadrosh, are aboard in order to collect viruses in the vent community. Viral ecology is a growing field -- viruses play a role in microbial ecology both as predators and as means of transferring genes from host to host.

The expedition has a lovely official site, and Lisa has started a blog that all of you should go visit -- blogging/journalling has a long and noble tradition in marine biology expeditions, going back at least as far as Darwin's "Voyage of the Beagle".

Is that a duck? It sure sounds like one!

Only a few days ago, my former TIGR colleague Steve Salzberg wrote about Johns Hopkins University's plans to open an "Integrative Medical Center" where herbalism and other "alternative" (that is, unscientific) treatments will be offered. That was disturbing enough given the great stature Johns Hopkins has in medical science. 

But today I received an e-mail that the East Coast branch of the JCVI, the institute where I work, as part of their "Lunch & Learn" series, is inviting a speaker from the "North Adams Wellness Corner" to talk about

"how pressure points can help relieve cold and flu symptoms. Learn easy and effective pressure points on the hands, face, and feet to relieve sinus congestion and boost your immune system".

I've only taken one immunology course and I didn't recall "pressure points" being mentioned, so I was a bit curious. Looking them up on the web, I find out that they are part of the mysticism behind martial arts! Quoting from that page, I find that 

"The Eight Brocades, an ancient Chi cultivation technique that help heal the body, prevent illness and boost your immune system while activating special pressure points. These exercises have been practised for over 1,000 years by Chinese martial arts practitioners."

Not very promising. I'd be far more convinced by peer-reviewed articles rather than the anecdotal experience of Bruce Lee and his predecessors. Why is it that nonsense sounds more profound when it is from China or India? The West also had its pre-scientific medical theories. Why not return to the Four Humours of Hippocrates? This is even older than the "eight brocades", and according to the above logic, older is better, right? I guess the reason why I'm angry about this quackery is that I have too much yellow bile ("choleric").

Badgeromics 2008, er Metagenomics 2008

I'm attending the Metagenomics 2008 conference being held locally at UCSD. There's plenty of interesting talks (see Jonathan Eisen's coverage). However, today what struck me the most (egotist that I am) was how my work was brought up in three separate talks...

Alex Worden started out the day by discussing her work on picoeukaryotes (unicellular eukaryotes less than 2 microns in size) and there were a couple of slides dealing with the comparative work that Andy and I have done as part of her forthcoming Micromonas paper.

Then practically half of Shannon Williamson's talk about her metagenomics work on marine viruses was devoted to my phylogenetic pipeline, APIS (Automated Phylogenetic Inference System), which performs taxonomic binning of metagenomic data by the automated creation and interpretation of phylogenetic trees.

Then in the evening Jonathan Eisen brought up our 2005 paper as part of the justification for his new project to sequence hundreds of bacterial and archaeal genomes.

Thanks guys. Your checks are in the mail...

The Genome Sequence of Phaeodactylum tricornutum

What's this? Another eukaryotic genome paper with me on it? I blame Jonathan Eisen for putting me on that road to ruin -- I never touched the nucleated rascals before Tetrahymena. 

But seriously, single celled eukaryotes are cool, and not Eisen but rather Andy Allen (who doesn't have a web page or blog to link to, unfortunately) is the one to blame for getting me involved with his beloved diatoms.

P. tricornutum is the second diatom genome to be sequenced, and first of the pennate (elongated) lineage. We discovered that this genome was quite different from that of Thalassiosira pseudonana, the first diatom genome to be sequenced , which is a member of the centric (hatbox/cheesebox/petri dish) lineage.  We also identified about 600 genes that we believe to be of bacterial origin in this genome. As this was part of the analysis that I did, I'm perhaps biased in that I think this one of the most interesting results in the paper. This analysis wasn't just "BLASTology" (being just based on BLAST output), but rather based on phylogenetic trees for each predicted protein coding gene in the P. tricornutum genome.

There's been some press about the paper -- including this one in the German newspaper Die Welt -- whose sub heading "Diese Lebewesen entpuppen sich als eine kuriose Mischung aus Pflanze, Tier und Bakterium" implies that P. tricornutum is a curious mix of plant, animal, and bacterium -- not exactly true, but hints at the HGT analysis that we did. There's also this press release that mentions me and Andy by name, but so far no papers have used that part :-) 

Anyway, the paper (which is under a Creative Commons License, showing that even commercial publishers like Nature can be reasonable) is up on Nature's advance publication page as of yesterday. Check it out. And the supplemental, where most of the actual data is.

The Genome Sequence of Penicillium chrysogenum

With all the work I've been doing in metagenomics, it's nice to be reminded that I still do some of the non-meta type -- yes, I was involved in the P. chrysogenum project, and the paper  (and supplemental) is now up in Nature Biotechnology's Advance Publications page prior to the print publication.

We've actually gotten a little bit of press -- the BBC has a brief article here. 

P. chrysogenum is one of those obvious genomes people are surprised to learn haven't been sequenced yet (well until now). While a "pure" biologist may yawn and say "it's just another filamentous fungus -- haven't we sequenced those already?", there is real practical potential for metabolic engineering of new antibiotics from this genome given that researchers have been doing work on the bug for over 60 years. Besides, the genome wasn't completely uninteresting even from the viewpoint of basic science -- we snuck in a fairly controversial fungal phylogeny in figure 2 -- and I stand by it as we used far more data in our alignments than in previous studies.

[updated links to final published version 10/14/08]

RIP David Foster Wallace (1962-2008)

You may have heard the news; last Friday the literary Wunderkind of the 1990s, David Foster Wallace, hanged himself in his Southern Californian home.  I have to admit that I haven't thought much about Wallace since the turn of the century, but his 1996 Infinite Jest was (and perhaps still is) one of my favorite novels.  

In many ways, _Infinite Jest_ was the quintessential 1990s American novel -- the conceit of the story was that American economic and cultural influence would simply keep growing and growing in the future -- as indeed in those heady post-Cold War times it looked like it would.  Of course, part of Wallace's point was that would not necessarily be a good thing given the crass commercialization of US culture  -- his idea that names of calendar years would be sold to the highest bidder is entirely believable given that we live in the world of PETCO Park and Qualcomm Stadium.

Many people have compared Wallace to Bret Easton Ellis (Less than Zero, American Psycho), and in a way they have a point. Certainly, Wallace was far more erudite and literary, but just as Ellis captured the "soul" of Reagan-era America, Wallace did the same for the Clinton era. Who will do the same for our current era?

Jacques Ravel in the New York Times

I'm back from Australia (although jet-lagged), and looking through the NYT science articles that I'd missed over the past week and a half, I discovered this article about the techniques used to establish that the mailed anthrax powder that killed photo editor Robert Stevens in 2001 was from the RMR-1029 strain (indirectly suggesting Bruce Ivins as the culprit, although the article stresses that is still as yet unproven, despite Ivins' suicide). 

It's a very interesting article, but I have to admit that what drew me in initially was the photo of my former TIGR colleague Jacques Ravel - while articles featuring Craig Venter are too common to mention these days, it's nice to see some coverage of other people I've worked with.

ISME 12 -- More Highlights

On Wednesday we had a free day -- a very clever thing that I wish other conferences would imitate -- having a free day in the middle allows a bit of a mental breather to prevent burn out from all the scientific sessions. We used the time to go to Kuranda and environs. Kuranda is located in a rainforest and is reached through an aerial cable tram similar to that found in Palm Springs, California (but even more impressive given the length of the trip and the beauty of the scenery). The village itself is a bit of a tourist trap, as expected.

There's a nice, although small, museum called the "Rainforest Interpretation Centre" that helps visitors learn about the forest through exhibits and interactive displays. One of the oddest things was the three languages used -- English (of course), Japanese (understandably -- much like Hawaii, North Queensland seems to be a Mecca for Japanese tourists), and finally, German of all things! Of course I couldn't resist playing with interactive displays where "Welcher Baum ist das?" was asked. I understand that Europeans visit Australia, but why German in particular and not say, French and Spanish as well?

Thursday was back to science. Craig Cary talked about metagenomics in the Antarctic Dry Valleys -- I hadn't realized that there are ice-free deserts in Antarctica, but apparently there are, and there's cyanobacteria (in particular) living in them. About midway through the talk, Craig shifted gears and started talking about (I'm not making this up) mummified seals! Apparently, Antarctic explorers have long known about these naturally mummified seal corpses (some over a thousand years old) , but Craig was interested in investigating whether the microflora underneath the seals was different than in the surrounding soil. Not surprisingly it was -- the Antarctic deserts are very carbon and nitrogen starved and a slowly rotting thousand year old seal is a much better source of nutrients than anything else around. Craig even transplanted a seal from one place to another to see if he could influence the new environment in the same way, and the experiment worked.

Rick Cavicchioli talked about the genome of Methanococcoides burtonii. I liked that. These days traditional genome projects are somewhat unfashionable (and unfundable), but not everything has to be metagenomics (although Rick is doing that too). Amino acid comparisons with relatives living at higher temperatures were a major part of the story of this genome -- and that work was pioneered by my fellow blogger (and commenter) Neil Saunders, as Rick acknowledged.

I will try to write up a final writeup on the last talks soon. And yes, that is a real live koala with me in the picture.

ISME 12 -- Highlights of Tuesday

On Tuesday, Phil Hugenholtz talked about his work in metagenomics of a hypersaline mat in Guerro Negro, Mexico. What makes this project a little different from typical "bulk" metagenomics projects such as the Global Ocean Survey is that the peat-like mat has distinct layers of microorganisms even within a centimeter thick sample and these layers can be separated and analyzed individually. Phil and colleagues analyzed 10 layers of the mat and found distinct differences. Particularly interesting was the overabundance of chemotaxis genes on the oxygenic/anoxygenic boundary, which he explained by the fact that microbes that live near the border have to be able to move into their preferred layer as this boundary shifts over the duration of a day. Phil also looked at amino acid bias between layers, which brought back fond memories of my work in grad school linking amino acid differences to thermostability.

Gene Tyson talked about metatranscriptomics, or metagenomics on transcripts (well, cDNAs anyway). As I have a grant funded (with Andy Allen) to do metatranscriptomics on eukaryotic phytoplankton, I found it interesting (although depressing) that despite all the optimizations to avoid it, still 50% of their cDNAs are rRNA.

I had lunch with Rick Cavicchioli and members of his group as JCVI's field biologist Jeff Hoffman hopes to get me involved in the analysis of the Antarctic lake metagenomics data he is generating in collabioration with Rick's lab.

In the afternoon, I presented my poster on "Large Scale Analysis of Nitrogen Utilization Genes in the Indian Ocean" -- basically a bioinformatic analysis of the GOS II data in the context of several genes involved in organic vs inorganic nitrogen uptake and usage. While I wasn't swamped with visitors, a dozen or so people stopped by and gave useful suggestions.

In the evening we had more keynotes from Roberto Kolter and Norm Pace. Kolter's talk (on the genetics of biofilm production in Bacillus) was really wonderful -- and not just for the knowledge imparted -- Roberto is a truly gifted public speaker, a rarity among scientists.

Norm's talk was the same "don't use the term 'prokaryote'" talk that I've heard twice already. Now don't get me wrong -- I have enormous respect for Norm and even quite a bit of agreement for the meaningless nature of the term "prokaryote", but really, I think nearly everybody in the field has either read his paper on the topic or heard him speak on it at least once. This might be forgiven if Norm was some retired scientist who was no longer is generating any new ideas, but happily Norm and his lab are still quite active -- I think everybody would find talks on new work from his lab much more interesting than yet another version of the same "prokaryote" talk.

ISME 12 Cairns - Highlights of Sunday and Monday

The first two days of ISME went quite well. First of all, I have to give the organizers high marks for actually providing a conference bag worth having (BTW, it would be interesting to figure out someday where and when the custom of "conference bags" started -- why does every conference assume that attendees need a conference-specific bag?) Rather than the nearly useless tote bags which one often gets, the ISME 12 bag is a nice high quality backpack that will be worth keeping after the conference. Conference bags may be a minor issue, but a quality bag is a nice touch.

Bo Barker Joergenson gave a nice keynote on Sunday night on the subject of the "deep biosphere" by which he means microbes living deep in the sediment at the bottom of the ocean. Ships have returned drilled cores even from a couple of kilometers down that contain microbial cells. For many years there was debate over whether these cells were actually alive or just the "corpses" of cells that drifted down and never decayed, but now there is general agreement that there are living cells. What there isn't agreement at this point is what type of cells there are. Some groups, using Q-PCR have concluded that the primary players are bacteria; others using FISH-IPL say archaea are. As a bioinformatician, I find this conflict of experimental methods disturbing. Still, the "deep biosphere" is a fascinating topic to me.

After the keynote we had appropriately Australian entertainment; a group of local indigenous Murri demonstrated some traditional songs and dances and the use of firesticks.

On Monday the main series of talks began. Curtis Suttle talked about inferring the host species of marine viruses through phylogeny. He began with some fascinating statistics; there are 10^30 viruses in the ocean, and if they were laid end to end, they would stretch for 10^7 light years! And they contain more carbon than 75 million blue whales. So what exactly are these viruses infecting? Suttle has developed an interesting method where he first calculates phylogenies of viruses with known hosts, calculates the average genetic distance between viruses that infect the same host, and uses this distance to cluster sequences of viruses that infect unknown hosts. He then looks for correlation between occurrences of members of these clusters with morphologically different hosts in micrographs to assign presumed hosts. Obviously, morphology is a crude measure of species in any set of organisms (and particularly so for microbes), but it is a useful start.

Forest Rohwer, probably the best known researcher of marine viruses, gave a talk about many different projects his lab is pursuing. What I found most interesting was his idea of measuring the energy usage of phages by measuring temperature in calorimeters containing bacterial cultures with and without phages.

C.D. Long presented a good example of what I find most interesting in science -- the application of a technique developed for one problem to a different one. In this case, she utilized the traditional "checkboard" method (developed by ecologists studying island biogeography) to analyze the co-occurrence of different microbial species living on human teeth. I'll have to read up on the method to see if maybe I could do something similar.

And Mitch Sogin presented on his idea of the "rare biosphere" -- the idea that most microbial species are very low abundance organisms. I've heard Mitch talk about this idea before, but this talk was more technical and included more details --- not only of his experimental methods but also of his VAMPS analysis system. I've spent a lot of time basically writing my own version of many of the methods there because I didn't know the system existed.

P.S. Qantas found Lisa's bags.

ISME 12 in Cairns, Australia

I realize that I've been a non-blogger as of late, but on the off chance some of you still have me in your feeds, I'll try to write something about the ISME (International Society for Microbial Ecology) meeting that starts this evening in Cairns (Northeast Australia, near the Great Barrier Reef).

Getting here was a bit of an adventure; coming into Sydney we were instructed that we must go through customs and retrieve our luggage before continuing on to any domestic flights. So I dutifully did that and waited for my luggage to show up at the carousel. It didn't. It turns out that because my Sydney-Cairns flight actually was the first jump in a Sydney-Tokyo flight, it didn't count as a "domestic flight" and I was actually supposed to go through customs in Cairns and collect my baggage there. After all this was figured out I very nearly missed my flight to Cairns -- as I raced through the Sydney airport to the departure gate I was one of those annoying passengers that you hear getting paged for the last call for their flight. But I made it -- and so did my luggage-- which is more than could be said for my friend Lisa's -- she still doesn't know the status of her baggage and whether it is lost for good.

But here we are in Cairns. As Lisa notes, the city is much like the San Diego that we left from in look and weather. Well, maybe how San Diego would look if Canadians had built it or something -- it does have the distinct Commonwealth feel somehow that I recognize from my time living in Canada.

More posts (with pictures and actual science) will follow.

RIP Karlin (1924-2007) & Carlin (1937-2008)

Within a span of about six months we have lost two greats with homophonic surnames -- Sam Karlin, the national academy belonging statistician whose pioneering work in computational biology lead to the statistics behind BLAST (as well as more obscure programs), and now the great comedian George Carlin. Many people may think that besides their name, these two people had nothing in common. Not true.

For example, Carlin as well as Karlin has contributed to statistics. Who can forget his great insight "Just think of how stupid the average person is, and then realize half of them are even stupider!"? And before you object that he should have used "median" in that sentence, be aware that the statistical use of "average" need not mean "mean" (in the arithmetic sense) -- the median can legitimately be called an average as well.

And Karlin was a master of the pithy one-liner himself: "The purpose of models is not to fit the data but to sharpen the questions". Well, maybe it didn't bring down the house when he said it, but it's something worth always keeping in mind.

Ralph Lewin's algal physiology papers in Esperanto

Ralph Lewin's interests intersect mine in two quite different ways. First of all, Lewin is a renowned marine microbiologist, and most of my current projects are marine as well. But secondly he is well known among fans (of which I am one) of the artificial language Esperanto, even being the co-author of a translation of "Winnie The Pooh" into the language. What I hadn't known until today was that Lewin had combined his interests in two papers from the early sixties: Difektita Aŭtotrofo de Mutaciita Chlamydomonas (Defective Autotrophy of Mutated Chlamydomonas) and La Enpreno de Strontio en Kokolitoforoj (The Takeup of Strontium in Cocolithophores). In both cases Lewin wrote papers which except for an English abstract, were entirely in Esperanto. And while it's true that Esperantists have organizations such as Akademio Internacia de la Sciencoj San-Marino that occasionally publish scientific reports in Esperanto, Lewin's papers were in a mainstream journal -- Plant & Cell Physiology. Makes me wonder what the neesperantistoj thought when they saw the papers...

ASM 2008 -- Interesting Talks, Part 1

Well, I'm back in San Diego, and people have been asking me about ASM (in person, if not in the comments), so I suppose I ought to fulfill my promise and actually write something about the talks.

National Academy member Lucy Shapiro gave a very interesting retrospective keynote on the history of her work on Caulobacter. Having worked on Hyphomonas, a related organism, I found it obviously relevant, but what I found especially interesting was the modest style of the talk. Lucy openly admitted that most of the work was done by her many students and postdocs over the years, and rather than just include their names on an unreadable slide at the end, she mentioned them by name in her talk in the relevant place as she discussed experiments that led to various discoveries about the development and cell cycle of Caulobacter.

Howard Frumkin of the CDC talked about doing "green science", reminding us that biomedical research uses over twice the amount of energy per unit space that the commercial sector does, and that it is important for scientists to "green their sector first" to avoid looking like hypocrites. Although he gave many interesting suggestions to reduce the environmental impact of science, I don't recall him questioning the need for big conferences like the ASM where thousands of scientists fly in from thousands of miles away. Replacing those with video conferences (admittedly much less fun) would greatly reduce the carbon footprint of science.

My ultimate boss, J. Craig Venter, gave a talk about current work in the Global Ocean Survey. Memorably, he started his talk with "I'm J. Craig Venter from an institute of similar name..."

Jonathan Eisen spoke on phylogenomics (link is to Kimmen Sjölander's page on the subject) and origin of novelty, nicely illustrating this rather theoretical notion that he originated with practical examples in his own research. Speaking of Eisen, the picture above was taken at a Red Sox game that I attended with Eisen, Eric Wommack, Jacques Ravel, and some of Eisen's Boston-based relatives. The bearded guy in my picture is Eisen himself, and if you zoom in, you may notice that he has "RecA" written on his hand. Don't we all write the name of our favorite proteins on our hands?

In Boston for ASM 2008

Well, it's time for the ASM (American Society for Microbiology) general meeting, and this year the venue is Boston. So 11,000 microbiologists have descended on Beantown this week - if you're a local and were wondering why those strange people on the "T" today were talking about Bacillus anthracis, don't worry - they (probably) weren't bioterrorists.

I'll give more detailed information on the talks in later posts, but I'd just like to add to Jonathan Eisen's critique of the structure of the meeting. First of all, it is extremely annoying that they are aren't dedicated poster sessions where the rest of the conference stops -- today, for instance, I had to chose between poster sessions and attending hour long talks by such luminaries as Ed DeLong and Mary Ann Moran, which nearly completely overlapped the poster sessions in time. What's worse, several students of Moran were presenting their posters while Mary was giving her talk, presumably depriving those students of their most interested "customers".

Another exciting event in Boston is that my good friend John Tsang (no, no, not this John Tsang), who was a masters student in the group where I did my postdoc, and with whom I later worked in industry, has just earned his doctorate in biophysics from Harvard. I have to admit feeling a bit of pride in this because I encouraged John to go back to grad school and wrote one of his letters of recommendation. John is going to go through the formal convocation on Thursday, and pictured is John all dressed up (next to his wife Amelia).