Revisionist history at EPCOT

Several news blogs, including BoingBoing, have reported that the new refurbished "Spaceship Earth" ride at EPCOT now includes a diorama of Wozniak's and Jobs' garage where Apple got its start in the mid 1970s. Very nice. But take a look at the computer that one of the Steves (presumably Wozniak, the more technical of the two) is working on -- is it an Apple I, the computer that was actually designed in the garage? No -- it seems to be some sort of fictional primitive Lisa or Macintosh -- machines that weren't designed until years later. Why, oh why? Are they planning an diorama with Henry Ford building a primitive Taurus?

The Internet doesn't lie...

My immunologist friend Andreas Krueger has recently pointed out to me that according to a certain website the reading level of this blog is "Genius". I'm sure this is every bit as scientific as those quizzes that tell you which Star Wars character you are most like. Also, this ranking was made prior to this post -- it would be amusing if this post somehow weakened the rating...

A Life Decoded: My Genome: My Life

First of all, I'll get the required whining over the title done with -- yes, RPM, myself, and TR Gregory all have written about our annoyance with the terms "decoded/deciphered/cracked" in relationship to genomes, but there's a good chance that the title was thought up by the publisher. I would have called it "A Life in Sequence", but oddly enough, nobody asked me.

Now that that's done, how was the book? Pretty good (and I'm not just saying that because Craig's my ultimate boss and could fire me, honest -- he'd have to know who I was, for starters). It's a bit snarky in places, and some of his opponents come off as caricatures, but it's entertaining in much the same way as The Double Helix was.

The book is written as an autobiography, with bits of relevant genome information inserted in -- the gimmick is that this is the first of many "molecular (auto)biographies" that will interpret lives in the context of genomic sequences and the alleles the subject carries. Right now, it is a gimmick (although an amusing one), but I can see how in the future it might really be informative.

Much of Craig's working class youth and experience in the Vietnam War have been covered by various media stories before, but it is nice to hear it straight from Craig -- for one thing, it clears up the confusion between the shark and sea snake stories -- often these anecdotes are wrongly merged into one story.

What was new to me was learning about his pre-genomics scientific career. I had no idea that Craig's background was in biochemistry, for example. He credits that with helping him getting the early (notoriously temperamental and unreliable) automated sequencing machines to work when others, mostly from genetics and molecular biology backgrounds, couldn't.

The book is also interesting for some rather open and telling quotes -- probably my favorite is

One of my critics, John Sulston, objected that I wanted to have it both ways: "to achieve recognition and acclaim from his peers for his scientific work, but also to accommodate the needs of his business partners for secrecy and enjoy the resulting profits". I plead guilty, along with the rest of humanity, to committing the most heinous crime of both wanting my cake and eating it.

The rest of humanity indeed. Later Craig shows that many in the "holier-than-thou" public genome project also had links to the biotech industry; their primary difference from Craig seems to be that they tended to hide their conflicts of interest rather than openly declaring them.

Some of Craig's interpretations may be a little off base -- at one point Craig prides himself for not having the tenure system at his institutes on the basis that "the second rate people who thrive in a tenured environment like nothing more than to surround themselves with more mediocrity and drive out those who might excel and reveal the shortcomings of the entrenched". Well, perhaps. But the simpler explanation might be that tenure is rather hard to give when everyone is working off soft money which could disappear in the next funding cycle. And there has to be more to the story that Claire was the one who suggested merging JCVI and TIGR. In what context?

But in general, Craig's observations are dead on. Venter's opponents have tried to spread the myth that he's out to be "the Bill Gates of Biology", and whatever faults the guy has, his motivations are a lot more complicated than just the pursuit of money. Shreeve's "The Genome War" covered some of this, but it is nice to finally hear Craig's story from himself.

The Third Domain

Tim Friend's recent book The Third Domain is an odd book on two levels -- first of all, the story that one would think it tells, that of Carl Woese's discovery of the Archaea, the initial hostile reaction that the discovery met with at the hands of the scientific establishment, and its eventual acceptance by the majority -- makes up only one chapter (chapter 3) of the book. The rest of the book mostly follows field microbiologists like Karl Stetter and Eric Mathur as they collect samples (often, but not always, of archaea) from hot springs and thermal vents. Secondly, rather than being one unified whole, each chapter reads as its own story (which it may well have been; Friend is a former USA Today science writer and may be simply fleshing out articles he's already written). I'm of two minds about this book; as a evolutionary microbial genomicist (and one who has had the honor of working with Woese), I'm glad that there's a new book for the general public that acknowledges that microbes are worth studying for things other than their effect on human health; but on the other hand, I can't help but wonder if the story of the Archaea couldn't have been told in a more engaging manner. Bill Bryson, in his A Short History of Nearly Everything managed to tell Woese's story (if a bit too simplified) in an exciting chapter there. In conclusion, The Third Domain is worth a read (especially if you are interested in the subject), but the definitive book on Woese and the archaea has yet to be written.

Biologists are happier than Computer Scientists

A recent survey conducted by the National Survey on Drug Use and Health (NSDUH) compared the percentage of US workers reporting an MDE (Major Depressive Episode) in the past year across occupation, gender, and age. Some of the results were fairly predictable, such as food and service workers having a greater than average occurrence of MDEs, and I had read before that women and older people tend to be more depressed on average, but some of the other results were quite surprising, at least to me. For example, "Mathematical and Computer Scientists" had a considerably higher rate (6.2%) of MDEs than did "Life, Physical, and Social Scientists" (4.4%). Not sure where that leaves bioinformaticians....

GME 2007 Highlights

Well, I haven't blogged much lately, but there hasn't been much coverage of last week's GME 2007 (no, not this GME 2007!), other than Jonathan Eisen's brief live comments, so I figured it might be of interest to talk about some of the talks I attended there.

GME (Genomes, Medicine, and the Environment) is the meeting that was once called GSAC (Genome Sequencing and Analysis Conference), with the name change reflecting that the focus is now more on the use of genomics to understand medicine and the environment rather than on genome sequencing per se (although there was still a session on sequencing technology). It was held in San Diego, which allowed me to visit the La Jolla branch of the JCVI and to see former colleagues who have transplanted to the “left coast”.

Colleen Cavanaugh and Nancy Moran gave interesting back-to-back talks on bacterial symbionts of plants and animals and brought up many of the same issues in their evolution – namely that the genome size of symbionts seems to be correlated with the estimated age of their relationship with their host – that is that large bacterial symbiont genomes seem to shrink over time. Not that this is surprising, given that mitochondria and plastids are thought to be remnants of symbionts with larger genomes, but it is nice to see evidence of the process in progress today. The isolated environment of symbionts also seems to result in other oddities, such as increase levels of drift and chance fixation. As I am currently involved in a genome project of an endosymbiont of a cellulose-degrading shipworm, both Nancy's and Colleen's talks gave me many ideas for interesting things to look for.

JCVI's own Nobel laureate, Ham Smith, gave a pleasantly low-key talk on the status of his synthetic life project (no, bad scientific reporting to the contrary, he hasn't succeeded yet). Basically, now that his group has successfully transferred a genome from one bacterium to another, they are building an entire synthetic genome of Mycoplasma genitalium from scratch. Of course, even when they successfully transfer this they won't really have “synthetic life”, but it is clearly a step that needs to be done along the way. Again, I really liked it how Ham basically just said what he was doing without any hype – but then, when you have the Nobel, I guess you don't need hype.

A younger JCVI researcher, Yuri Gorby, presented his work on “nanowires” -- basically, structures produced by some bacteria that conduct electricity. The theory is that these allow the bacteria to disseminate electrons in a biofilm, thus freeing the bacteria from having to have direct contact with an electron acceptor. Really cool stuff, although not universally accepted yet.

Edward Bayer gave a talk about the “cellulosome”, which I hadn't heard of before, but given that I'm working on a cellulose degrading bacterium, I suppose I should have. Basically, not all cellulases are free in the cytoplasm – basically many form a complex (the aforementioned “cellulosome”) which is far more efficient than free cellulases. As Jonathan Eisen mentioned, Edward's paraphrase of Genesis at the start of the talk did seem rather off-putting, but hopefully it's just a cultural thing – perhaps in Israel such talk is just a manner of speaking and not a sign of creationism. He did mention evolution at one point, which was somewhat reassuring.

My former TIGR colleague John Heidelberg gave a talk on his work on metagenomics of cyanobacterial mats in Yellowstone Park hot-springs. Besides the interesting results, he brought up the important (if somewhat scary) observation that it is possible to assemble a genome from metagenomic data that doesn't actually exist in nature (much like nobody has the average 2.2 children).

Gene Tyson and Mary Ann Moran both talked about “metatranscriptomics”, which despite being a new “omics” (another one? geez!), is actually a really good idea – don't just sequence genomes from the environment – sequence the mRNAs to get an idea of what genes are turned on in a population in a given condition. Tyson was using microbial data from the Hawaii Ocean Time-series station ALOHA, and Moran was looking at her coastal Roseobacters.

Jonathan Eisen talked about his “Genomic Encyclopedia” which he plans to do with the JGI. Basically he plans to sequence (in a high throughput manner) hundreds of bacteria and archaea He aims to start with a pilot of 200 organisms (100 of which he'll close), but there's talk of maybe doing everything in Bergey's manual. From Jonathan's perspective, the point is to make a “happy tree of life” in which we have data to make truly representative phylogenetic analyses. As a genomicist, I find this both awesome and scary. Obviously, I'd love to have the data, but it looks like the time of “genome projects” as such is becoming as quaint as cloning and sequencing a single gene. Well, times move on, I suppose. Jonathan also talked about our Hyphomonas work as an example of how genomics helps resolve phylogenetic questions.

Shannon Williamson (now of JCVI-La Jolla) presented a talk about phage metagenomics in deep sea environments. Basically, she found that bacteria in diffuse-flow thermal vents have more lysogenic phages than do bacteria in the surrounding cold water (presumably because lytic phages would have have a hard time finding a host in a diffuse environment). Additionally, the phages are less diverse than in the surrounding waters, This talk was especially interesting to me because I helped her with some of the bioinformatics analyses, but I hadn't seen the big picture before.

Horizontal Gene Transfer from Bacteria to Eukaryotes

Can bacteria transfer genes to eukaryotes? Many people may remember the rather rash assertion of evidence that they can that was made in the initial human genome paper (and the subsequent debunking of those claims by people I used to work with at TIGR).

But just because one study was flawed doesn't mean that such horizontal transfers don't happen, and today in the advance publication section of Science a new study shows solid evidence that the endosymbiotic bacterium Wolbachia has integrated parts (in some cases quite large portions) of its genome into that of numerous strains of Drosophila, the wasp Nasonia, and the worm Brugia malayi. These aren't mere cases of "BLASTology" -- they were confirmed by PCR. Even more stunningly, RT-PCR suggests that in some cases the integrated genes are actually expressed.

Again, there is a TIGR/JCVI connection -- one of the co-first authors, Julie Dunning Hotopp, has a cube only several feet from mine -- and all today I could hear her talking on the phone with science reporters -- so congratulations to her (and best wishes that the reporters don't screw things up). Also, congratulations to all the other authors, particularly the other co-first author, Michael Clark, whom I haven't met.

The results of the study have many implications both theoretical and practical. From an evolutionary perspective, it is interesting to ponder if the ancestors of many current eukaryotic genes came from such bacterial integrations. And from a practical perspective, it really makes one wonder if discarding bacterial sequences during the assembly of eukaryotic genomic data as "obvious contamination" (as is commonly done) is really the right thing to do.