Monday, June 30, 2008

Looming news

Just having some fun with/at Carl Zimmer who claims he has some news to post very soon. See

Top five metaphors Darwin considered and rejected for "The Tree of Life"

Well, as I am desperately trying to prevent Hollywood from corrupting the term "Tree of Life" and I got to thinking. Why did Darwin and others have to use the metaphor of a tree to represent the branching history of organisms through evolutionary time? Why did other metaphors not get used? Well, thanks to a little research I did by communicating with Darwin directly (as I did when he announced his endorsement of Obama), I have found out that Darwin went through many other metaphors before settling on the "Tree of Life." (note the tree-like figure here which is based on the one figure in the Origin of Species).

And here are the top 5 other such metaphors for what is now known as "The Tree of Life"

  1. The coral of life. Darwin particularly liked this one as he did some work on marine organisms. But ultimately he rejected it because he was worried about anti-evolutionists killing coral to get back at Darwin.
  2. The watershed of life. Rivers exhibit branching patterns much like trees. The big problem Darwin saw was that sometimes separate river branches reconnect to each other, which did not follow his model for descent. If only Darwin knew about lateral gene transfer.
  3. The blood vessels of life. Darwin was desperate to find visceral connections for people to evolution. This one would have been great. The big problem here was the "going" and "coming" nature of arteries and veins.
  4. The shrub of life. Thus turns out to have been one of Darwin's favorites because it captures the richness of diversity more than a sparsely branching tree. However, shrub, even then, was used as a derogatory term to refer to height challenged individuals. And Darwin did not want to upset this key constituency so he avoided this term.
  5. The lungs of life. While this has some positive features (e.g., it is unidirectional like a tree), thankfully Darwin did not stick to this or we would have competition from "LOL" for all the domain names.

    Other possibilities included "the Plumbing System of Life" and "the Highway Map of Life". If you know of others Darwin may have considered, let me know.

Friday, June 27, 2008

Calling all evolutionary biologists - protect the "Tree of Life" from extinction by Hollywood

OK, I am getting worried. As I wrote a few weeks ago, there is a new movie coming out supposedly next year called "The Tree of Life" starring Brad Pitt, Sean Penn and others. Well, the movie sounds like it could be good. But though this may sound like a cool thing to those of you out there who study the Tree of Life in some way, we are at risk here. There will soon be 100s of blogs, web pages, news stories, etc. writing about the Tree of Life movie. And uses of the Tree of Life by evolutionary biologists will lose their google rankings. The term "The Tree of Life" is at risk of a form of extinction.

So what are we to do? I am calling on all evolutionary biologists and bloggers and biologists in general to to link to other sites that use the term as much as possible. For example, you can add a link to my blog, which is after all called "The Tree of Life."

So please, add links to some Tree of Life pages. And start using the term yourself as much as possible.

Here are some places you should link to
Please post additional links in the comments here and please help save "The tree of life"
Note - here are some sites responding and helping save "The tree of life"

Thursday, June 26, 2008

Jelly Bellies in the New York Times

Well, Jelly Bellies, a semi-local institution (they are based in Fairfield for those who have not seem them from I-80) has gotten some good press in the Times today. I hear they have a nice tour that kids and adults like but we have not done it yet.  I must say, I like their Sport Beans when I go for bike rides.  Anyway, just good to see local businesses getting some props in the Times.

Combinging two of my favorite things - chocolate and genomes

Well, the Mars company has really done it now (see Unwrapping the Chocolate Genome -from They are planning to sequence the cacoa genome. Genomes and chocolate. Man are they going to get every bioinformatics person I know to apply to help out with this project ...

Some little notes on the project:
  • They plan to release the data for public use: "Mars plans to make the research results free and accessible through the Public Intellectual Property Resource for Agriculture, a group that supports agricultural innovation, as they become available. The intent is to prevent opportunists from patenting the plant's key genes."
  • They are doing this in a collaboration with IBM
  • Good quote by Howard Shapiro: "We have the ability as a private company to take charge of the future," Howard-Yana Shapiro, global director of plant science for Mars, said."
So -even though I pondered whether this was science by press release, a friend of mine convinced me it was not and this was just getting out the word on the project. For other details see

Wednesday, June 25, 2008

Swimming the Mirror: Poems for My Daughter on KDVS Today at 5 PM

Brad Buchanan will be discussing and reading from his new book of poems, "Swimming the Mirror: Poems for My Daughter" (Roan Press) on KDVS 90.3 FM today (Wednesday) at 5pm. Please consider tuning in. Also available onlne at

Why I am writing about this?  Well Brad and I used to play street hockey together in grad. school at Stanford.  No - neither of us started Google as did other street hockey players from Stanford.  But you should check out Brad's new book of poems from Roan Press and also can see some of his past stuff at an old blog here.

Roan Press is a new Sacramento area publisher. In the email I got they say 
"Please mark your calendars for Roan Press's first Book Launch Party at the Book Collector (1008 24th Street) on July 23 at 7:30 pm. Roan Press is a new Sacramento publisher with an interest in poetry, fiction, books of essays and other genres. We particularly welcome submissions from Northern California writers, but are open to work from anyone, anywhere. Please also watch for our website,, which is coming soon"

Tuesday, June 24, 2008

Overselling genomics award #4: University of Western Ontario and Graham Thompson on honeybee altruism

In my blog I give out some snarky awards for things that annoy me including the Genomics by Press Release Award and the Adaptationomics Award and the Overselling Genomics Award. Sometimes I really want to give something an award but I am not sure what it should get. That is the case here. There is what I find to be a painful press release on "Selfish Genes" in honeybees put out by University of Western Ontario. This press release relates to a paper being published in Genetics. on QTL mapping in honeybees and searching for alleles/genes that suppress the reproductive activity in worker bees. This suppression is a form of altruistic behavior in a way and has been the subject of a good deal of research. Basically, the ended up mapping some of the suppression to a few regions of the genome.

The press release however, goes way way overboard in interpreting their results and claiming "New Discovery Proves 'Selfish Gene' Exists." They imply throughout the press release that prior work simply suggested that selfish genes were theoretically possible in this case and that now with their results they have been proven. For example they quote the lead author Graham Thompson:
This means that the 'selfish' gene does exist, not just in theory but in reality.
This is way beyond an overstatement. Their results are nice and interesting but they are part of a continuum of work on bees (and other selfish systems) and do not in any obvious way suddenly prove the existence of this selfish gene compared to prior work that they imply was just guesswork. I am personally baffled by the extent of this claim -- basically ignoring work by many others as well as work in a variety of systems outside of bees. They end the press release with the following:
"This basically provides a validation for a huge body of socio-biology," says Thompson, who adds the completion of Honey Bee Genome Project in 2006 was crucial to this discovery.
For that last statement, I am thus giving them my "Overselling genomics award" #4. But they easily could have gotten a few others.  

NOTE - I had changed the award to just U. Western Ontario and not including Thompson because it is the University that appears to be responsible for the press release not Thompson.  However, a commenter (Oliver) convinced me that if we want to clean up press releases we need to make the scientists involved in the story help make sure the press releases are clean, so I put Thompson back in.

Hat tip to T. Ryan Gregory for pointing this out. And you should check out his new Genomics by press release "award" at his blog Genomicron. I will probably be writing about the same story soon.

Monday, June 23, 2008

Extremophiles getting some props too

With the Mars Lander scratching the surface of the Red Planet looking for indications that life could exist there, the time is ripe for some public education about microbes and extremophiles. And fortunately the press is picking up on this possibility. For example, CNN.COM has picked up an AP story on extremophiles: Life in Earth's toughest places; how about Mars? -

In the article, Alicia Chang from AP writes:
But if there were past or present life on the red planet -- a big if -- scientists speculate it would likely be similar to some extreme life on Earth -- microscopic and hardy, capable of withstanding colder-than-Antarctica temperatures and low pressures.
Most living things on Earth thrive not only in the presence of water, but also need sunlight, oxygen and organic carbon. But the range of conditions in which life can survive has been expanded with recent discoveries of micro-organisms trapped in glaciers and rocks or living in volcanic vents and battery acid-like lakes.
The AP article is quite reasonable, as far as science reporting goes. However, there is some stink going on in the bloggosphere about AP bullying bloggers regarding fair use so you might want to check out AP: Stupid, it hurts! and AP Files 7 DMCA Takedowns Against Drudge Retort and AP/Drudge Retort “Resolution” Leaves Fair Use Questions Unanswered.

UC Davis Bodega Marine Lab getting some props

Now, I have written here before about the spectacular site for UC Davis' Bodega Marina Lab in Bodega Bay). And lest anyone not believe me, Bodega Bay and the Marine Lab has been written up in the San Francisco Chronicle in an article entitled: Marine lab a spectacular spot on Bodega Bay.

The article lead in is all you really need to know:

Mention Bodega Bay, and the first thing that comes to mind - even now, 45 years later - is Tippi Hedren getting her head pecked by a gaggle of sociopathic seagulls. The town's visitor center hands out 8,000 maps a year pinpointing where Alfred Hitchcock filmed the most memorable scenes of the 1963 classic "The Birds."

But each year, 10,000 to 12,000 people travel to a spectacular spot west of town to visit a less-famous site, the Bodega Marine Laboratory, a UC Davis outpost where about 100 graduate students and scientists study underwater life along the Northern California coast.

Each Friday afternoon, from 2 to 4, docents lead free, hourlong tours that wind through parts of the sprawling complex. It soon becomes clear that visiting a marine lab isn't anything like visiting for-profit aquariums, with their polished tanks and fancy signs. Here, the only live exhibits are a tide pool and three small aquariums.

Mind you, Bodega Bay itself is not the most happening town in the world. But it has a few stores, restaurants and cafes (which they review some of in the Chronicle article). The lab is also the site for the "Workshop in Applied Phylogenetics." One cool thing about this workshop is that the organizers have begun building a Wiki to gather information on phylogenetic methods and tools and this wiki is open to everyone to use and contribute to. So if you are interested in phylogenetics you might want to check out the wiki and start adding to it. And you might want to keep an eye out for announcements for next years course.

Open Science Highlight -- JoVE: Journal of Visual Experiments

I am starting to browse around at JoVE (the Journal of Visualized Experiments).  This is an open journal dedicated to publishing biological research in a visual format.  It is pretty cool.  Some good videos include ones by Jared Ledbetter's group on studying microbes inside termites (see Layers of Symbiosis - Visualizing the Termite Hindgut Microbial Community
and Extracting DNA from the Gut Microbes of the Termite (Zootermopsis nevadensis)) for example.  Others of interest to this blog include one by Ed Delong's group on Large-Scale Screens of Metagenomic Libraries. 

Anyway - JoVE is definitely worth checking out ... visual presentations are probably the way of the future ...

In addition to experiments, JoVE also has some interviews.  For example, I am embedding a nice video from JoVE with a talk by Ed Delong on microbial communities (Microbial communities in nature and laboratory - interview (Video Protocol).   To view the embedded video click the play button below.

Saturday, June 21, 2008

How Darwin won the evolution race

There is a cool article in the Observer today on the "race" between Darwin and Wallace on publishing the theory of natural selection (How Darwin won the evolution race | Science | The Observer).

When I read this I cannot help wonder what would have happened if this race had happened today. With publishing and the spread of ideas occurring at a much slower pace in the past, Darwin could afford a bit of time to polish up all the lines of thought and evidence presented in the Origin of Species. It is really his work on building up such evidence that helped convince people of the importance of natural selection. So - if this had happened today - Darwin and Wallace would certainly have been on Science Friday. Lots of bloggers would have written about it. But would Darwin have taken the time to polish up his loose ends or would he have just rushed out his short paper on natural selection and then gotten caught up in the hype and debate?

Anyway, the article has some good bits both about the history and about the acceptance (or lack thereof) of evolution and natural selection today. My favorite lines is:
Natural selection is simply too important for society to live without it, he (Steven Jones) argues. It is the grammar of the living world and provides biologists with the means to make sense of our planet's myriad plants and animals

Friday, June 20, 2008

Tree of Life Runners Web Notes 6-20-2008

Just some little notes here in lieu of more detailed posts.

Street View for Davis on Google Maps

If you have not already heard, Google Maps has added the "Street View" function for Davis, CA where they drove around in a truck and took pictures of the front of every address.

See here  for a view of Central Park.
or click on the pic below.

View Larger Map

Oh - and here I am .... loading my car up for a trip.

View Larger Map

Wednesday, June 18, 2008

Prochlorococcus on Science Friday

Well, I wish I had known this in advance and I would have posted something about it here before last Friday. But anyway - Penny Chisholm (from MIT) and her beloved Prochlorococcus (important photosynthetic marine microbes) were featured on Science Friday last week. Fortunately, NPR broadcast's like ScienceFriday are a form of Open Access. And you can listen to Penny here. It makes for some good listening -- she has some good lines about the importance of microbes as well as the need for more support for work on microbes. She also gives a good plug for the Gordon and Betty Moore Foundation's Marine Microbiology Initiative (full disclosure - I just got a grant from this program). Note - the Science Friday host makes a bit of a blunder when at the end he asks if they have talked about viruses when a few minutes before she had done exactly that (for more on Prochlorococcus viruses see the Sullivan et al PLoS Biology paper here). You can also get a video of Penny giving a talk here.

Are You Intellectually Clean?

Well, brain doping continues to be an issue, long after the buzz of April Fools Day is over. Now comes what I think must be a spoof of some kind: a site where people can make an "Academic Oath" saying they are clean by putting the following on their CV or WebSite:
For the honour of humanity and the integrity of the academy, I declare I have not, nor ever will, use any drug for an intellectual advantage. See,
This reminds me a bit of the PRISM spoof "PISD" but I am not sure if Academic Oath is really fake.

Freeing My Father's Scientific Publications Update

Well, I have made some progress already in my quest I began on Father's Day to free up the scientific publications of my father (see The Tree of Life: Freeing My Father's Scientific Publications).

I wrote to the powers that be at the journal "Endocrinology" asking about when back issues might be made available. And I got a VERY quick reply from someone from Highwire Press which is the place that puts out Endocrinology on the web
Dear Jonathan Eisen,

The Endocrine Society is currently in the process of loading back issues for all of their journals. It will most likely be six months before back content is online.
The person who wrote back was almost apologetic about how long this might take but I am personally very pleased. Given that Endocrinology says the make all articles more than a year old available for free, this likely means that my father's three papers in Endocrinology will soon be available for free online. This then changes my tally to:

Pubmed Central: 3
Free access: 17
Fee access: 11
Unavailable: 4

Getting better. Of course, I want them all to be as widely available as possible so I am still going to work to move everything up the list towards Pubmed Central. Also, my brother suggests (in the comments to my previous post) that since my father was a government employee we should be able to just post his papers online. I think this is a good option but I still will be working on the "official" channels to see what happens.

Since I made the original posting there have been some useful comments about what I might do on some other sites. See for example, this FriendFeed discussion (I have just discovered FriendFeed and it seems quite cool but I am not sure if everyone can see this discussion or not so please let me know if this link does not work).

I will keep posting on my progress as well as what I learn about Copyright, Free Access, etc.

Tuesday, June 17, 2008

ASM Bloggers Breakfast and Lost Notes

Oops.  I wrote some additional notes to post for the ASM Meeting but seem to have deleted or misplaced the file.  One of the things I wanted to write about was how glad I was to have dropped by Moselio (aka Elio) Schaecter's breakfast discussion of blogging and microbiology.  Fortunately Moselio has posted about this on his wonderful "Small Things Considered" Blog.  I note it was also good to finally meet Tara Smith, who also has a great blog "Aetiology" and to meet/remeet some of the others.  I was also inspired by some of the people there to start rebuilding my "OpenWetWare" lab page.   Though I arrived late, the breakfast for me was the most inspiring thing about the whole meeting ...

Tree of Life hitting the big screen ...

The "Tree of Life" is really hitting the big time. I just found, in a google search, that there is a movie coming out in 2009 called, "Tree of Life (2009)." The plot summary is as follows:
In a mystical world of folklore, several individuals embrace in a race to find the Tree of Life, said to give immortality, fertility, and other supernatural powers
And if that does not excite you, well, maybe this will. The cast includes Brad Pitt, Sean Penn and a few other big shots. Stay tuned here for more updates, or check out the wikipedia page for the movie here. Also see: Brad Pitt and The Tree of LifeBrad Pitt Scales Tree of Life,  Malick's Tree of Life caught on cameraBrad Pitt looks young in Tree of Life movie

Monday, June 16, 2008

Obama on Teaching Evolution

I finally found what appears to be a credible reference to Obama's views on teaching evolution. In an April Blog from the Dallas Morning News they quote the York Daily Record:

He was asked about the teaching of intelligent design and evolution in public schools. His response: 

I'm a Christian, and I believe in parents being able to provide children with religious instruction without interference from the state. But I also believe our schools are there to teach worldly knowledge and science. I believe in evolution, and I believe there's a difference between science and faith. That doesn't make faith any less important than science. It just means they're two different things. And I think it's a mistake to try to cloud the teaching of science with theories that frankly don't hold up to scientific inquiry.

McCain seems to have gone silent on this issue although I have pointed out that in the past that he was clear about science being taught in science classes. Seems like he is trying to steer clear of this issue. What ever happened to the straight talking McCain?

Freeing My Father's Scientific Publications

Today is Father's Day. It was a great day for me, hanging out with my kids and wife and doing things around town here in Davis (we kind of made it Father's Weekend and did some activities on Saturday too). Despite the wonderful weekend, this day is also filled with melancholy for me when I think about my father, Howard Eisen, who died when I was a freshman in college. I miss him greatly. But whenever I think about him I think about how he almost certainly would be really proud that his two sons (me and my brother Michael at Berkeley) are now scientists.

You see, my father was a scientist too --- an MD who did research at the NIH, focusing mostly on hormone receptors. Given my propensities for putting things on the web and trying to disseminate scientific information, I cam up with a plan last night to create some sort of web page in his honor with some information about his work and his life.

The thing is, I actually know little about his work, because while I was growing up, my parents never really talked about the details of their work (my mom is a scientist too). Sure, we went to the NIH occasionally and most of my parents friends were scientists. And they talked sciency talk. But they did not really discuss details of their work. I think in the end, this is partly why my brother and I did not shun the family business and went into science.

So, of course, being the obsessed Open Access advocate, the first thing I decided to look at was what publications of my fathers I could get my hands on. This was both to read them and to make them available on this tribute page.

So - my first step in this journey was to search Pubmed for Eisen HJ. And then I had to remove the publications by another Eisen HJ. And so I was left with 35 publications in PubMed (I know he had some other articles as well as chapters in books and such but this is a good start). So then I asked - which of these were available online in one way or another. According to Pubmed 24/35 were available online. Of those available online:
  • Pubmed Central: 3
  • Free access: 13
  • Fee access: 8
  • Unavailable: 11.
This made me both happy and sad. I was glad to see some of his publications in Pubmed Central (thanks to PNAS and the Biochemistry Journal for putting them there). It was also good to see many available for free, even if this was only at some journals site. So - thanks to journals like J. Biol. Chem. for making the material available online for free. But I was a bit saddened to see how many of his papers, which are now all over 20 years old, being available only for a fee. And I was also a bit saddened to see how many had not yet made it into the digital world.

So - what to do next? Well, my goal is to get access to all his papers and then to free them up to the world. So my first step was to see if any of the ones that Pubmed did not have links for might be available online anyway. And indeed a few were. For example, Pediatric Research back issues are available online. And these are free. In addition, his papers in Biochemistry, J. Steroid Biochemistry and Advances in Genetics is available for a fee but it is not linked from Pubmed. So with this information the new tally was
  • Pubmed Central: 3
  • Free access: 14
  • Fee access: 11
  • Unavailable: 7
Getting digitized.
So for those 7 that are currently unavailable (at least anywhere I could find) digitally, my next step is to try and lobby the journals to make them available. For some journals, this has some hope (well, not per se my lobbying, but they may make them available). For example, Endocrinology has some back issues available but just not all the way back to some of my father's publications in that journal. So, I wrote to the journal Endocrinology using the link from the journal site and asked what their plans were for older issues. And I will post here if I get a response. (( UPDATE - THESE ARE TO BE MADE AVAILABLE SOON ACCORDING TO HIGHWIRE PRESS.)) I am doing the same for all the other unavailable publications, although some of the journals seem to not exist anymore.

Convincing "free" access journals to deposit old papers in PMC.
My next goal is to see if the "free" access journals have any plans to submit stuff to Pubmed Central. Yes, I know PMC is not perfect, but I believe it is better to have things in PMC than just on a journals website. So I am writing to all these journals to find out if they have any plans to deposit this material.

Freeing up the "fee for access" papers.
My final initial goal, and probably the most challenging, is to figure out ways to make the papers that are current "fee for access" available for free. If these were my papers, I suppose I could put many of the PDFs on my own web site. Perhaps I can do this for my father's publications (does the right to do this get passed down?). Of course, first I have to get the PDFs and it just seems weird to me to have to pay to get access to papers my father wrote. Another possibility is that the journals would let me pay an OA fee to free up these old papers. I am going to look into that although I cannot really afford it. A final possibility would be to get the papers into PMC without the journals explicit agreement. Perhaps because my father was a government employee, the copyright would allow depositing in PMC? I do not know.

So right now, the process is incomplete. I am actually learning a good deal about OA from looking into older papers rather than just all the new papers I tend to focus on. And hopefully in the process I can free up all of my father's papers so that his scientific legacy does not fade away as rapidly due to lack of access. And then next maybe I can focus on my grandfather's publications.

Anyway -- here is a list of my father's publications with links and/or comments on their availability.
  1. Simons SS Jr, Pumphrey JG, Rudikoff S, Eisen HJ. Identification of cysteine 656 as the amino acid of hepatoma tissue culture cell glucocorticoid receptors that is covalently labeled by dexamethasone 21-mesylate. J Biol Chem. 1987 Jul 15;262(20):9676-80. PMID: 3597435.Click here to read

  2. Cresteil T, Jaiswal AK, Eisen HJ. Transcriptional control of human cytochrome P1-450 gene expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin in human tissue culture cell lines. Arch Biochem Biophys. 1987 Feb 15;253(1):233-40. PMID: 3813564. Click here to read

  3. Eisen LP, Reichman ME, Thompson EB, Gametchu B, Harrison RW, Eisen HJ. Monoclonal antibody to the rat glucocorticoid receptor. Relationship between the immunoreactive and DNA-binding domain. J Biol Chem. 1985 Sep 25;260(21):11805-10. PMID: 3840164Click here to read

  4. Antakly T, Eisen HJ. Immunocytochemical localization of glucocorticoid receptor in target cells. Endocrinology. 1984 Nov;115(5):1984-9. PMID: 6208016. UPDATE - TO BE MADE AVAILABLE SOON ACCORDING TO HIGHWIRE PRESS.

  5. Harmon JM, Eisen HJ, Brower ST, Simons SS Jr, Langley CL, Thompson EB. Identification of human leukemic glucocorticoid receptors using affinity labeling and anti-human glucocorticoid receptor antibodies. Cancer Res. 1984 Oct;44(10):4540-7. PMID: 6331880Click here to read

  6. Reichman ME, Foster CM, Eisen LP, Eisen HJ, Torain BF, Simons SS Jr. Limited proteolysis of covalently labeled glucocorticoid receptors as a probe of receptor structure. Biochemistry. 1984 Oct 23;23(22):5376-84. PMID: 6391542

  7. Nebert DW, Eisen HJ, Hankinson O. The Ah receptor: binding specificity only for foreign chemicals? Biochem Pharmacol. 1984 Mar 15;33(6):917-24. Review. PMID: 6324804Click here to read

  8. Nebert DW, Brown DD, Towne DW, Eisen HJ. Association of fertility, fitness and longevity with the murine Ah locus among (C57BL/6N) (C3H/HeN) recombinant inbred lines. Biol Reprod. 1984 Mar;30(2):363-73. PMID: 6704471Click here to read

  9. Foster CM, Eisen HJ, Bloomfield CD. Covalent labeling of rat thymocyte and human lymphoid glucocorticoid receptor. Cancer Res. 1983 Nov;43(11):5273-7. PMID: 6577947Click here to read

  10. Karenlampi SO, Eisen HJ, Hankinson O, Nebert DW. Effects of cytochrome P1-450 inducers on the cell-surface receptors for epidermal growth factor, phorbol 12,13-dibutyrate, or insulin of cultured mouse hepatoma cells. J Biol Chem. 1983 Sep 10;258(17):10378-83. PMID: 6309801Click here to read

  11. Mariani G, Kortright KH, Eisen HJ, Adamson RH, Waldmann TA. A methodological approach for the study of protein synthesis by cell cultures in vitro. J Nucl Med Allied Sci. 1983 Jul-Sep;27(3):237-47. PMID: 6198498

  12. Simons SS Jr, Schleenbaker RE, Eisen HJ. Activation of covalent affinity labeled glucocorticoid receptor-steroid complexes. J Biol Chem. 1983 Feb 25;258(4):2229-38. PMID: 6687388. Click here to read

  13. Tukey RH, Hannah RR, Negishi M, Nebert DW, Eisen HJ. The Ah locus: correlation of intranuclear appearance of inducer-receptor complex with induction of cytochrome P1-450 mRNA. Cell. 1982 Nov;31(1):275-84. PMID: 6186383Click here to read

  14. Legraverend C, Hannah RR, Eisen HJ, Owens IS, Nebert DW, Hankinson O. Regulatory gene product of the Ah locus. Characterization of receptor mutants among mouse hepatoma clones. J Biol Chem. 1982 Jun 10;257(11):6402-7. PMID: 6896205Click here to read

  15. Nebert DW, Negishi M, Lang MA, Hjelmeland LM, Eisen HJ. The Ah locus, a multigene family necessary for survival in a chemically adverse environment: comparison with the immune system. Adv Genet. 1982;21:1-52. Review. PMID: 7036691. Available online for fee but not linked from Pubmed.

  16. Eisen HJ, Schleenbaker RE, Simons SS Jr. Affinity labeling of the rat liver glucocorticoid receptor with dexamethasone 21-mesylate. Identification of covalently labeled receptor by immunochemical methods. J Biol Chem. 1981 Dec 25;256(24):12920-5. PMID: 6895516Click here to read

  17. Hannah RR, Nebert DW, Eisen HJ. Regulatory gene product of the Ah complex. Comparison of 2,3,7,8-tetrachlorodibenzo-p-dioxin and 3-methylcholanthrene binding to several moieties in mouse liver cytosol. J Biol Chem. 1981 May 10;256(9):4584-90. PMID: 7217100Click here to read

  18. Stevens J, Eisen HJ, Stevens YW, Haubenstock H, Rosenthal RL, Artishevsky A. Immunochemical differences between glucocorticoid receptors from corticoid-sensitive and -resistant malignant lymphocytes. Cancer Res. 1981 Jan;41(1):134-7. PMID: 7448753Click here to read

  19. Nebert DW, Eisen HJ, Negishi M, Lang MA, Hjelmeland LM, Okey AB. Genetic mechanisms controlling the induction of polysubstrate monooxygenase (P-450) activities. Annu Rev Pharmacol Toxicol. 1981;21:431-62. Review. PMID: 7016012Click here to read

  20. Marković RD, Eisen HJ, Parchman LG, Barnett CA, Litwack G. Evidence for a physiological role of corticosteroid binder IB. Biochemistry. 1980 Sep 30;19(20):4556-64. PMID: 7426614. Available online to purchase though no listed in Pubmed.

  21. Eisen HJ. An antiserum to the rat liver glucocorticoid receptor. Proc Natl Acad Sci U S A. 1980 Jul;77(7):3893-7. PMID: 7001446Click here to read

  22. Hannah R, Simkins R, Eisen HJ. Synthesis of alpha-fetoprotein and albumin by fetal mouse liver cultured in chemically defined medium. Dev Biol. 1980 Jun 15;77(2):244-52. PMID: 6156873Click here to read

  23. Okey AB, Bondy GP, Mason ME, Kahl GF, Eisen HJ, Guenthner TM, Nebert DW. Regulatory gene product of the Ah locus. Characterization of the cytosolic inducer-receptor complex and evidence for its nuclear translocation. J Biol Chem. 1979 Nov 25;254(22):11636-48. PMID: 500663Click here to read

  24. Rechler MM, Eisen HJ, Higa OZ, Nissley P, Moses AC, Schilling EE, Fennoy I, Bruni CB, Phillips LS, Baird KL. Characterization of a somatomedin (insulin-like growth factor) synthesized by fetal rat liver organ cultures. J Biol Chem. 1979 Aug 25;254(16):7942-50. PMID: 468799Click here to read

  25. Simkins RA, Eisen HJ, Sparks JW, Glinsmann WH. Development of glucogenesis from galactose by fetal rat liver explants in organ culture. Dev Biol. 1978 Oct;66(2):353-60. PMID: 700252Click here to read

  26. Simkins RA, Eisen HJ, Glinsmann WH. Functional integrity of fetal rat liver explants cultured in a chemically defined medium. Dev Biol. 1978 Oct;66(2):344-52. PMID: 81156Click here to read

  27. Eisen HJ, Glinsmann WH. Maximizing the purification of the activated glucocorticoid receptor by DNA-cellulose chromatography. Biochem J. 1978 Apr 1;171(1):177-83. PMID: 646815Click here to read

  28. Eisen HJ, Glinsmann W. Partial purification of the glucocorticoid receptor from rat liver: a rapid, two-step procedure using DNA-cellulose. Biochem Biophys Res Commun. 1976 May 17;70(2):367-72. PMID: 180989Click here to read

  29. Eisen HJ, Ginsberg AL. Letter: Disulfiram hepatotoxicity. Ann Intern Med. 1975 Nov;83(5):673-5. PMID: 1200504. Back issues not currently available.

  30. Eisen HJ, Glinsmann W. Partial purification of glucocorticoid receptor from rat liver using DNA-cellulose. J Steroid Biochem. 1975 Jul;6(7):1171-3. PMID: 170470. AVAILABLE FOR FEE BUT NOT LINKED FROM PUBMED.

  31. Glinsmann WH, Eisen HJ, Lynch A, Chez RA. Glucose regulation by isolated near term fetal monkey liver. Pediatr Res. 1975 Jul;9(7):600-4. PMID: 125868. AVAILABLE FREE EVEN THOUGH MEDLINE DOES NOT HAVE LINK.

  32. Eisen HJ, Goldfine ID, Glinsmann WH. Regulation of hepatic glycogen synthesis during fetal development: roles of hydrocortisone, insulin, and insulin receptors. Proc Natl Acad Sci U S A. 1973 Dec;70(12):3454-7. PMID: 4357871Click here to read

  33. Eisen HJ, Glinsmann WH, Sherline P. Effect of insulin on glycogen synthesis in fetal rat liver in organ culture. Endocrinology. 1973 Feb;92(2):584-8. PMID: 4682869. Wrote to ask if they will become available.  UPDATE - TO BE MADE AVAILABLE SOON ACCORDING TO HIGHWIRE PRESS.

  34. Hellman DE, Eisen HJ, Goodman HM. The effects of hypophysectomy on phosphorylase activity in adipose tissue and muscle. Horm Metab Res. 1971 Sep;3(5):331-5. PMID: 4332655

  35. Eisen HJ, Goodman HM. Growth hormone and phosphorylase activity in adipose tissue. Endocrinology. 1969 Feb;84(2):414-6. PMID: 4303531. Wrote to ask if they will become available. UPDATE - TO BE MADE AVAILABLE SOON ACCORDING TO HIGHWIRE PRESS. 

Sunday, June 15, 2008

Connection between Video Games and Bioinformatics?

The Scientist Magazine has a nice piece on one of my favorite people in all of Science - Sean Eddy. In the article, they discuss how Sean is one of those bioinformatics folks who does not just hack together some code to do something but actually writes really good code for his programs. For those of you who do not know, Sean has made a whole collection of software tools for biologists (see his web site here). Perhaps the most widely used is HMMER, which is designed for making and using hidden markov models. But there are some other good ones he has put out. My favorite is Forester, which was made by Christian Zmasek in his lab and is supposed to be available here, although the site is not working right now (NOTE - Christian has posted a new link for it in the comments). I like this because, well, it is software for "phylogenomic" analysis.

Anyway - it is a nice article about Sean, especially the parts talking about how his background in video games contributed to his success in bioinformatics. Back to something I said above, Sean is without a doubt one of my favorite people in science. There are many reasons for this but here are a few.
  • He is very open with ideas.

    Once, at a conference, I gave a talk on this bizarre new pattern we had found when we were comparing the genomes of E. coli and V. cholerae. We had found that when we did genome-level alignments of these species there was an X-like pattern (see our paper on this here). Anyway, in the talk I said something to the effect of "we have no friggin idea how these X-like alignments could be generated" And Sean, I think in the quesiton session, pointed out that in another paper of ours we had seen what appeared to be symmetric inversions occurring around the origin of replication and that could create the X-alignment. And lo and behold he was right. We got the paper, but in a large part it was his push that got us looking at the inversions sooner than we would have.

  • He is very open with science.

    Most of Sean's work is on the open side of science. Open Source software. Open Access publications. Open everything. And I should point out that it was a talk by Sean that catalyzed my conversion into an Open Science supporter. I was attending a meeting in Ft. Lauderdale to discuss data release policies for genome projects. This meeting led to the "Ft Lauderdale Agreement" on data release, by the way. A the meeting there were many genomics players like Eric Lander and Francis Collins who were trying to push for not completely open data release policies where genome centers could release data but there would be constraints placed on the use of the data so that the genome centers would be the first to be able to publish genome scale analysis of an organisms genome sequence.

    At the time I was working at TIGR and I supported this notion of basically letting people search for a few genes of interest but preventing them from doing genome analyses. And then Sean got up and gave a talk and, well, blew my mind. I am sure I have notes somewhere from the meeting but basically what he said was - the genome projects whole point is to generate genome data for people to do genome-level analysis. So how on earth can we justify preventing exactly the type of analysis that the projects were designed to generate. He was not saying that we should not somehow protect the genome centers. What he was saying was that for the benefit of science, we need to find a way to allow people to do genome-level analyses immediately on the data. And he also said that the risks of releasing ones data with no restrictions are much less than everyone claims. I think he convinced many people that genome centers needed to open up their data release policies a bit more. And he convinced me.

    And so I went home from that meeting and decided to release the data from as many of my genome projects as I could, with NO restrictions (e.g., this is what we did with Tetrahymena). And also, this new found belief in openness helped pave the way for my conversion to being an Open Access publishing supporter.
Anyway, glad to see Sean getting positive press. It is well deserved. Now off to play some video games.

Future of Microbiology Funding at NSF?

Just got pointed to slides from Jim Collins' recent talk at the ASM Meeting in Boston (Collins is the Assistant Director of the NSF Directorate for Biological Sciences) . Unfortunately, I missed his talk but you can get a PDF file of his slides (with proprietary ones removed) and it makes for some interesting viewing.  

There are clearly some big changes planned at NSF for "microbial" research and there seems to be a plan to merge what used to be microbe focused projects into other programs such as NEON, Assembling the Tree of Life, and others. There do appear to be some "Microbe" specific programs that will still be around including a new one "Microbial Systems in the Biosphere" which seems to be replacing/merging with the Microbial Genomes and the Microbial Observatories program.  

Anyway ... it seems that some changes are afoot at NSF.  Since I missed the talk it is hard to tell what the general plan and big picture is here.  If anyone out there went to his talk or have seen other talks of his it would be useful if you could post some impressions here.

A million minds getting together can be confusing but might end up being really cool

Their is a possibly interesting paper in Genome Biology by Barend Mons et al: Calling on a million minds for community annotation in WikiProteins. I say possibly because the paper itself is quite confusing to me but the overall goal seems to be a cool concept. This group has created and is encouraging the use of "WikiProteins" a community annotation system for "community knowledge." Sounds a bit fuzzy? Well, reading the paper does not completely help. For example here is the abstract
WikiProteins enables community annotation in a Wiki-based system. Extracts of major data sources have been fused into an editable environment that links out to the original sources. Data from community edits create automatic copies of the original data. Semantic technology captures concepts co-occurring in one sentence and thus potential factual statements. In addition, indirect associations between concepts have been calculated. We call on a 'million minds' to annotate a 'million concepts' and to collect facts from the literature with the reward of collaborative knowledge discovery. The system is available for beta testing at webcite.
I got really lost reading this I confess. But I moved on since the overall concept seemed quite intriguing, even if I did not get it completely. But it did not get much clearer further on. For example consider their description of a "knowlet"

The future outlook to integrate data mining (for instance gene co-expression data) with literature mining, as formulated in the review by Jensen et al. [2], is at the core of what we aim for at the text mining/data mining interface. To support the capturing of qualitative as well as quantitative data of different natures into a light, flexible, and dynamic ontology format, we have developed a software component called Knowlets™. The Knowlets combine multiple attributes and values for relationships between concepts.

Scientific publications contain many re-iterations of factual statements. The Knowlet records relationships between two concepts only once. The attributes and values of the relationships change based on multiple instances of factual statements (the F parameter), increasing co-occurrence (the C parameter) or associations (The A parameter). This approach results in a minimal growth of the 'concept space' as compared to the text space (Figure 1).

OK ... I got lost every time I tried to read this in detail. I do think they could benefit greatly by translating their paper from the language used by people who work on text mining to a broader presentation.

But reading between the lines here, this is a new, apparently open access system to try and get community annotation for "Concepts" and for relationships among concepts in biological sciences. Those concepts could include a wide range of things, including genes, genomes, proteins, as well as more standard concepts like functions. Whatever this system is, it seems worth checking out.

I leave you with their ending:

Once widely used and augmented, this resource could become an open, yet quality assured and comprehensive, environment for collaborative reference and knowledge discovery.

Now that I can say I understand and it sounds good to me. If anyone out there has any more insight into this, please give your input.

Saturday, June 14, 2008

Deep microbes get all the love

Well, you know microbes must really be cool because Olivia Judson is blogging about them. You see, Olivia is also known as Dr. Tatiana. Judson's book "Dr. Tatiana's Sex Advice to All Creation" created and still creates a stir and helped make Olivia one of the go to people for discussions of the biology of sex and weird sex practices in the natural world. Now she has a blog (with what appear to be entries once a week) on the New York Times web site called "The Wild Side."

In the blogs of hers that I have read (note to New York Times --- your system of allowing access to the blog archive really sucks) I recall there being many references to microbes, even when the focus was not on microbes per se. And this week the whole darn blog is about them small little organisms. In this weeks blog, she writes about microbes living in the deep biosphere (some of my favorites) (see Meet the Intraterrestrials).

So - check out her blog. And encourage her to keep writing about microbes. We know they are cool but she can help convince all those others who are not yet microbe fans of this fact too.

Friday, June 13, 2008

Open Metagenomics: Selenium in the Oceans

Well, I have started previous an "Open Evolution" series here and now I am starting an "Open Metagenomics" series. I know, I have gotten grief from some out there (yes, you Rob Edwards - see comments here) about my support for somewhat non open things in metagenomics, so I am going to try and make up for that as much as possible.

In the first installment, I am pointing people to a new paper on PLoS Genetics "Trends in Selenium Utilization in Marine Microbial World Revealed through the Analysis of the Global Ocean Sampling (GOS) Project" by Yan Zhang, Vadim N. Gladyshev (hat tip to Katie Pollard for pointing out this paper).

In this paper the authors study selenium utilization using data from the first part of the Venter Global Ocean Survey (GOS) which was metagneomic sequencing from multiple samples - mostly surface ocean water.  The GOS data they use comes from the Rusch et al. paper in PLoS Biology (note for full disclosure ... I was an c0-author on this paper).  

There have been challenges with getting and using metagenomic data from other people's publications in the past and I note that the authors here obtained the data sets from CAMERA, a metagenomics database supported by the Moore Foundation.  I note - it is my support of this database that Rob Edwards gave me grief about since the database is not currently completely open (e.g., you need to register to use it and the software that runs it is not currently all open source). 

Anyway, they got the data from CAMERA, and then did a pretty comprehensive analysis to search for genes and features in the data that would be indicative of selenium utilization. Selenium is of great interest to many biologists for many reasons, including that it is required for the synthesis and function of Selenocysteine (Sec), which , if you do not know, goes occasionally by the nickname "The 21st amino acid"

Without going into all the details of the paper, the last paragraph sums up the major features
In this study, we report a comprehensive analysis of Sec utilization in marine microbial samples of the GOS expedition by characterizing the GOS selenoproteome. This is the first time that the microbial selenoprotein population is described in a global biogeographical context. Our analysis yielded the largest selenoprotein dataset to date, provided a variety of new insights into Sec utilization and revealed environmental factors that influence Sec utilization in the marine microbial world.
My favorite part of the paper is that they map some of the selenium related features onto the globe.  For example, in one figure they show the inferred selenoprotein "richness" in 
the different samples. (Selenoproteins are proteins that have selenocysteine in them).  Now I am sure there are many assumptions they made in leading to the inferences they have made about selenium utilization and I am also sure some of these will turn out to be a bad idea.  But to me, this paper is a good example of what researchers will be able to do with metagenomic data in the future.  Sitting at their computers anywhere in the world, researchers can now ask questions about the distribution patterns of functions in microbes in the world.  Pretty cool.  And the more open we are with the papers, the tools, and the data, the more likely this type of work is to spread.

The figures are from the paper and I am permitted to use them here because they were published under a Creative Commons license that allows anyone to use them as long as the source is cited. The source is Zhang Y, Gladyshev VN (2008) Trends in Selenium Utilization in Marine Microbial World Revealed through the Analysis of the Global Ocean Sampling (GOS) Project. PLoS Genet 4(6): e1000095. doi:10.1371/journal.pgen.1000095 

Wednesday, June 11, 2008

An Open Access pioneer - Trent Reznor

Normally, everything I write about here is at least indirectly connected to science in some way. However, today I am drifting into the world of music. The New York Times had an article a few days ago about Trent Reznor (Trent Reznor’s Frustration and Fury - Take It. It’s Free). Trent, the brains behind the band Nine Inch Nails (full disclosure - I am a fan of his music), has been railing against the constraints of the music industry for year.

And now he is going even further and in essence putting his music into the public domain as much as possible (see his web site for more detail). For example
"Mr. Reznor even posts online all the raw digital tracks from Nine Inch Nails albums for anyone to remix. “I’m done with them,” he said. “Why not?”
And he is doing this even though the $$$ for producing his music does not come from the government. He does it in part because he wants his ideas and music to spread and he wants to contribute to musical development. There are obvious parallels between what he (and others) are doing in music and those who develop Open Source software and those who release their data and publications to be as free as possible. I know I am not the first to discuss this, but just thought I would put it out there.

Wanted - Summer Intern in Microbial Genomics/Diversity at the Gordon and Betty Moore Foundtion

The Marine-Microbiology Initiative at the Gordon and Betty Moore Foundation is looking a person to work there for the summer. This is
"a short-term opportunity for an advanced undergraduate or graduate student who would enjoy delving into the genes and genomes of the microbes sequenced as part of the Microbial Genome Sequencing Project (a.k.a the "Moore 155")."
For further details and links see the GBMF job ad. Note applications are due June 16, 2008. Here is more detail on what they are looking for:

Since 2004, the Microbial Genome Sequencing Project (MGSP) funded by the Marine Microbiology Initiative has produced the complete genome sequences of a diverse array of Bacteria and Archaea. To date, the genomes of over 130 microbes have been sequenced, annotated using automated computer algorithms, and deposited in public databases. The primary objective for the internship will be to research and synthesize information about the genome content, isolation habitats, and ecology for these microorganisms.

Specific goals include:

  • -Synthesize important new discoveries from scientific publications resulting from the MGSP
  • -Compare genomes to seek novel patterns of gene content as a function of organism’s habitat and physiology
  • -Build 16S rRNA phylogenetic trees for major Bacterial and Archaeal clades for inclusion on the website
  • -Research the primary scientific literature relating to viruses (phage) that infect MGSP microorganisms to investigate the influence of phage on microbial evolution and ecology

Preferred Qualifications/Skill Set:

  • -Advanced biological sciences or computer sciences undergraduate or graduate student preferred
  • -Strong research, writing, and oral communication skills
  • -Strong interest and knowledge of microbial evolution and ecology
  • -Experience working with microbial genomes or gene sequences preferred

Chris Smither on Darwin and Intelligent Design

Entertaining little song by Chris Smither on Evolution/Darwin/Intelligent Design. Scroll to the 2:00 time point if you cannot wait.
Thanks to Iddo Friedberg for the tip.

Tuesday, June 10, 2008

Good luck Chris Gunter ...

One of my favorite journal editors is moving on.  Chris Gunter, who has been one of the genetics and genomics editors at Nature is moving to be the "Director of Research Affairs at the HudsonAlpha Institute for Biotechnology." She has been a big promoter of "free access" to articles within Nature and was at least in part responsible for (if not the major person behind) the fact that many genomics papers at Nature were freely available to all (note they were not always fully OA publications but at least they were free, which was more than many other journals, even non profit ones were doing).

As for what Chris will do at HudsonAlpha, the press release says she "will work closely with Dr. Richard M. Myers, HudsonAlpha director, to raise awareness about HudsonAlpha and its research programs on a national level." RIck was the person who helped push me to formalize my ideas behind "phylogenomics" many years ago when we were both at Stanford and so now two of my favorite genomics folks will be in Alabama. I guess HudsonAlpha is a place to keep an eye on ...

Getting John Henry and his hammer into a scientific paper

Gotta love a scientific paper that quotes John Henry stories. In Andy Ellington's primer on ribozyme evolution (PLoS Biology - Man versus Machine versus Ribozyme) he leads off with

The steam drill was on the right hand side,

John Henry was on the left,

Says before I let this steam drill beat me down,

I'll hammer myself to death”—The Ballad of John Henry (American, traditional)

His point here is to talk about man versus machine and to then discuss the recent article in PLoS Biology on a "Darwinian Machine" which I wrote about previously. (I think he is also making a bit of a play on words with the hammerhead ribozyme, but I am not sure). Anyway, Ellignton's article is worth checking out. I especially like the ending

Machine-based continuous evolution should be the best of all worlds, combining man's mental ability to chart the future with automated control of selection stringency with the still unpredictable mode and tempo of evolution's relentless drive.

Figure from Ellington's PLoS Biology paper. I can put it here because it is a fully Open Access paper using a broad Creative Commons license. All I have to do is cite the source. And so I am. Andy Ellington. PLoS Biol 6(5): e132 doi:10.1371/journal.pbio.0060132

Figure reportedly by Angel Syrett (see comments).

Monday, June 09, 2008

Plant kin recognition? (Caution - Anthropocentrism ahead)

A fascinating story in the New York Times today on kin recognition in plants (see Plants Found to Show Preferences for Their Relatives ).

They report
The sea rocket, researchers report, can distinguish between plants that are related to it and those that are not. And not only does this plant recognize its kin, but it also gives them preferential treatment.

Dodder is unable to grow its own roots or make its own sugars using photosynthesis, the process used by nearly all other plants. As a result, scientists knew that after sprouting from seed, the plant would fairly quickly need to begin growing on and into another plant to extract the nutrients needed to survive.

But even the scientists studying the plant were surprised at the speed and precision with which a dodder seedling could sense and hunt its victim. In time-lapse movies, scientists saw dodder sprouts moving in a circular fashion, in what they discovered was a sampling of the airborne chemicals released by nearby plants, a bit like a dog sniffing the air around a dinner buffet.

The notion that plants sense and respond to their surroundings is apparently controversial. Or, maybe a better way to put it is, the attempts to compare plant to animal neural functions is controversial. So much so that many plant scientists got together to say enough is enough

Thirty-six authors from universities that included Yale and Oxford were exasperated enough to publish an article last year, “Plant Neurobiology: No Brain, No Gain?” in the journal Trends in Plant Science. The scientists chide the new society for discussing possibilities like plant neurons and synapses, urging that the researchers abandon such “superficial analogies and questionable extrapolations.”

I personally think there is an enormous amount of anthropocentrism here. Sure, plants may not have true brains. But even though many people like to think of animals in general and humans in particular as the be all end all of evolution, last time I checked, plants have been evolving for a long time. And there is no reason to think that they do not have all sorts of cool and wacky ways to sense and respond to the world around them.

The same anthropocentric point of view has led scientists to grossly underestimate the complexity of phenomena in microbes too. Microbes in fact can sense and respond to kin, they can count, they can tell time, they have immune systems. In other words, whether small or large, furry or not, simple or complex (in appearance) lots of cool things have evolved in lineages that do not lead up to humans.

Well, everyone. As we continue to delve into the biology of non animals more deeply, we are going to find all sorts of cool things out there. And yes, some of it will be even more complex and interesting and wacky than what we see in animals.

For other stuff on this story see

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