Environmental Shotgun Sequencing: Its Potential and Challenges for Studying the Hidden World of Microbes. PLoS Biol 5(3): e82

I am posting here my recent paper that just came out in PLoS Biology on Environmental Shotgun Sequencing. With PLoS's Creative Commons license I am allowed to do this, which makes me happy. The citation is Eisen JA (2007) Environmental Shotgun Sequencing: Its Potential and Challenges for Studying the Hidden World of Microbes. PLoS Biol 5(3): e82 doi:10.1371/journal.pbio.0050082

Environmental Shotgun Sequencing: Its Potential and Challenges for Studying the Hidden World of Microbes

Jonathan A. Eisen

Citation: Eisen JA (2007) Environmental Shotgun Sequencing: Its Potential and Challenges for Studying the Hidden World of Microbes. PLoS Biol 5(3): e82 doi:10.1371/journal.pbio.0050082

Published: March 13, 2007

Copyright: © 2007 Jonathan A. Eisen. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abbreviations: ESS, environmental shotgun sequencing; PCR, polymerase chain reaction; rRNA, ribosomal RNA

Jonathan A. Eisen is at the University of California Davis Genome Center, with joint appointments in the Section of Evolution and Ecology and the Department of Medical Microbiology and Immunology, Davis, California, United States of America. Web site: http://phylogenomics.blogspot.com. E-mail:jaeisen@ucdavis.edu

Series Editor: Simon Levin, Princeton University, United States of America

This article is part of the Oceanic Metagenomics collection in PLoS Biology. The full collection is available online at http://collections.plos.org/plosbiology/gos-2007.php.

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Since their discovery in the 1670s by Anton van Leeuwenhoek, an incredible amount has been learned about microorganisms and their importance to human health, agriculture, industry, ecosystem functioning, global biogeochemical cycles, and the origin and evolution of life. Nevertheless, it is what is not known that is most astonishing. For example, though there are certainly at least 10 million species of bacteria, only a few thousand have been formally described [1]. This contrasts with the more than 350,000 described species of beetles [2]. This is one of many examples indicative of the general difficulties encountered in studying organisms that we cannot readily see or collect in large samples for future analyses. It is thus not surprising that most major advances in microbiology can be traced to methodological advances rather than scientific discoveries per se.

Examples of these key revolutionary methods (Table 1) include the use of microscopes to view microbial cells, the growth of single types of organisms in the lab in isolation from other types (culturing), the comparison of ribosomal RNA (rRNA) genes to construct the first tree of life that included microbes [3], the use of the polymerase chain reaction (PCR) [4] to clone rRNA genes from organisms without culturing them [5–7], and the use of high-throughput “shotgun” methods to sequence the genomes of cultured species [8]. We are now in the midst of another such revolution—this one driven by the use of genome sequencing methods to study microbes directly in their natural habitats, an approach known as metagenomics, environmental genomics, or community genomics [9].

Table 1.

Some Major Methods for Studying Individual Microbes Found in the Environment

In this essay I focus on one particularly promising area of metagenomics—the use of shotgun genome methods to sequence random fragments of DNA from microbes in an environmental sample. The randomness and breadth of this environmental shotgun sequencing (ESS)—first used only a few years ago [10,11] and now being used to assay every microbial system imaginable from the human gut [12] to waste water sludge [13]—has the potential to reveal novel and fundamental insights into the hidden world of microbes and their impact on our world. However, the complexity of analysis required to realize this potential poses unique interdisciplinary challenges, challenges that make the approach both fascinating and frustrating in equal measure.

Who Is Out There? Typing and Counting Microbes in the Environment

One of the most important and conceptually straightforward steps in studying any ecosystem involves cataloging the types of organisms and the numbers of each type. For a long time, such typing and counting was an almost insurmountable problem in microbiology. This is largely because physical appearance does not provide a valid taxonomic picture in microbes. Appearance evolves so rapidly that two closely related taxa may look wildly different and two distantly related taxa may look the same. This vexing problem was partially overcome in the 1980s through the use of rRNA-PCR (Table 1). This method allows microorganisms in a sample to be phylogenetically typed and counted based on the sequence of their rRNA genes, genes that are present in all cell-based organisms. In essence, a database of rRNA sequences [14,15] from known organisms functions like a bird field guide, and finding a rRNA-PCR product is akin to seeing a bird through binoculars. Rather than counting species, this approach focuses on “phylotypes,” which are defined as organisms whose rRNA sequences are very similar to each other (a cutoff of >97% or >99% identical is frequently used). The ability to use phylotyping to determine who was out there in any microbial sample has revolutionized environmental microbiology [16], led to many discoveries [e.g., 17], and convinced many people (myself included) to become microbiologists.

The selective targeting of a single gene makes rRNA-PCR an efficient method for deep community sampling [18]. However, this efficiency comes with limitations, most of which are complemented or circumvented by the randomness and breadth of ESS. For example, examination of the random samples of rRNA sequences obtained through ESS has already led to the discovery of new taxa—taxa that were completely missed by PCR because of its inability to sample all taxa equally well (e.g., [19]). In addition, ESS provides the first robust sampling of genes other than rRNA, and many of these genes can be more useful for some aspects of typing and counting. Some universal protein coding genes are better than rRNA both for distinguishing closely related strains (because of third position variation in codons) and for estimating numbers of individuals (because they vary less in copy number between species than do rRNA genes) [10]. Perhaps most significantly, ESS is providing groundbreaking insights into the diversity of viruses [20,21], which lack rRNA genes and thus were left out of the previous revolution.

Certainly, many challenges remain before we can fully realize the potential of ESS for the typing and counting of species, including making automated yet accurate phylogenetic trees of every gene, determining which genes are most useful for which taxa, combining data from different genes even when we do not know if they come from the same organisms, building up databases of genes other than rRNA, and making up for the lack of depth of sampling. If these challenges are met, ESS has the potential to rewrite much of what we thought we knew about the phylogenetic diversity of microbial life.

What Are They Doing? Top Down and Bottom Up Approaches to Understanding Functions in Communities

A community is, of course, more than a list of types of organisms. One approach to understanding the properties and functioning of a microbial community is to start with studies of the different types of organisms and build up from these individuals to the community. Ideally, to do this one would culture each of the phylotypes and study its properties in the lab. Unfortunately, many, if not most, key microbes have not yet been cultured [22]. Thus, for many years, the only alternative was to make predictions about the biology of particular phylotypes based on what was known about related organisms. Unfortunately, this too does not work well for microbes since very closely related organisms frequently have major biological differences. For example, Escherichia coli K12 and E. coli O157:H7 are strains of the same species (and considered to be the same phylotype), with genomes containing only about 4,000 genes, yet each possesses hundreds of functionally important genes not seen in the other strain [23]. Such differences are routine in microbes, and thus one cannot make any useful inferences about what particular phylotypes are doing (e.g., type of metabolism, growth properties, role in nutrient cycling, or pathogenicity) based on the activities of their relatives.

These difficulties—the inability to culture most microbes and the functional disparities between close relatives—led to one of the first kinds of metagenomic analyses, wherein predictions of function were made from analysis of the sequence of large DNA fragments from representatives of known phylotypes. This approach has provided some stunning insights, such as the discovery of a novel form of phototrophy in the oceans [24]. However, this large insert approach has the same limitation as predicting properties from characterized relatives—a single cell cannot possibly represent the biological functions of all members of a phylotype.

ESS provides an alternative, more global way of assessing biological functions in microbial communities. As when using the large insert approach, functions can be predicted from sequences. However, in this case the predicted functions represent a random sampling of those encoded in the genomes of all the organisms present. This approach has unquestionably been wildly successful in terms of gene discovery. For example, analysis of ESS data has revealed novel forms of every type of gene family examined, as well as a great number of completely novel families (e.g., [25]). However, there is a major caveat when using ESS data to make community-level inferences. Ecosystems are more than just a bag of genes—they are made up of compartments (e.g., cells, chromosomes, and species), and these compartments matter. The key challenge in analyzing ESS data is to sort the DNA fragments (which are usually less than 1,000 base pairs long relative to genome sizes of millions or billions of bases) into bins that correspond to compartments in the system being studied.

A recent study by myself and colleagues illustrates the importance of compartments when interpreting ESS data. When we analyzed ESS data from symbionts living inside the gut of the glassy-winged sharpshooter (an insect that has a nutrient-limited diet), we were able to bin the data to two distinct symbionts [26]. We then could infer from those data that one of the symbionts synthesizes amino acids for the host while the other synthesizes the needed vitamins and cofactors. Modeling and understanding of this ecosystem are greatly enhanced by the demonstration of this complementary division of labor, in comparison to simply knowing that amino acids, vitamins, and cofactors are made by “symbionts.”

How does one go about binning ESS data? A variety of approaches have been developed, some of which are described in Table 2. In considering the different binning methods and their limitations, the first question one needs to ask is, what are we trying to bin? Is it fragments from the same chromosome from a single cell, which would be useful for studying chromosome structure? If so, then perhaps genome assembly methods are the best. What if instead, as in the sharpshooter example, we are trying to have each bin include every fragment that came from a particular species, knowledge which may be useful for predicting community metabolic potential? If the level of genetic polymorphism among individual cells from the same species is high, then genome assembly methods may not work well (the polymorphisms will break up assemblies). A better approach might be to look for species-specific “word” frequencies in the DNA, such as ones created by patterns in codon usage. The challenge is, how do we tune the methods to find the right target level of resolution? If we are too stringent, most bins will include only a few fragments. But if we are too relaxed, we will create artificial constructs that may prove biologically misleading, such as grouping together sequences from different species. To make matters more complex, most likely the stringency needed will vary for different taxa present in the sample.

Table 2.

Methods of Binning

Another critical issue is the diversity of the system under study. Generally, binning works better when there are few different phylotypes present, all of which are distantly related and form discrete populations. This is why binning works well for the sharpshooter system and other relatively isolated, low diversity environments. Binning increases in difficulty exponentially as the number of species increases: the populations and species start to merge together, and the populations get more and more polymorphic and variable in relative abundance (such as in the paper about the Global Ocean Sampling expedition in this issue [27]). Further complicating binning is the phenomenon of lateral gene transfer, where genes are exchanged between distantly related lineages at rates that are high enough that random sampling of a genome will frequently include genes with multiple histories.

Despite these challenges, I believe we can develop effective binning methods for complex communities. First, we can combine different approaches together, such as using one method to sort in a relaxed manner and then using another to subdivide the bins provided by the first method. Second, we can incorporate new approaches such as population genetics into the analysis [28]. In addition, the lessons learned here can be applied to other aspects of metagenomics (e.g., the counting and typing discussed above) and provide insights into the nature of microbial genomes and the structure of microbial populations and communities.

Comparative Metagenomics

So far, I have discussed issues relating mostly to intrasample analysis of ESS data. However, the area with perhaps the most promise involves the comparative analysis of different samples. This work parallels the comparative analysis of genomes of cultured species. Initial studies of that type compared distantly related taxa with enormous biological differences. What has been learned from these studies pertains mostly to core housekeeping functions, such as translation and DNA metabolism, and to other very ancient processes [29,30]. It was not until comparisons were made between closely related organisms that we began to understand events that occurred on shorter time scales, such as selection, gene transfer, and mutation processes [31]. Similarly, the initial comparisons of ESS data involved comparisons of wildly different environments [32], yielding insights into the general structure of communities. But as more comparisons are made between similar communities [33,34], such as those sampled during vertical and horizontal ocean transects [27,35–37], we will begin to learn about shorter time scale processes such as migration, speciation, extinction, responses to disturbance, and succession. It is from a combination of both approaches—comparing both similar and very divergent communities—that we will be able to understand the fundamental rules of microbial ecology and how they relate to ecological principles seen in macro-organisms.

Conclusions

In promoting some of the exciting opportunities with ESS, I do not want to give the impression that it is flawless. It is helpful in this respect to compare ESS to the Internet. As with the Internet, ESS is a global portal for looking at what occurs in a previously hidden world. Making sense of it requires one to sort through massive, random, fragmented collections of bits of information. Such searches need to be done with caution because any time you analyze such a large amount of data patterns can be found. In addition, as with the Internet, there is certainly some hype associated with ESS that gives relatively trivial findings more attention than they deserve. Overall, though, I believe the hype is deserved. As long as we treat ESS as a strong complement to existing methods, and we build the tools and databases necessary for people to use the information, it will live up to its revolutionary potential.

Acknowledgments

I thank Simon Levin, Joshua Weitz, Jonathan Dushoff, Maria-Inés Benito, Doug Rusch, Aaron Halpern, and Shibu Yooseph for helpful discussions, and Melinda Simmons, Merry Youle, and three anonymous reviewers for helpful comments on the manuscript. The writing of this paper was supported by National Science Foundation Assembling the Tree of Life Grant 0228651 to Jonathan A. Eisen and by the Defense Advanced Research Projects Agency under grants HR0011-05-1-0057 and FA9550-06-1-0478.

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Venter Global Ocean Voyage Press Conference

For those interested in metagenomics, microbial diversity and ocean microbiology, there will be a press conference tomorrow run by the Venter Institute relating to a series of papers (I am an author on some) coming out in PLoS Biology. The papers relate to Venter's Global Ocean Voyage - sailing around the world collecting microbial samples. These were then used for environmental shotgun sequencing and the papers discuss various aspects of analzying the data.

Say what you want about metagenomics, and Craig and genomics, if you are a critic. But (1) read the papers, (2) give Venter some credit for publishing in an Open Access journals unlike many of the so called "public" genome effort folks who generally only pretend to support public/open access to anything.

Here is a link to view the live web cast of the PloS Biology GOS Expedition publication press conference. The press conference will be held tomorrow March 13 from 10-11 a.m. EST. After tomorrow an archive of the web cast will be hosted on the JCVI web site.

The papers are now live on the PLoS Biology Web Site.

The Global Ocean Sampling Collection can be found here.

My essay on Environmental Shotgun Sequencing can be found here.

Controversy over BP deal at Berkeley

Apparently, there is a building controversy within Berkeley over the recently announced $500 million dollar deal with BP on a biofuel program. A series of articles (e.g., here) in the SF Chronicle have been reporting on the deal and the more recent ones are starting to document some potential issues with the deal. Also see the Berkeley Daily Planet commentary.

From the Chron:

UC Berkeley's $500 million energy research deal with oil giant BP took a pounding at a faculty forum Thursday, with a host of speakers critical of the unprecedented partnership -- some bitingly so.

I am quite interested in this because although I think it is great that Berkeley/LBL are going to now be moving big time into biofuels research, I have heard and read a variety of things regarding this deal that make one want to look at it more carefully. Some of the grumblings may be related to the standard anti-GMO opinions pervasive in Berkeley, but some of them may be more significant. For example when I gave a talk at Berkeley a few weeks ago, I asked as many people as I could why Berkeley picked U. Illinois to be their agricultural partner on the project and not Davis. And the answer was basically always the same - supposedly people at Berkeley were told by BP that Davis could not be involved because Davis had recently singed a collaborative agreement with Chevron over biofuels research.

Now folks at Berkeley are welcome to choose whomever they want to be involved in the project. But if they were told by BP that Davis could not be involved, that suggests academic freedom was tossed out the window. This thing is - I have been having a hard time getting any straight answers from people involved in the LBL/Berkeley side of things. So I had forgotten about the whole thing when someone sent me a link to the Chron story. What really caught my attention is the quote from Paul Rabinow in the article:

Anthropology Professor Paul Rabinow cited the 1998-2003 research deal between Swiss biotech firm Novartis and Cal's Department of Plant and Microbial Biology. That deal, which provided for $5 million a year from 1998 to 2003, was intended to develop genetically engineered foods. It sparked campus protests and was criticized at the time by faculty members who felt it was implemented without collegial debate.

"The way the university handled it was completely, recklessly stupid," Rabinow said.

The same mistakes are being repeated with the BP deal, he said.

"It should have been transparent, there should have been consultation," he said. "This is silly. You should have given us more time to debate this."

I met Paul at a workshop at Berkeley on the field of Synthetic Biology and he struck me as one of the most sensible people in the crowd even though he was not directly involved in Synthetic Biology research. He gave a talk at the meeting that was really spectacular (I think you see the talk here). Since newspaper articles do not always get the whole story correct, I am not certain how accurately they represent Paul's real concerns regarding the BP deal.

But from the article it sounds like the Berkeley and LBL administration may not have consulted the faculty broadly on the nature of the deal. That would be a bad thing since such secrecy is, as Rabinow implied, not the right way to get community support. In addition, it sounds like some of the people involved in the project have let the large amount of money go to their heads (one faculty member was reported to have said that Berkeley "researchers can't afford to fail on a project of such magnitude" as though it was the amount of money that determined whether one should do a good job on something, which is silly).

So I guess the question that is unresolved is - did Berkeley and LBL compromise their principles for a pot of gold? I do not know but I hope they get moving in front of this really rally fast and (1) make sure the deal is on the up and up and (2) become more open about the whole thing. This is particularly important because I think LBL and Berkeley could become world leaders in biofuels research. But they could also cause biofuels research to end up being treated like all genetic engineering work if they are not careful. And that would be a bad thing since if done right, biofuels have enormous potential. Here's hoping Berkeley/LBL/BP change tactics, and get rid of the whole secrecy thing and move every detail of the project into the open.

A webcast of the meeting is here.

Gagging of scientists

From an article in the SF Chronicle

The federal agency responsible for protecting Arctic polar bears has
barred two Alaska scientists from speaking about polar bears, climate
change or sea ice at international meetings in the next few weeks, a move
that environmentalists say is censorship.

I try in this blog to not get involved in too many political issues - except of course those related to Open Access publishing. I do this because I think Open Access needs support from all sides of the political spectrum and because there are many things about Open Access that are consistent with political views throughout the spectrum. However, the treatment of scientists by the Federal Government just keeps getting worse and worse. Stem Cells. Evolution. Global Warming. Food science. And so on. The feds seem to think that scientific research is another form of spin. Scientists should read this chronicle article and really should start fighting back more.

So from now on I am adding intellectual freedom for scientists as another topic area of my blog.

OH, and thanks to Melinda Simmons at the Moore Foundation for suggesting this for my blog

Fun at Bodega Bay (U. C. Davis' Marine Lab and site of the U. C. Davis workshop in Applied Phylogenetics)

Well, gave a talk today out at Bodega Bay as part of the U. C. Davis workshop in Applied Phylogenetics. I talked about my favorite topic, phylogenomics (always good to preach, even to the converted) and enjoyed meeting the students and talking to the other faculty. But the main resons for this blog --- Davis' marine lab on a nice day is simply spectacular. If I ever teach a workshop I am going to try and hold it there.

Why I am ashamed to have a paper in Science

So I just had a paper published in Science last week. In many ways, it has all the makings of one of those papers I should be really proud of. First, it represents a collaboration with my undergraduate advisor, Colleen Cavanaugh, the person who inspired me to go to graduate school and who got me interested in microorganisms, which I have worked on ever since (I published my first scientific paper on work I did in her lab). The paper is on one of the coolest biological systems on the planet - bacterial symbionts of deep sea animals that allow these animals to function much like plants (they use chemosynthesis in much the same way plants use photosynthesis). Studies of the deep sea and of chemosynthesis are important for understanding the origin and evolution of life, for understanding global carbon cycles, for understanding the rules by which symbioses evolve and much more. And on top of all of this, the paper reports the sequencing and analysis of the complete genome of one of these symbionts (that from the clam Calyptogena magnifica) - and one of my main areas of research is on the evolution of the genomes of symbionts. And, the genome was sequenced at the Joint Genome Institute, where I now have an Adjunct Position and am working with extensively. All sounds good right? And, I should be happy to get a paper in Science too, right?

Actually, in reality, I am not pleased with how this paper has turned out. This is really due to two things. First, my collaborators failed to keep me in the loop that the paper was accepted in Science. Thus I did not find out about the paper until I did a google search for some other reason and noticed this Deep-Sea News Blog which had a story, well, about the paper in Science. It would of course have been nice to know the paper was accepted and coming out. It would have been even better to have seen the page proofs, which might have given me the chance to catch some little and not so little mistakes (e.g., the paper claims that this species has the largest genome of any intracellular symbiont sequenced to date - which is unfortunately not true). Now, admittedly I was out sick for a while and maybe my collaborators just did not want to bother me with this information. More likely- people were just very busy - and this just slipped through the cracks.

But you know - it is a Science paper. I should be happy however it came into being right? Well, no. Completely and thoroughly wrong. You see, I do not support publishing things in Science. I object because Science is not an Open Access journal. I tried and tried to get Irene Newton the first author to submit this to another journal. But in the end, she did the brunt of the work, and thus she and her advisor, Colleen, got to pick the place. And in the time since Irene submitted the paper, I have become even more miltant against publishing in such non Open Access journals. Publishing in a non Open Access journal like Science make me feel icky in every way. In addition, by choosing to publish the paper there but not elsewhere, the field of deep sea symbionts may have been hurt rather than helped.

How could a Science paper hurt the field? Well, for one, Science with its page length obsession forced Irene to turn her enormous body of work on this genome into a single page paper with most of the detail cut out. I do not think a one page paper does justice to the interesting biology or to her work. A four page paper could have both educated people about the ecosystems in the deep sea, about intracellular symbionts in general, and about this symbiosis in particular. The deep sea is wildly interesting, and also at some risk from human activities. This paper could have been used to do more than just promote someone's resume (which really is the only reason to publish a one page page in Science).

But of course, even more importantly, anyone without a subscription to Science, well, they can't even read the paper. And AAAS gets to decide what happens to the text and figures in the future. So - count this as one of my papers I am not really proud of. I love that I helped my Undergrad. advisor and one of my favorite people in the world do this work. But by it not being in an Open Access journal, I have unfortunately contributed to a system that I think is bad for the world. And I just fell icky.







Some news stories and blogs are coming out on the paper:

• Christian Science Monitor briefings
• UPI story
  
• Deep-Sea News Blog
• UC Davis "Egghead" Blog about this
• The Voltage Gate blog
  

Below I have embedded a video of a dissection of what I think was a deep sea Calyptogena, just for the fun of it.




This was taken during a deep sea cruise I managed to get on. For mroe detail on this cruise, see the NOAA Ocean Explorers site here.

Tour of California comes to town

Here are some pics and videos of the Amgen Tour of California as it left Davis, CA on Road 102.

























































































Here are some videos too.

Badges - do scientists need any stinking badges?

Thanks to garry Myers at TIGR for pointing this one out.

I just got done browsing through the ScienceScouts Site. This comes from the Science Creative Quarteryly which I have never heard of before and seems to be some sort of blog. If anyone knows more about it let me know.

Anyway, the ScienceScouts site has "badges" like Boy Scout Badges, but for scientists.

Examples include:

"The "inordinately fond of invertebrate" badge.
In which the recipient professes an arguably unhealthy affinity for things of this category. (http://scq.ubc.ca/sciencescouts/index.html#30)"

and

The "I blog about science" badge.
In which the recipient maintains a blog where at least a quarter of the material is about science. Suffice to say, this does not include scientology.

(http://scq.ubc.ca/sciencescouts/index.html#6)




which of course, I am awarding to myself.

Garry suggests that I get them to add an "I support PLOS" badge, which I am going to do ... People should check it out and award badges to unsuspecting individuals

Tony Hey visits U. C. Davis

Just got back from a dinner with Tony Hey, who was visiting UC. Davis to give a talk and meet with various people. Hey is currently VP for technical computing at some place called Microsoft. Hey has done some pretty interesting things in his career but what I know him from is his time as the head of the "E-science" initiative in the UK. Before I blather on about this ... check out Timo Hannay's blog about Hey's visit to Nature which has a pseudo outline of his talk he gave there.

It is interesting to see Microsoft getting into collaborative science --- I hope they stay serious about it because we need more "top down" types of efforts are big places like Microsoft. Whether Microsoft could make much money out of contributing to science I do not know, but if they put 1/1000 of the effort into this as they do into games and Office, science would almost certainly benefit. Many years ago when I was at TIGR, some Microsoft folks came to visit (when genome-stocks were going crazy) and expressed an interest in getting more involved in bioinformatics and genomics. Looks like that did not go anywhere. Maybe now is the time to try to get them doing this again?

I know Microsoft is viewed as Evil incarnate by many academics but hey (no pun intended), given the cool stuff being done by the Gates Foundation in various areas of science, maybe Microsoft will move a little more into science if only to support Gates Foundation efforts. Certainly, Tony Hey's background suggests that they have the potential to do some interesting stuff.

Davis Wetlands - Beatiful Place, but Bizarrely Closed to Visitors most of the Winter

If you live near Davis you should check out the Davis Wetlands - a pseudopreserve over by the landfill. Its got amazing birds and some nice trails to walk around on. The only problem is, in the Winter, when it is wettest and the birding is best, the Wetlands is closed almost all the time. It is only open to the public for a few hours on Mondays. In addition, there are signs all over on most of the trails saying they are closed to vistors. What gives?

I found this to be completely lame and so I wrote to the Davis government about it

To whom it may concern

I am writing to ask some questions regarding usage policies for the Davis Wetlands. I think Davis Wetlands is one of the gems of this city. I have taken my now 20 month old daughter there many times to walk around and see the birds and animals and get a nice park-like experience. I am writing because I am concerned about the severe usage restrictions at the Davis Wetlands.

First, in the Winter months, the park is only open on Mondays which means those of us who work regular hours cannot use the park. I am wondering if there is some reason why the park is not open all days of the week in Winter and also how Monday was chosen as the day to be open. I would like to recommend that in Winter the park be open on at least one weekend day.

Second, I am wondering why such a large fraction of the park has signs that say "Park Employee's Only" or something like that. These are all over the park on many of the levees and they mean that very little of the park can be seen by non employees. I am wondering why so much is off limits and whether there are any plans to expand public access. If not, I would recommend you do so.

The response I got was quick, although not what I expected ...

Dear Mr. Eisen,
Thank you for contacting the Davis Public Works Department.
Your message has been forwarded to Mr. John McNerney, Wildlife
Resource Specialist, in-charge of the Davis Wetlands. If you wish to
contact Mr. McNerney, his direct line is (530) 757-5680.

If you have any questions, please call (530) 757-5686 or e-mail us
at: pwweb@cityofdavis.org

Thanks!
Maria Briilantes
Office Assistant

And then McNerny replied the next day

Dear Mr. Eisen,

Thanks you for inquiring about the access times for the Davis
Wastewater Treatment Wetlands. As you are aware, the current access
periods are:
Feb 15 - August 31 (summer)-- 7 days per week 7am to 1pm.
Sept 1 - Feb 14 (winter) -- Mondays only from 7am to 1pm.

In addition to the normal access times, a docent led tour is offered
the first Saturday of the month from 9 to 11am (during summer hours) and
from 3 to 5pm (winter).

The current access times were negotiated during the drafting of the
original purchase agreement with the neighboring landowners (Conaway
Ranch Conservancy). These periods and times were set to reduce Wetlands
visitor conflicts with adjacent land use activities (primarily hunting)
on the Conaway Ranch. The Sept 1 - Feb 15 period coincides with the
hunting season. There are obvious hazards associated with public access
at the Wetlands while firearms are being used in the adjacent fields.
Conaway Ranch agreed that no hunting would take place on Mondays or the
first Saturday of the month from 3-5pm.

We are currently planning on re-visiting our access agreement with
Conaway Ranch. We will be discussing the Monday only restriction and
hope to add at least one additional weekly access day during the winter,
ideally on a weekend.

To address your second question, it is important to note that many of
the roads within the Wetlands are narrow and winding. The auto tour
route has been improved for heavy traffic use including use by larger
vehicles such as buses. The "authorized personal only" signs are there
to help keep visitors vehicles off of these smaller roads. With that
said, we do encourage visitors to park in the designated parking areas
and walk around. Foot traffic is permitted on the "restricted" access
roads. We will be updating the signs to be clear about this issue.

A final note on the limited access to the southern portion of the
Wetlands. Being as the Wetlands serve hundreds of thousands of migrating
waterfowl and shorebirds, it is important to offer some quite and
undisturbed areas for these species to forage and rest. Promoting
increased human disturbance in these areas would be a less than ideal
management strategy.

Thanks for your interest in the Wetlands and its inhabitants. Please
feel free to contact me if you have more questions or suggestions.

Sincerely,

John


-->-->-->-->-->--><--<--<--<--<--<--
John T. McNerney
Wildlife Resource Specialist
City of Davis, Public Works
23 Russell Blvd.
Davis, CA 95616
530-757-5680 Fax- 758-0354

I guess this is understandable from the Conaway and the Davis point of view but it would seem to me given the size of Conaway Ranch that the hunters could stay away from the portions that border the Davis Wetlands without too much trouble. But maybe that is where the best hunting is --- I do not know. Nevertheless, I am hoping that Davis changes its mind and tries to open up more access in the Winter. As of last week it seems no more access has been granted:

I am writing to find out if anything has been changed in terms of the winter access to the Wetlands.

I know the Winter is almost over, but I am still interested in expanding access during these months.

Jonathan

Hi Jonathan,

I have nothing new to report. We are still waiting on Conaway to commit
to a meeting time.

I'll be sure to update you if/when things change.

Thanks for your continued interest,

John

-->-->-->-->-->--><--<--<--<--<--<--
John T. McNerney
Wildlife Resource Specialist
City of Davis, Public Works
23 Russell Blvd.
Davis, CA 95616
530-757-5680 Fax- 758-0354

Is it OK to have a young earth creationist get a PhD in Paleontology?

Very interesting article in the NY Times about a Young Earth creationist who just got his PhD in Paleontology at the University of Rhode Island. The main question of the article was - should biologists consider this a bad thing? That is, if someone plans to do the work of a PhD thesis and will do it well, should their motivation for doing the PhD be considered when (1) accepting them into the program and (2) giving them the PhD?

The person, Marcus Ross is now teaching at Liberty University and some are concerned is using his credentials as a PhD Paleontologist to promote Intelligent Design as a scientific theory.

I am pretty torn about this one. On the one hand, when there ar elimited resources for training and funding PhD students, why waste money on someone who will end up probably not contributing to the field in a useful manner? On the other hand, if he is able to separate his personal religious beliefs from his scientific work, all the power to him.

I guess I have no real objection per se to him being a Young Earth Creationsist and getitng the PhD - after all many many many scientists have conflicting beliefs about science and religion. But I would object to training him if I knew that he simply planned to use his credentials to make anti scientific statements. Similarly, if someone was in the Med School at Davis and I knew they were planning on using their MD to write prescriptions for themselves and their friends, I would not support their place in the Med School. In the end, intent is a part of education and training and simply doing the work required is not enough to have me spend time helping train someone.
You can read comments on the article at the Times Website here

Guardian on Open Access

An interesting and somewhat strange article in the Guardian. In it, Ben Goldacre, who writes the Badscience column discusses Open Access to scinetific papers. He says, correctly in my mind

There are some things which are so self-evidently right and good that it’s hard to imagine how anyone could disagree with you. The “open access” academic journal movement is one of those things. It’s a no-brainer. Academic literature should be freely available: developing countries need access; part time tinkering thinkers like you deserve full access; journalists and the public can benefit; and most importantly of all, you’ve already paid for much of this stuff with your taxes, they are important new ideas from humanity, and morally, you are entitled to them.

I completely agree with this sentiment and it sums up many of the reasons I support Open Access. He also points out that

These closed journals are hardly the kind of people whose pockets you would want to line. Reed-Elsevier ..... are the same company that runs the DSEI international arms fair in London, at which vile weapons are sold to murderous regimes for cash profit extracted from very real suffering and pain, in countries you will never visit on holiday.

Finally he discussed the Eric Denzenhall hiring issue:

These people do not deserve our charity, and I will be very pleased to see you outside DSEI later this year, 300th copper from the left: because when you are so wrong you need police, security, wire fences, and the pitbull of PR to defend you, then you know you're in trouble.

I like the tone here but one thing I did not get in his article is the claim that Open Access journals cannot

get journalists to directly link to their studies. I suspect newspapers like to fantasise that they are mediators between specialist tricky knowledge and the wider public, but I wouldn't be so flattering.

I have not seen this --- I have had multiple stories written about my Open Access work and many have directly linked to my papers .... anyone have any idea what he is talking about here?

Trip to Sacramento Zoo got interesting with man's head getting stuck in photo booth

Well, went to the SacZoo with my daughter on Tuesday. Not the best zoo in the world, but it is a perfect size for her right now. She loves the Koi Pond in particular (but also the big cats and the flamingoes). The strangest part of this last visit was the guy who got his head stuck in the wooden animal cutout that you can have your picture taken in (you know, you stick your head through and take a picture from the other side).

Flock of Dodos - Evolution vs. Intelligent Design

Well, Randy Olson has done it again. Flock of Dodos is his new film. It is about the Intelligent Design vs. Evolution Debate and from what I can gather it skewers both sides of this issue quite a bit.

Randy was the head of Prairie Starfish Productions, which made some of the dorkier and funnier science moves I have ever seen including one about Loster Fisherman in New England. I first met Randy while on a Deep Sea cruise in the Gulf of Mexico where he was filming my then advisor Colleen Cavanaugh for a film about women scientists. He and I played some mischief on her associated with her first deep sea Alvin dive where we made a video of her stuffed panda being tortured.



But that is beside the point, Randy is really good about seeing through some of the facade of seriousness in science to get to the absurdities and dorkiness of some aspects of science.

So I suggest people try and check out his new film which is being screened around the country on Darwin's birthday next week.

Harold Varmus goes truly Open

Harold Varmus, one of the CoFounders of the Public Library of Science, has been featured on a NIH Profiles site. Through this site they are making a collection of his papers freely available. In addition, to co-founding PLOS, Varmus won one of those Nobel Prize thingies and was head of a little place called NIH.

Not that much is featured on the front pages. But if you go to the search page here you can search for all sorts of interesting stuff.

Some interesting ones I found:

• Letter from Us Information Agency relating to giving a talk in China after Nobel Prize.
• Notes on naming the AIDS virus
• Letter from Charlie Yanofsky (one of my favorite people in all of science) to a previous director of NIH regarding recombinant DNA
• Interesting letter to Luria about moving to MIT
  

I will post more when I have a chance but if anyone else sees interesting ones out there please post them too.

Evolution in action - Dog Breed Hybrids in NY Times

Excellent article in the NY Times Magazine this weekend on hybrids of purebred dogs.

It is basically a lesson in microevolution, inbreeding, and modern genetics. Some great lines are found throughout including

Havens moved on, like some strange Noah touring his ark — in which every tidy two-by-two had been split apart, jumbled and recombined into a single animal: “That’s a Chihuahua-bichon . . . here’s a half-American Eskimo and half-Lhasa apso” — his voice lifting each time as if to ask, What will they think of next? But he had dreamed up a lot of these things himself.

AND

Dogs with separation anxiety are now commonly treated with psycho-pharmaceuticals. Maybe re-engineering the dog itself, hybridizing newer models, represents “the last piece of the puzzle,” Bob Vetere says. “Will they reach a level of convenience where you have a postage-stamp-size dog that makes you dinner when you come home and reads the paper to you before you go to bed? I’m not sure that’s going to happen. But certainly someone’s going to try it.” After all, the dog, which we’ve molded into one of the most physically diverse mammalian species on earth, has so far been uncommonly obliging to our needs. Why shouldn’t we be capable of driving the entire species toward its inevitable end, down a millennia-long trajectory from wolf to stuffed animal?

The blade runner future is nearly with us ... what is to stop more and more twisted projects from happening? Nothing really. I mean, dog breeds are already freakish. With a little extra push, they will just get more bizarre. The really bad part of this is that the breed dogs and then kill the puppies that don't cut it for whatever their goals were. That has been happening for ages but it still saddens me.

Despite some depressing aspects of the article, it is a good read.

3rd International Metagenomics Meeting

Just got this by email ---

Dear colleagues,

We are pleased to announce that the Annual International Metagenomics Conference (Metagenomics 2007 ) will be held July 11-13, 2007, at Atkinson Hall (Calit2) at the University of California, San Diego, California (U.S.) The meeting will kick off with a networking reception and keynote presentation the evening of the 11th (Wed), followed by a full-day meeting on the 12th (Thurs) and a half-day meeting in the morning and a half-day tutorial/demonstration in the afternoon on the 13th (Fri). This is the second meeting in San Diego and the third international metagenomics conference since Metagenomics 2003, which was organized by Dr. Christa Schleper in Germany. We will update information on the meeting via this mailing list. For more information, please visit the conference website at www.calit2.net/metagenomics2007 .

Best wishes,
Kayo

--
Kayo Arima, PhD.
University of California, San Diego
California Institute for Telecommunication and Information Technology
9500 Gilman Dr. La Jolla, CA 92093-0440
Office: 858-822-4649
Fax: 858-822-5033

Science World Coming ...

The US Department of Energy and the British Library announced an agreement to develop a new international science portal aimed at sharing scientific information. It sounds like a great thing. Now if only DOE would require Open Access publishing of scientific research that they fund ... that would really show DOE's committment to Open Science. I recommend sending Dr Raymond Orbach, who is leading this initiative, an email message, the address for which you can find at this link at the top of the page.

Synthetic Biology (faculty job available at U. C. Davis in the Genome Center)

Just heard another talk by Drew Endy about Synthetic Biology and his attempts to make the field work more like Engineering than Biology. Basically, what he is trying to do is to make biological parts (e.g., Biobricks) at the DNA level that would work like circuitry board parts do for making computer chips and related devices. As they get more biological parts, more people will be able to treat synthetic biology in an abstract way - that is they will not need to know per se how the biological parts work, just that they have particular properties.

My favorite part of the field of Synthetic Biology is IGEM, the The international Genetically Engineered Machine competition. Students compete to make cools things from their biological parts. Among the more interesting items that have been made is a bacterallawnthat work as a camera.

In general, I like synthetic biology and the potential it has to produce major benefits for the world, although I wish some of the practitioners were less flippant about the potential risks in the field. And, this minor blog would not be complete without the self interest. THe UC Davis Genome Center has just announced a new faculty position in this area (specifically in cmputational and experimental approaches to network and synthetic biology). So if you are in this field and want to join a great collection of faculty working in diverse areas of genomics, please apply.

Job at Davis

Non Open Access publishers getting desperate

Well, this kind of made my day. Nature is reporting that a group of non open access publishers have hired Eric Dezenhall to help them with public relations. Eric Dezenhall is a crisis management consultant (as well as a fiction author) who many may demonize but he certainly seems to be good at what he does. The article at Nature is worth checking out and points to the desperation of these publishers when they see the writing on the wall regarding Open Access. For example, Nature reports a person at AAP the Association of American Publishers says:

"We're like any firm under siege," says Barbara Meredith, a vice-president at the organization. "It's common to hire a PR firm when you're under siege."

Keep up the siege everyone. Their ship is sinking and they are grabbing at the last little pieces of wood they can find.

Article in the Christian Science Monitor on PLoS One and related topics

Just saw an interesting article in the Christian Science Monitor on the "end of the scholarly journal" which talks quite a bit about PLoS One. Definitely worth checking out -- many quotes from Chris Surridge of PLoS One and some discussion of Blogs and related sites.

Antibiotic resistant bacteria plaguing US soldiers in Iraq

Very interesting article in Wired magazine about an antibiotic resistant bacteria that is plaguing US soldiers in military hospitals in Iraq. It's got some stuff I would disagree with in there about gene transfer and evolution but overall this is a really good and interesting article about bacterial evolution and antibiotic resistance.

Interesting (but misguided) letter to the editor

There is a funny/interesting letter to the editor in one of the local papers out here. It is basically about how an article on Neanderthals is interesting but how more should be written about current topics in evolution, which sounds great. Then the author proceeds to quote Fisher and Morgan regarding human evolution, not the most modern of research to quote. Anyway, the calculation they made I found to be quite interesting ...

Blog apologies --- evolution happens

Well, sorry for the limited number of postings here recently. I am working on increasing my own fitness --- we have a baby due next week and my blog has fallen a little behind. I will get back into blogging more in about 3 weeks. If I see anything interesting before then I will post but there may still be a short lull. Now back to getting 1,000,000 things done in one week.

Genomics Gets Nasty

Just saw an entertaining press release about the publication of the genome of the parasite Trichomonas vaginalis. I find this entertaining because it does a remarkable job of capturing the personality of Jane Carlton, the PI on the project, who I used to work with at TIGR.

I particularly like the end

Viewed under the microscope Trichomonas vaginalis moves quickly; it has four undulating flagella and a tail. "It is a gassy organism," says Dr. Carlton. It has special power-generating structures called hydrogenosomes. They produce hydrogen. "So it is releasing hydrogen into the liquid media, making it frothy," she says. "That is why the vaginal discharge is frothy."

The pathogen grows easily in the lab in test tubes containing some liquid media. And it has, as she says, "a real yuck factor to it." A good way to know the microbe is growing well is to smell the contents of the test tube. "It smells foul, it has a fishy odor; really nasty," says Dr. Carlton. "My technician used to get grossed out by that."

While it is true that Jane has no fear about saying things that make some people uncomfortable, it is entertaining to the it in the NYU press release.

The press release is worth reading for another reason - the history of this genome project is different from many other parasites. In this case, the genome was enormously bigger than had been predicted (usually they are smaller than predicted, in part becuase if you over predict the genome size, you will have some extra money in your grant to cover other issues). The press release gives a good impression of how much of a pain it is to run a genome project sometimes.

Anyway - back from a little layoff and just wanted to say - good job Jane.

Open Access Education?

Thanks to Jacques Ravel for pointing this out. U. C. Berkeley has begun posting many of its science classes as Podcasts which are avilable for download at a special Apple Itunes Site. Also posted are some lectures such as one by George Smoot who just won one of those Nobel Prize thingies. It seems Stanford is doing a similar thing although it does not seem as extensive.

Note sure what other Universities are doing this (I know some classes are podcasting but not clear how many Universities are doing it as extensively as Berkeley).

If anyone else knows of other such efforts please let me know (also see this list of free academic podcasts).

My Open Access New Years Resolutions

Well, 2006 is over and in terms of Open Access to Biomedical type publications, I think it was a pretty good year. The papers being published in Open Access journals continue to get better and better and there are more Open Access journals too. Perhaps to biggest new thing from last year was the start of PLoS One, which is not only an Open Access journal but one that is experimenting with a new type of peer review system.

But of course, more needs to be done. So I am posting here my personal list of Open Access New Years resolutions. These are things I hope to do and hope to convince others to do too (these are in no particular order).

1. Convince more collaborators to publish papers in Open Access journals.

2. Release more of my labs data in a more usable format to Open Data archives (see Bill Hooker's Open Reading Frame blog for more details about doing this).

3. Discuss Open Access to publications and data in all my scientific presentations/talks.

4. Write more blogs about Open Access and its benefits.

5. Convince some existing journals to switch to a more Open Access stance (e.g., I wish this would happen with Journal of Molecular Evolution --- I resigned my position as an Academic Editor when they would not shift but there is still hope).

6. Submit as many of my past papers that were not in Open Access journals to self-archiving repositories (see the comments on my previous blog about this - it seems that this is possible even for Nature papers).

7. Work with Pubmed Central to make self archiving possible there for more papers. Right now it is only possible to submit your own work to Pubmed Central if it was NIH or Wellcome Trust funded.

8. Discuss Open Access with more scientists. Some still have notheard about it and some do not realize what the issues are.

9. Discuss Open Access with more non scientists. To get Congress to pass more rules regarding Open Access, it will help to have more pressure from non scientists. When I have described the current publishing system to non scientists, they are usually astonished by the (1) wasted money and (2) closed nature of much scientific work.

10. Work to get researchers who publish in Open Access journals "extra credit" in promotions, tenure review and grant proposal review. These people are frequently taking risks for the betterment of the scientific community and to advance scientific knowledge. They deserve credit for taking these risks.