Flu Evolution Revisited and Biology Direct's Foray into Open Peer Review

Anyone interested in scientific publishing and/or the flu should check out a new paper in the journal Biology Direct. The paper suggests a new way of thinking about flu evolution. Whether you agree with the authors or not (I am still not sure), what is most interesting about this to me is that the reviews are posted online as are the authors responses. See the paper here and some stories about it here and here.

Biology Direct is an Open Access journal that is experimenting with the peer review system. Their experiment is quite intriguing in its methods. For details see here and here.
Basically, the author is charged with selecting reviewers and then getting the reviews. Then the paper can be published along with the reviews, whether they were positive or negative. The author can make changes based on the reviews or can choose not to. Thus someone could publish complete crap, but since the reviewers will be named publically, hopefully the reviews will indicatethat it is crap. The key to this is that the author has to select people from the Editorial Board that then select the reviewers. So as long as the Editorial Board is reasonable, the review process should be OK (note - I am on the Editorial Board although I have not been asked to do anything yet).

Do I like this system? I am not 100% sure. But I admire Eugene Koonin and colleagues for trying something different and giving the world an example of a possible way to get around the flaws of the current review system. Of course, to me, the most important thing is that the journal is Open Access, which means that anyone out there can get a fascinating look at peer review for free.

For example, people should really check out the paper and the reviewers comments and the authors responses. Or even better check out some other papers in the journal. It makes for a good read.

Evolution and Politics

Scientists are acting up again. The New York Times reports that

75 science professors at Case Western Reserve University in Cleveland have signed a letter endorsing a candidate for the Ohio Board of Education.

This is great news if you ask me. Scientists seemed to be emboldened to play more of a role in politics. I think this is due to some of the recent pushes from anti-science coalitions, like the supporters of "intelligent design" as a scientific theory (which it is clearly not).

We desperately need more of this type of thing - with scientists speaking up. I do not want scientists to choose sides in truly political debates. And I hope scientists will avoid being too arrogant - such as when some suggest science can solve all the worlds woes. But when sound science is being ignored or belittled by politicians, scientists should speak up. The evolution debate is but one example. There are many more issues where sound science is being misused or ignored (e.g., global warming).

So - I recommend all scientists consider doing something to get involved. Lend your support to the folks in Ohio (e.g., Lawrence Krauss organized the group to write the letter). Or join an organization like SEFORA a new science based political action group. But just don't sit on the side and say "scientists should not get involved." If all scientists keep doing that, we are in deep trouble.

The latest genomics buzz

The latest buzz in genomics is about the honeybee genome. The people working on this genome have really done a good job of organizing themselves (a sort of model social genomics network in a way). They have a veritable slew of papers coming out this week on various things about the genome and about honeybees that were learned by making use of the genome.

There is an entire issue of Genome Research dedicated to studies of the honeybee (see the press release here) including papers on rates of evolution, circadian rhythms, chemical sensing, sex and death (of course), and even the royal jelly. If you don't know what royal jelly is, do a google search for that. There is also an overview article in Nature and a genome report in Science. In total 170 researchers were involved in these papers.

Mind you, I am disappointed that these were not published in Open Access journals. And this is particularly sad given that the funding came from the NHGRI, the same group of sanctimonious individuals who kept talking about how the "public" human genome project was "open" in every way for the betterment of humanity. Unfortunately, what they mean by "open" even for the human genome project is a bit of a misnomer. They meant that people could look at the data immediately. But they restricted how people could use the data, despite their attempts to pretend otherwise. Consistent with this, the groups funded by the NHGRI generally do not publish their papers in Open Access journals. Shame shame shame.

OK, enough sniping. The honeybee is so fascinating biologically in so many ways that this genome sequence deserves a bit of extra attention. First, honeybees are social creatures. They have in fact been one of the key models in studying both the evolution of social behavior but also communication among organisms.

Another aspect of their biology that is very interesting is their genetic structure. Like other hymenoptera they have what is know as a haplodiploid life cycle with males being haploid (the result of unertilized eggs) and the females being diploid. This unusual genetics is another reason that honeybees and other hymenoptera have been studied extensively by biologists for many years. In fact, a great little bit of history about this is in a book on the history of studies of altruism from Princeton University press. One of Darwin's biggest concerns in the origin of life related to the self sacrifical behavior, especially that in honeybee colonies. Apparently, honeybees were a topic of conversation among non scientists and the non reproductive worker castes were well known to the public. Darwin struggled quite a bit to come up with a good explanation that was consistent with natural selection for why some individuals would sacrifice their lives for others.

Dawrin actually cam up with a good logical explanation for this - that some individuals would sacrifice if they were related to others who would benefit. Bees and their relatives played a large part in studies that have revealed in much greater detail how altruism can evolve. They may not be as warm and fizzy as some other organisms being sequenced, but they certainly were a good pick for a genome sequencing project.

Science Lobbying - The role of science in politics and vice versa - Scientists and Engineers for America

I listened to a very interesting Science Friday Podcast today (I listen to them on my bike rides to/from work here in Davis, CA, the most bike friendly town in which I have ever lived). This particular podcast had as one of the guests Susan F. Wood. Some people may remember that she resigned from a top job at the FDA over what she felt was politics getting in the way of good science.

Well, rather than disappear as some higher ups in the executive branch do after quitting, she has jumped into a whole new realm. She has helped start a group called Scientists and Engineers for America. Their aim is to help elect to office people

who respect evidence and understand the importance of using scientific and engineering advice in making public policy

from the NY Times article about this.

They have even created a "bill of rights" for scientists. Among the rights they include:

Federal policy shall be made using the best available science and analysis both from within the government and from the rest of society.

The federal government shall never intentionally publish false or misleading scientific information nor post such material on federal websites.

Scientists conducting research or analysis with federal funding shall be free to discuss and publish the results of unclassified research after a reasonable period of review without fear of intimidation or adverse personnel action.

Federal employees reporting what they believe to be manipulation of federal research and analysis for political or ideological reasons should be free to bring this information to the attention of the public and shall be protected from intimidation, retribution or adverse personnel action by effective enforcement of Whistle Blower laws.

No scientists should fear reprisals or intimidation because of the results of their research.

Appointments to federal scientific advisory committees shall be based on the candidate’s scientific qualifications, not political affiliation or ideology.

The federal government shall not support any science education program that includes instruction in concepts that are derived from ideology and not science.

While scientists may elect to withhold methods or studies that might be misused there shall be no federal prohibition on publication of basic research results. Decisions made about blocking the release of information about specific applied research and technologies for reasons of national security shall be the result of a transparent process. Classification decisions shall be made by trained professionals using a clear set of published criteria and there shall be a clear process for challenging decisions and a process for remedying mistakes and abuses of the classification system.

I confess to being a little worried that they may become too partisan and to be effective I think they should try to be as non partisan as possible (although there is no doubt that the current administration has violated more of the items in their bill of rights than probably any previous administration). Neverthless, this sounds like a great idea and hopefully they can help increase the use of science in decision making.

To sign up go to http://www.sefora.org/

Genomics Education Bus

I just got back from the new version of the old GSAC meeting. It is now called GME or Genomes, Medicine and the Environment (or, as we like to call it - stuff Craig Venter is interested in these days). The meeting is organized by the Venter Institute and this year was one of the better versions of this meeting. There were some really interesting talks in a few topic areas (I will try and post some details about these later). But to me, the most interesting part was seeing the Venter genomics education bus (part of their Genomics Discovery program) on tour. They use this bus to go around to high schools and other places to do some genomics education.

Just before coming to the meeting, the bus apparently rolled into New Orleans (see Wired news story here). Lots of people like to complain about Venter and his style, but whatever you may think of him, I think this bus is a great idea. We desperately need more people who do science making an effort to interact with and educate people about scientific research. And since this bus is outfitten with lab equipment and various genome-related toys, it can go into a neighborhood without the best science labs and help introduce students to the fun and excitement of modern science.

Note - the photo was taken by me at the GME meeting in Hilton Head, SC. In the photo are Lisa McDonald, Jennifer Colvin, and (I think) Darryl Bronson.

Harvard Crimson changes its mind - supports PLoS One

Well, the folks at the Harvard Crimson have apparently changed their mind. In a new Editorial, two writers from the Crimson discuss PLoS One and open peer review. Unlike the previous Crimson editorial (see my blogs about it here and here), the two writers of this one now come out clearly in support of the PLoS One idea as well as some PLoS ideals.

For example, the liken the battle between Open Access and Closed Access publishing to the battle over democracy

Democracy has reached a new frontier, and we’re not talking about the Berlin Wall. It’s a new decade and a new millennium, and yet another wall is crumbling—this time, not between countries, but in the domain of scientific research.

Perhaps most importantly, they end the editorial with

Initiatives such as PLoS ONE will help promote free and unfettered scientific study, supplementing and revolutionizing an oligarchic academic process. It is both ignorant and regressive to reject this democratization.

Although they did not address the previous highly ignorant editorial in their own newspaper, Yifei Chen and Patrick Jean Baptiste deserve kudos for a well written, well thought out editorial on a key topic for the whole endeavor of science.

World's Smallest Genome of a Cellular Organism?

A one page paper in Science reports on what I think is one of the most exciting findings in microbial genomics in years. The reports describes the sequencing and analysis of the genome of a bacterial endosymbiont of an aphid. This bacteria, known as Carsonella, has a TINY genome - only 160 kbp in length. This is ~ 3 fold smaller than the previously known smallest genome - that of Nanoarchaeum equitans which has a genome of 490 kbp.

I think almost certainly this symbiont should be considered an organelle. It is missing many cellular functions found even in the most reduced symbionts. Thus in essence it may not be the smallest genome of a cellular organism. But who cares how we define it. If it is a new organelle - that is amazing. If it is a tiny cellular genome - that is amazing too.

One thing that strikes me as strange is the fact that the paper is only one page long. It contains so little detail on what was done and what was found in the genome that the story is woefully incomplete. This I would guess is somehow related to a rush to publish but also likely due to it being published in Science, which has severe page restrictions.

This paper has been getting ENORMOUS press coverage for valid reasons. But I agree with Craig Venter (see the New Scientist article) that this genome is not of much relevance to efforts to create a "minimal" genome. This is because the ideal minimal genome is one that can support independent life. Carsonella, is far from independent and thus represents a really wild evolutionary story, but nothing of much relevance to minimal genome studies.

Some related links:

• Commentary by Siv Andersson
• NPR Story
• Nancy Moran's Home Page (one of the corresponding authors of the paper)
• World Science article

Nakabachi, A., Yamashita, A., Toh, H., Ishikawa, H., Dunbar, H., Moran, N., & Hattori, M. (2006). The 160-Kilobase Genome of the Bacterial Endosymbiont Carsonella Science, 314 (5797), 267-267 DOI: 10.1126/science.1134196

Harvard Crimson Editorial Update

OK - so I am biased here but those interested in Open Access should check out my brother's letter to the Harvard Crimson that was published today. He wrote it in response to the lame editorial the Crimson wrote about PLoS One. Some of my favorite quotes from his letter

They did not, however, respond to your repellent effort to rally the forces of elitism to derail a project whose primary aim is to rapidly bring scientific knowledge to everyone.

....

Once they see PLoS One, we are confident that consumers of scientific papers will discover what employers have long ago: If you’re looking for the imprimatur of greatness, try Nature or Harvard—but if you want the real thing, try PLoS One or Berkeley.

Of course, I disagree with the use of Berkeley in this context. Yes it is a public school. But come one - to use Berkeley as the "anti"elitist school of the world is a big stretch. So if you want the real thing, try U. C. Davis, not Berkeley.

Open Access Biology highlights - The Intriguing Life of Endosymbionts

Two new articles published in the last issue of PLoS Biology bring forth some wildly interesting details about the lives of endosymbiotic bacteria.

One of the articles is about the role Wolbachia may play in speciation in Drosophila species. Wolbachia are a type of bacteira that are found to infect a wide diversity of invertebrate species. These bacteria are transmitted directly from mother to offspring much like mitochondria. Interestingly, many have evolved specialized means of negatively impacting male offspring. In the PLoS Biology study, the researchers were working on a type of Wolbachia known to cause cytoplasmic incompatability in which infected male offspring cannot produce offspring with uninfected females. Since these males can produce offspring with infected females, this helps contribute to the spread of the Wolbachia in the population. To make a long story short, the current paper proposes that not only can Wolbachia apparently lead to speciation through behavioral affects on the host, but that these affects can be stimulated even in species not infected by Wolbachia, if another similar species in the same area is infected. To learn more about the study read the synopsis here. I am personally interested in this story because we published the first Wolbachia genome a few years ago in PLoS Biology.

The second story to me is even more interesting. This relates to a bacterial symbiont that is found in the gut of a stinkbug species. The paper is important because the symbiont in this case does not live inside the cells of its host as do many other gut symbionts of insects. Instead, the symbiont lives in an extracellular capsule. Interestingly, the symbiont is transmitted to offspring not directly in eggs as in many other symbionts, but indirectly. The mother deposits a mass of the bacteria near the eggs and these are then consumed by the young just after hatching (the video of this is amazing).

The paper shows that these symbionts possess many of the genomic features found in other transmissable symbionts - including small genomes, high AT contents, and high rates of evolution (you can read more about this in my recent paper on symbionts of the glassy winged sharpshooter here or in my earlier blog). Many previously thought that these genomic features were related to the intracellular lifestyle of symbionts. But given that the same features are found in these extracellular symbionts, this suggests that the shared genome features are probably related to experiencing population bottlenecks in transmission from mother to offspring. See the synopsis of the paper here.

Harvard Crimson PLoS One "Commentary"

Well, the newspaper of Harvard has posted an editorial about what they call "Science in Print." The editorial is disappointingly a confusing mashup of ideas, facts, and flasehoods regarding PLoS One. The Crimson folks criticize online science journals under the idea that none of them are peer reviewed. They take issue in particular with PLoS One because they think it is to have no peer review at all. Fortunately, Chris Surridge, Pedro Betrao, and others have already posted messages to the comments section online about this correcting many of the mistakes in the editorial.

What is most disappointing to me about my undergraduate institution's newspaper's actions is that they seem to have written this editorial without even taking the time to read anything about the system they were criticizing. In doing some google searches I cannot even figure out where they got some of the misinformation they cite regarding PLoS One.

I completely understand people being uncomfortable with some aspects of the PLoS One system. Any change is scary to scientists and to supporters of science. But the experiment PLoS One is carrying out is not about replacing peer review entirely. It is about modifying the peer review system slightly (basically - papers will be reviewed for techincal quality only and not things like novelty) and also about adding a better evaluation system for scientific publications. I confess, I am not sure it is the perfect idea. But the world is a very very different place than it was when the current scientific publishing paradigm was established. We need to try some new ways of publishing if science is to take advantage of the internet driven, blogging, podcasting, mashup, [insert favorite technojargon here], world.

Metagenomics 2006

Just got back from the "First International Conference on Metagenomics" which was held in San Diego. Despite that this is clearly NOT the first international conference on metagenomics it was not bad.

For those who do not know, metagenomics is the term used when people do DNA sequencing directly from environmental samples without isolating organisms in the first place. This term was coined by Jo Handelsman et al. in an article in 1998, where they referred to all the DNA and its coding potential in soil as the soil "metagenome."

The meeting was hosted by UCSD/CalIT2 which are trying to move into the metagenomics field in a large part due to the large grant they have from the Moore foundation to build a metagenomics database with the Venter Institute. The database is called CAMERA and it is planning to have its first release shortly.

To be honest, even though I am involved in CAMERA, the UCSD/CAMERA folks would be better off not trying to make it seem like they are the only people organizing meetings in this area. Nevertheless, the meeting was pretty good.

There were talks by people focusing on different aspects of metagenomics, including data collection, databasing, and data analysis as well as some interesting biology. My favorites were one by Jeff Gordon, from Wash. University in St. Louis. He is doing some of the most spectacular stuff in studies of the human microbiome and he discussed a few of the studies from his group. Most importantly, he emphasized the use of germ free animals as a model system. Basically, they raise animals in completely sterile conditions and have produced mice and fish and other species that have no microbes associated with them. This allows them to do experimental manipulations to ask controlled questions about host microbe interactions. My other favorite talk was by Ford Doolittle, who even though I disagreed with some of the things he said, he always challenges the audience to rethink their assumptions. In this case, he talked about the species concept in microbes and why he thinks it does not have much us.

Overall, I got the feeling that people were being a little too worried about the difficulties in metagenomics. Yes, analyzing sequence data from environmental samples is complicated. Yes, all the bioinformatics is harder because you are dealing with a mixed sample of DNA fragments and you do not know which fragment comes from which organism in the sample. And yes, the databasing and data analysis can be very complicated because the amount of raw data and metadata can be huge. But in the end, metagenomics has the potential to be an incredibly powerful tool in studies of microorganisms in nature. And the fact that it is somewhat harder than standard genome sequencing does not mean that we are not already learning a lot from it. What we need to keep in mind is that it is simply a tool - and to try and turn it into a field (which is what it seemed like some of the players would like) is a mistake.

If you are interested in the meeting itself, the talks and discussion sessions are available here.