I would have put Botany in Fangorn (because of the Ents), Microbiology in the Sea of Rhûn for beyond it are “wide uncharted lands, nameless plains, and forests unexplored” and machine learning in the Misty Mountains (close enough to Bioinformatics, statistics and Computer Science).

Also, if the social sciences are in Mordor, what does that say about Sauron?

JSUR Call for Participation

Submit your short (2-4page) and full length manuscripts to the Journal
of Serendipitous and Unexpected Results.

Over the past month we’ve received a great amount of press and
publicity for the Journal of Serendipitous and Unexpected Results
(JSUR). Thanks to everyone who helped spread the word, please keep it
up!

In Richard Feynman’s 1966 Nobel Lecture, he said, “We have a habit in
writing articles published in scientific journals to make the work as
finished as possible, to cover up all the tracks, to not worry about
the blind alleys or describe how you had the wrong idea first, and so
on. So there isn’t any place to publish, in a dignified manner, what
you actually did in order to do the work.”

We’re writing to invite you to solicit short (2-4page) and full length
submissions to JSUR.  Why not prepare a 2-4 page writeup discussing
side-investigations, alleyways, or false-starts in your latest
published or unpublished research? Papers of this length place a
minimal burden on the authors, while providing extremely valuable
research insights to a broad audience.

Journal website: http://www.jsur.org

Sincerely,
The JSUR Editorial Board

The most exciting phrase to hear in science, the one that heralds new
discoveries, is not ‘Eureka!’, but ‘That’s funny…’ -Isaac Asimov

Thanks to Ruchira Datta for pointing out this one.

Science is many things to many people, but any lab-rat will tell you that research is mainly long stretches of frustration, interspersed with flashes of satisfying success. The best laid schemes of mice and men gang aft agley. A scientist’s path contains leads to blind alleys more than anything else, and meticulous experimental preparation only serves to somehow mitigate the problem, if you’re lucky. This doesn’t work, that doesn’t work either and this technique worked perfectly in Dr. X’s lab, why can’t I get this to work for me?  My experiment was invalidated by my controls; my controls didn’t work the way the controls were supposed to work in the first place. I keep getting weird results from this assay. I can’t explain my latest results in any coherent way… these statements are typical of daily life in the lab.

This stumped and stymied day-to-day life is not the impression of science we get from reading a research paper, when listening to a lecture, or when watching a science documentary show. When science is actually presented, it seems that the path to discovery was carefully laid out, planned and  flawlessly executed, a far cry from the frustrating, bumbling mess that really led to the discovery. There are three chief reasons for the disparity between how research is presented, as opposed to what really goes on. First, no one wants to look like an idiot, least of all scientists whose part of their professional trappings is strutting their smarts. Second, there are only so many pages to write a paper, one hour to present a seminar or one hour for a documentary: there is no time to present all the stuff that did not work. Third, who cares about what didn‘t work? Science is linked to progress, not to regress. OK, you had a hard time finding this out, we sympathize and thank you for blazing the trail for the rest of us. Make a note for yourself not to go into those blind alleys that held you back for years and move on. We’re not interested in your tales of woe.

Only maybe these tales of woe should be interesting to other people. If you make your negative results public, that could help others avoid the same pitfalls you had. If you share the limits of a technique, a protocol or software then someone can avoid using it in a way that does not work. A lab’s publications are actually the tip of the sum total of its accumulated knowledge.Every lab has its own oral tradition of accumulated do’s and dont’s. Not oral in the literal sense: they may even be written down for internal use, but never published. UPDATE (2-FEB-2010): most peer-reviewed journals don’t like stuff that does not work. Thanks to Mickey Kosloff for pointing out the Journal of Negative Results in Biomedicine and The Journal of Negative Results – Ecology and Evolutionary Biology.

Until now.

The Journal of Serendipitous and Unexpected Results aims to help us examine the sunken eight-ninths of the scientific knowledge iceberg, in life science and in computer science. (So an additional field over JNRB and JNREEB). From JSUR’s homepage:

Help disseminate untapped knowledge in the Computational or Life Sciences

Can you demonstrate that:

* Technique X fails on problem Y.
* Hypothesis X can’t be proven using method Y.
* Protocol X performs poorly for task Y.
* Method X has unexpected fundamental limitations.
* While investigating X, you discovered Y.
* Model X can’t capture the behavior of phenomenon Y.
* Failure X is explained by Y.
* Assumption X doesn’t hold in domain Y.
* Event X shouldn’t happen, but it does.

The problem with the JSUR model, and the nature of discovery

I expect JSUR will be a great way to comment on  methods and techniques. Indeed it will codify a trend that has been going on for some time: public protocol knowledge sharing. Many sites like openwetware,  seqanswers or the UC Davis bioinformatics wiki have been doing this for a while. Not to mention a plethora of blogs. Scientists are willing to share their experience with working protocols and procedures, and if this sharing of knowledge can be now monetized to that all-important coin of academia, the  peer-reviewed publication, all the better.

So where is the problem? The problem lies with discovery, and credit given towards it. It would be very hard to get anyone to share awkward, unexpected or yet-uninterpreted results. First, as I said, no one wants to look like an idiot. Second, unexpected or yet uninterpreted results are often viewed as a precursor to yet another avenue of exploration. A scientist would rather pursue that avenue, with the hope of  the actual meaningful discovery occurring in the lab. At most, there will be a consultation with a handful of trusted colleagues in a closed forum. If the results are made public, someone else might take the published unexpected and uninterpreted results, interpret them using complementary knowledge gained in their lab, and publish them as a bona-fide research paper. The scientist who catalyzed the research paper with his JSUR publication receives, at best, secondary credit. The story of Rosalind Franklin’s under-appreciated contribution to the discovery of the structure of DNA comes to mind. Watson and Crick used the X-ray diffraction patterns generated by Franklin to solve the three dimensional structure of the DNA molecule. Yet she was not given a co-authorship on the paper. (And she did not even make the results public, they were shared without her knowledge.) Unexpected results are viewed either as an opportunity or an embarrassment, and given the competitive nature of science, no on wants to advertise either: the first due to the fear of getting scooped, the second for fear of soiling a reputation. I expect JSUR would have a harder time filling in the odd-results niche, but I hope I am wrong.

But if you have protocols you are willing to share…what are you waiting for? Get those old lab notebooks, 00README files, forum posts  and start editing them to a paper. You are sitting on a goldmine of publishable data and you did not even realize it.

Finally, here are two scientists who never declined sharing their unexpected results.

This post has been slashdotted. Exercise extreme caution.

Muahahaha!

Today is the 366th birthday of Sir Isaac Newton. Formulator of the three laws of motion, the theory of gravity, inventor of the first reflecting telescope, theory of color, calculus (with due credit to Gottfried Leibniz), the generalized binomial theorem, and president of the Royal Society.

Newton in a 1702 portrait by Godfrey Kneller

All which ties in directly to retail, and biodiversity. Huh?

Co-operative Farms (UK) recently bought 1,000  rare and endangered apple varieties, with colorful names like Great Expectations, Fairie Queen, Northern Spy, Forty Shilling, Duck’s Bill and Bloody Ploughman. (I wonder how the last name came to be; actually, maybe I shouldn’t.) This also includes Isaac’s Newton’s Tree: the apple variety cultivated from the descendants of the tree which inspired Newton to formulate the Theory of Gravity. Many of those apples were dessert apples, but some fell out of favor the strains were no longer grown, threatening to disappear.

Co-op Farms are bottling them up as the “Truly Irresistible Tillington 1,000″ pressed apple juice. I think it is great that a retail chain is funding crop diversity and finding a way to make some money in the process. Although with 7,500 cultivars worldwide, apples as are not exactly under an extinction threat. But there is also the matter of food variety, cultural heritage and, of course, preserving the history of physics. Or bottling it up, whichever the case may be.

Also, fruit, including apples, are important in the small-arms industry:

Here’s a really cool work, published this September in Nature.. Why did I choose this work?  Well, it’s a major discovery, and it’s all done using bioinformatics, and fairly simple bioinformatics at that. The power of metagenomics and bioinfromatics: in a mass of data you just have to know what you are looking for, and how to look for it.

Obviously not CC licensed, but I couldn't resist using this very appropriate strip

Viruses as a bacterial genetic mechanism

Viruses follow some interesting and sometimes convoluted evolutionary paths.  One is “infect quick, reproduce fast, and make sure you can get to the next host before you kill this one”.  That is pretty extreme: smallpox was doing that, when there was smallpox. Ebola is doing that, but not very well: killing the host too quickly means that the disease is contained, especially in rural areas. Another strategy is: “slow and easy wins the race”. The herpes virus does that. Not lethal, but laying dormant in the central nervous system, it is  infectious, but rarely causes anything more than they occasional cold sore (which admittedly, is painful and disturbing). Still, it manages to infect up to 90% of the human population, most of which are completely unaware they harbor it, and would never develop any symptoms.

Most of the viruses on earth don’t infect humans, nor animals, nor plants. They infect microbes, where the same spectrum of evolutionary strategies applies. Some attack quickly, killing the microbial population they infect. Other can remain dormant for a long time. It is becoming clear to us that bacterial viruses or bacteriophages, are responsible for a large portion, if not the majority, of genetic variance in bacteria. In fact, viruses are a major component in bacterial genetics. The mechanism is called transduction, and it is illustrated below. Bacteriophages pick up DNA from bacteria they infect, and transfer it to other bacteria, creating genetic variance in the bacterial population.

Generalized transduction. Source: Indian River State College

Viral transduction also adapts

But viral transduction does not just carry random genes. Natural selection favors transduced genes that increase the bacterial host’s fitness. Because when a bacteria is infected by a virus, its protein making machinery is used to make viral genes. But when the viral genes include genes that are beneficial to the host as well, then everybody wins: the phage-infected bacterial species gets genes which enable it to compete better for resources with other bacterial species, while the phage gets a larger number of hosts to infect. Of course, this has to go hand in hand with a relatively benign virus that remains dormant long enough to let the bacterial host species enjoy the benefits of the transduced genes.

Such is the case of cyanophages and cyanobacteria. Cyanobacteria are photosynthetic bacteria, and cyanophages are the viruses that infect them. Several studies have shown that cyanophages have acquired whole photosynthetic genes from bacteria. Viruses do not photosynthesize, but when they infect cyanobaceria, the viral photosynthetic system is added to the bacterial one, boosting bacterial photosynthetic activity and ultimately increasing bacterial energy production.

The photosynthetic mechanism is  divided into two components: photosystem I and photosystem II (PSI and PSII). For a few years now, PSII has been known to be transduced by cyanophages.

A  more recent study by Itai Sharon and colleagues published in Nature this September shows that PSI proteins are also tranduced by cyanophages. Also, it seems like the viral PSI has some interesting properties that may make it advantageous over the cyanobacterial PSI. Two proteins in the bacterial PSI are called PsaJ and PsaF.  They found that the homologous protein in cyanophages is a fusion of the two, PsaJF. When they modeled an insert of PsaJF into the bacterial photosystem I it seemed that the bacterial PSI with the viral insert can now function more efficiently than the the original bacterial PSI. As a rule, PSI is a system that accepts electrons from PSII via a protein called plastocyanin. The donated electrons are excited by light, and the energized electrons are used to synthesize ATP and NADPH, the energy coinage of the cell, which are used to synthesize sugar from CO2. However, when the bacterial PsaJ and PsaF are replaced by the viral compound PsaJF, it seems like plastocyanin does not have to be the only electron donor to the newly minted virally-donated PSI. This means that the PSI may now accept electrons not only from plastocyanin, but from other electron-carrying proteins as well. Such proteins that are involved in the respiratory system, for example, which also donate electrons. The advantage of such a setup is that electrons whose reducing power would otherwise go to waste, got through PSII for formation of extra NADPH and ATP. Sharon and colleagues do not prove all this experimentally, but they make a pretty strong case, citing some analogous cases.

Electron transport from PSII to PSI via plastocyanin. Source: wikimedia commons.

a, The structure of T. elongatus PSI (subunits) was illustrated by PyMOL (http://pymol.sourceforge.net/) using a PSI monomer (adopted from Protein Data Bank (PDB) accession 1jb0). PsaF is in magenta, PsaJ is in blue, and all of the other subunits are in green. b, A model for the structure of the viral PsaJF fusion protein (red) substituting the original PsaF and PsaJ subunits. Reproduced under NPG Licensing terms for non-commercial / educational purposes. doi:10.1038/nature08284

Like I said,  this work is purely bioinformatics. They basically mined the Global Ocean Survey metagenomic data, over six million sequences from marine microbes collected by the J. Craig Venter Institute which I mentioned in another post. They then identified sequences that contain PSI genes, and sifted through those to find sequences that also contain genes that are exclusively viral. Having both a PSI gene and a viral gene on the same DNA clone ensures they were taken from a virus. I’m not sure how they did the structural modeling and insertion of the PsaJF. This seems to be missing both from the Nature article, and the supplementary material. Yes, it’s one of those Nature works with 3 pages of article, and 28 of supplementary. Great read though, there’s treasure everywhere.

Lindell, D., Jaffe, J., Johnson, Z., Church, G., & Chisholm, S. (2005). Photosynthesis genes in marine viruses yield proteins during host infection Nature, 438 (7064), 86-89 DOI: 10.1038/nature04111

Dear friends and colleagues:

It’s now been over a week since Warren has passed away.  We are trying to
move toward a permanent way to honor Warren’s memory and what
he stood for: Open Source Computational Biosciences and molecular
visualization. To do this, Jim Wells and I put together a mission statement
with the approval of Warren’s family:
The Warren L. DeLano Memorial Award for Computational Biosciences

This award shall be given to a top computational bioscientist in
recognition of the contributions made by Warren L. DeLano to creating powerful
visualization tools for three dimensional structures and making them freely accessible.
The award, accompanying lecture, and honorium will be given annually in the context of a
national bioscience meeting or a Bay Area gathering of
computational bioscientists at Stanford, UCSF or UC Berkeley. For the award special emphasis
will be given for Open Source developments and service to the bioscience community.
The award selection committee, consisting of experts in the computational and
biological sciences, will accept nominations from anyone.
To make something like this happen in perpetuity would take about ~100K for
the endowment.

For donations, Warren’s family has set up a tax deductible fund:

Silicon Valley Community Foundation
memo:  Warren L. DeLano Memorial Fund
2440 West El Camino Real, Suite 300
Mountain View, CA 94040
tel: 650.450.5400

We hope that you’ll consider making a contribution (not matter
how small) in Warren’s honor.  Also, please forward this message
to anybody who might be able be willing to contribute.

Best regards,
Axel

Axel T. Brunger
Investigator,  Howard Hughes Medical Institute
Professor of Molecular and Cellular Physiology
Stanford University

First, a victory dance:

Next, the scientific background:

And part of Ada Yonath’s model in this clip:

Credit: wikimedia commons

Prestige and controversy go hand in hand, mix in science and you have a concoction more explosive than the one Mr. Nobel himself invented. Who won, who didn’t win  and which achievement was never recognized.  This week’s BsB’s poll asks: which category would you add to the Nobel prize? Feel free to mark “other” and add your own in the comments.

Credit: wikimedia commons

By the way, Alfred Nobel’s wife did not sleep with a mathematician. That is not the reason why there is no Nobel prize in math. Get real.

Also, it might be a good idea to remember the spirit in which Nobel wanted the prize to be awarded:

The capital shall be invested by my executors in safe securities and shall constitute a fund, the interest on which shall be annually distributed in the form of prizes to those who, during the preceding year, shall have conferred the greatest benefit on mankind. The said interest shall be divided into five equal parts, which shall be apportioned as follows: one part to the person who shall have made the most important discovery or invention within the field of physics; one part to the person who shall have made the most important chemical discovery or improvement; one part to the person who shall have made the most important discovery within the domain of physiology or medicine; one part to the person who shall have produced in the field of literature the most outstanding work of an idealistic tendency; and one part to the person who shall have done the most or the best work for fraternity among nations, for the abolition or reduction of standing armies and for the holding and promotion of peace congresses.