All Nobel Prizes in 2014 Will be Microbially Themed: The Microbes Guarantee It

So – last year I secretly created a microbiome based spying system that can transmit the thoughts and emails of people who they colonize.  I introduced this community into all the people on the various Nobel Prize committees in order to get information in advance about their plans for the Nobel Prizes. After getting such information, and discovering that the Nobel’s this year were NOT focused on microbes, I then created a microbiome-behavioral manipulation system and re-infected the Nobel committees with this community.  This community forces their host to think about microbes all the time.  All microbes.  All the time.  And thus I am nearly 100% certain that all the Nobel’s this year will be about microbes in some way.

Given that, here are my predictions for the All-Microbial Nobel Prizes.

The Human Microbiome and Methods for Studying Microbial Communities.  Should go to Norm Pace and some other people.  Possibly Jeff Gordon.  Possibly Jo Handelsman.  Possibly others.  Depends on how much the microbes in the committees emphasize themselves versus all microbes.

Vera Rubin for her work on “Dark Matter” since we all know that the key dark matter in the universe is “microbial dark matter”.

Discovery and characterizing of the mechanisms of CRISPRs.  No clue who will get this but it likely could include Jennifer Doudna and Emmanuelle Charpentier and others.

Bill and Melinda Gates and their foundation for their work on global health, especially on protecting from infectious diseases.

Literature: Ursula K. Le Guin in particular for her Wrinkle in Time series and its emphasis is on mitochondria.

Well, since microcredit has already won an Economics prize, I am not sure how this will play out but certainly it will involve some type of microeconomics.  Definitely NOT macroecnomics. I think the most likely winner here is Esther Duflo because of her work on both microeconomic topics and microcredit.

Misleading microbial headline of the month: Bacteria in Brains Suggest Alzheimer’s-Gum Disease Link

Wow.  Check out this story from Bloomberg: Bacteria in Brains Suggest Alzheimer’s-Gum Disease Link – Bloomberg.  The title suggests that there is some connection between Alzheimer’s and Gum Disease.  And so does the story.  Plus check out these other stories:

All based on the same work.  Sounds like a real connection was made in this new work showing a link between bad dental hygiene and Alzheimer’s, and also between the bacterium Porphyromonas gingivalis and Alzheimer’s.  These would both be a big big deal.  After all – tooth decay is something you can do something about.  And if tooth decay causes Alzheimer’s – then – well – we could probably prevent Alzheimer’s.

Sounds awesome.  Was going to go invest in companies that are working on this topic.  Then I made a dreadful mistake.  I decided to look at the paper that all of this is based on: Determining the Presence of Periodontopathic Virulence Factors in Short-Term Postmortem Alzheimer’s Disease Brain Tissue.

Hmm .. that is weird.  The paper does not seem to have anything in it really closely tied to all the claims in the news stories. Here is the Abstract:

The aim of this study was to establish a link between periodontal disease and Alzheimer’s disease (AD) with a view to identifying the major periodontal disease bacteria (Treponema denticola, Tannerella forsythia, and Porphyromonas gingivalis) and/or bacterial components in brain tissue from 12 h postmortem delay. Our request matched 10 AD cases for tissue from Brains for Dementia Research alongside 10 non-AD age-related controls with similar or greater postmortem interval. We exposed SVGp12, an astrocyte cell line, to culture supernatant containing lipopolysaccharide (LPS) from the putative periodontal bacteria P. gingivalis. The challenged SVGp12 cells and cryosections from AD and control brains were immunolabeled and immunoblotted using a battery of antibodies including the anti-P. gingivalis-specific monoclonal antibody. Immunofluorescence labeling demonstrated the SVGp12 cell line was able to adsorb LPS from culture supernatant on its surface membrane; similar labeling was observed in four out of 10 AD cases. Immunoblotting demonstrated bands corresponding to LPS from P. gingivalis in the SVGp12 cell lysate and in the same four AD brain specimens which were positive when screened by immunofluorescence. All controls remained negative throughout while the same four cases were consistently positive for P. gingivalis LPS (p = 0.029). This study confirms that LPS from periodontal bacteria can access the AD brain during life as labeling in the corresponding controls, with equivalent/longer postmortem interval, was absent. Demonstration of a known chronic oral-pathogen-related virulence factor reaching the human brains suggests an inflammatory role in the existing AD pathology.

Alas, even via UC Davis Libraries I do not have access to the full article.  So my inferences will have to be based on the abstract (note to authors, if you want people to judge your full papers not just your abstracts, well, it would be good to have your paper be available).  From what I can tell – what they showed in this paper is that antibodies that are known to find to lipopolysaccharide (LPS) from P. gingivalis showed positive binding to brain material from a few patients who had Alzheimer’s and did not show binding to brain material from controls.  So let’s ask and try to answer a few questions about this:

  • Does LPS from a specific organism in the brain mean that the organism was in the brain: I don’t think so – LPS could move around?
  • Does binding by the antibody they used mean that there is LPS from P. gingivalis there?  Definitely no – there could be cross reactivity with other LPSs or even other molecules?
  • Did they do any more specific tests (e.g., DNA)? Doesn’t seem like it.

But let us just assume that they really did detect P. gingivalis in the brains of Alzheimer’s patients.  Would this mean PG causes Alzheimer’s? Obviously it does not mean that. Let us even assume (ridiculously) that PG causes Alzheimer’s.  Would this mean the periodontal disease leads to Alzheimer’s? No – PG could come into brains in other ways.

I could go on and on.  There are so so so so so so so many jumps that are needed to go from the limited results presented in this paper to getting anywhere near supporting a hypothesis that periodontal disease causes Alzheimer’s that it makes we want to scream.  The news reporting here is awful.  The scientists involved seem to be overhyping their work to extremes with risky, dangerous possible consequences (e.g., – oh – so you have Alzheimer’s – it’s your fault for not taking care of your teeth … we need more money for dental care to prevent Alzheimer’s; everyone should take prophylactic antibiotics to prevent Alzheimer’s and so on).

Guest post: Kevin Carpenter on his new microbial photo exhibit at the Exploratorium in SF #SoCool

Special guest post from Kevin Carpenter who has microbe photos featured at the Exploratorium.

One of my colleagues who does research on the microbes that live in the hindguts of lower termites once remarked that interesting organisms can be found in the most unusual of places. And the lower termite hindgut, by almost anyone’s estimation, is certainly an unusual place. It is also a fascinating place for anyone interested in biology, ecology, evolution, biochemistry, or beautiful natural forms and patterns.

Since my undergraduate days in the early 90s, I have had a deep interest in the tree of life, especially eukaryote phylogeny. After a Ph.D. in Plant Biology at U.C. Davis, I headed off to the University of British Columbia to work in Patrick Keeling’s lab to pursue these interests. Anyone who has this peculiar obsession (actually, I think it’s peculiar not to have this obsession!) knows that the eukaryote tree comprises mostly protists, and they arguably encompass greater structural, cell biological, biochemical, (and certainly evolutionary!) diversity than all plants, animals, and fungi combined.

In Patrick’s lab I developed methods for SEM and TEM imaging of these microbes to investigate their phenotypic character evolution, functional morphology, and symbioses with bacteria in the light of molecular phylogenetic data. In addition to a number of publications (with more to come) and talks in Russia, Germany, Norway, etc. my electron micrographs have been featured on numerous journal covers, textbooks, and invited artistic presentations in Canada and Germany.

On 17 April 2013, a collection of 11 of my scanning electron micrographs of lower termite hindgut protists and their bacterial symbionts will go on permanent exhibit at the Exploratorium museum as they open their new $300 million dollar location on Pier 15 in San Francisco. This is a large (12′ x 4′) installation in the East Gallery (overlooking the bay):

The waterfront location, the architecture, the exhibits, and sustainable technology (rooftop solar panels, etc) are all amazing, and I encourage anyone with any interest in science/biology, art, experimentation, tinkering, and beautiful views to come out for a visit. For more information on the exhibit, the organisms, additional images and other resources (including a blog!), please visit my website at:

As for the organisms…

The hindgut of wood-feeding lower termites–comprising approximately 1000 species (out of a total of several thousand species of termites)–is densely packed with symbiotic protozoa (protists), many of which engulf and enzymatically degrade wood fragments making their way to the termite hindgut. Far from being parasites, numerous studies have shown this to be a mutualsitic symbiosis, by demonstrating that the termites will starve and die if deprived of their protist symbionts. The symbiosis between lower termites and their hindgut protists is one of the longest-studied and best-known examples of microbial symbiosis, dating back nearly a century and a half to the work by Joseph Leidy and others.

The protists are anaerobic flagellates belonging to Parabasalia or Oxymonadida–members of the Excavate eukaryotic supergroup (also including euglenids, trypanosomes, Giardia, and heterolobosean amoebas). There are numerous odd, interesting, beautiful, and instructive things about these protists.

First, they are endemic to termite hindguts and are found nowhere else. Most of the protist species are found only in association with a single species of termite. The termites pass their hindgut biota from adult to newly hatched nymphs and moulting adult termites (which lose their hindgut contents) via specialized feeding behaviors. It is thought that termites evolved social behavior and caste differentiation from their cockroach ancestors partly to pass hindgut protists between individuals.

Second, many of the protist species and lineages have attained large size (up to 300 microns in length), and enormous structural complexity. Some of the protists are estimated to bear up to 50,000 flagella, each associated with specialized proteinaceous structures (kinetosomes, parabasal fibers) inside the cell. Hence, these are likely among the most structurally complex cells known to science. This is in marked contrast to other symbiotic protist lineages such as microsporidia, apicomplexans, and the coral reef symbiont Cyanidioschyzon, all of which have undergone extreme structural reduction. When looking at these termite gut protists in all of their great structural complexity, dwarfing their numerous bacterial surface symbionts, it is is kind of mind-boggling in a sense to realize that this is a unicellular organism!

Third, the cell biology of these organisms is so different from what is taught in undergraduate cell biology (which is really mammalian, or at best, metazoan cell biology), that it may (hopefully) cause one to reflect on how truly diverse and unknown our biosphere really is. As one example of this, in parabasalid protists, mitochondria have become drastically reduced structurally (loss of cristae), functionally (loss of oxidative metabolism/Krebs cycle), and genomically, and their only known function is the conversion of pyruvate to acetate, with the production of hydrogen gas as a waste product. Hence, these relict mitochondria are called hydrogensomes. The oxymonads are among the least understood group of eukaryotes, and for many species it is unknown what they eat (some of the smaller species apparently do not eat wood), how they reproduce, or how they metabolize their food. Some even have a non-canonical genetic code.

The sitution becomes even more complex when we consider the bacteria in lower termite hindgut systems. In light of their importance in the human and other gut microbiomes, it is no surprise that the termite gut is swarming with innumerable bacteria, many of which are likely found only in one species of termite. What is surprising is that an estimated 90% of all bacterial cells in these systems live either on the surface of, or inside of a protist, and are not free-swimming. One study estimates that the large protist Pseudotrichonympha harbors about 100,000 bacterial cells. Microscopy reveals specialized attachment structures that help the bacteria anchor to the protist surface. Our research shows that the large protist Barbulanympha has not only vast numbers of rod-shaped bacteria on its cell surface and interior, but also bacteria surrounding extruded strands of cytoplasm. This is possibly a mechanism to increase the area available for exchange of nutrients.

Recent research on bacteria symbiotic with termite gut protists suggests that they are important in nitrogen metabolism–both in nitrogen fixation and synthesis of vitamins and amino acids. They are thought to transfer these compounds to their host protist (and to the termite) in return for sugars derived from breakdown of wood.

Just as the protists are generally endemic to a single species of termite, in many cases, bacteria found in symbiotic association with the protists are endemic to a single species of protist. Given this close, three-way association between termite, protist, and bacteria, it is perhaps not surprising that evidence of triplex speciation has been found in these organisms: both the bacteria and their protist hosts speciate in tandem in response to termite speciation events. This is one of only a handful of putative cases of triplex speciation.

The symbiosis between termites and protists is actually also present in a species of wood-feeding cockroach–Cryptocercus punctulatus. C. punctulatus is actually more closely related to termites than to other cockroaches (cockroaches are paraphyletic). It is believed that symbiotic protists were present in the hindgut of the ancestor of C. punctulatus and modern termites, which likely lived over 100 million years ago.

Thus, I consider these termite hindgut systems to be among the most unusual, beautiful, and instructive natural laboratories in evolution and ecology known to science. Nature indeed seems to enjoy tinkering, and in that spirit, I think this is well suited to representation in a place like the Exploratorium!

A few references (copied straight out of one of my manuscripts!) for those interested:

Brune, A. & Ohkuma, M. (2011). Role of the termite gut microbiota in symbiotic digestion. In Biology of Termites: A Modern Synthesis, Bignell, D. E., Roisin, Y. and Lo, N. (Eds.), pp. 439-475. London: Springer.

Carpenter, K.J., Chow, L. & Keeling, P.J. (2009). Morphology, phylogeny, and diversity of Trichonympha (Parabasalia: Hypermastigida) of the wood-feeding cockroach Cryptocercus punctulatus. J Eukaryot Microbiol 56(4), 305-313.

Carpenter, K.J., Horak, A., Chow, L. & Keeling, P.J. (2011). Symbiosis, Morphology, and Phylogeny of Hoplonymphidae (Parabasalia) of the Wood-Feeding Roach Cryptocercus punctulatus. Journal of Eukaryotic Microbiology 58(5), 426-436.

Carpenter, K.J., Horak, A. & Keeling, P.J. (2010). Phylogenetic position and morphology of spirotrichosomidae (parabasalia): new evidence from Leptospironympha of Cryptocercus punctulatus. Protist 161(1), 122-132.

Carpenter, K.J. & Keeling, P.J. (2007). Morphology and phylogenetic position of Eucomonympha imla (Parabasalia: Hypermastigida). J Eukaryot Microbiol 54(4), 325-332.

Carpenter, K.J., Waller, R.F. & Keeling, P.J. (2008). Surface morphology of Saccinobaculus (Oxymonadida): implications for character evolution and function in oxymonads. Protist 159(2), 209-221.

Hongoh, Y., Sharma, V.K., Prakash, T., Noda, S., Taylor, T.D., Kudo, T., Sakaki, Y., Toyoda, A., Hattori, M. & Ohkuma, M. (2008a). Complete genome of the uncultured Termite Group 1 bacteria in a single host protist cell. Proc Natl Acad Sci U S A 105(14), 5555-5560.

Hongoh, Y., Sharma, V.K., Prakash, T., Noda, S., Toh, H., Taylor, T.D., Kudo, T., Sakaki, Y., Toyoda, A., Hattori, M. & Ohkuma, M. (2008b). Genome of an endosymbiont coupling N2 fixation to cellulolysis within protist cells in termite gut. Science 322(5904), 1108-1109.

Ohkuma, M. & Brune, A. (2011). Diversity, structure, and evolution of the termite gut microbial community. In Biology of Termites: A Modern Synthesis, Bignell, D. E., Roisin, Y. and Lo, N. (Eds.), pp. 413-438. London: Springer.

Welcome to the Microbial Earth Project

Map of type strains.

All interested in microbes and their genomes should check out The Microbial Earth Project.  It “is an international effort to generate a comprehensive catalog from genome sequences of all the archaeal and bacterial type strains. The name of the project comes from the recognition that Earth is a predominantly a microbial planet, and by effect in order to understand life on our planet, we need to understand how microbial life works.”

There are some 10,000 described type strains of bacteria and archaea.  Not really a lot given that there are probably millions upon millions of species of bacteria and archaea.  But it is what we have available to us in terms of the formally described and accepted species for which there is an available cultured strain.

At this site you can do things like “Adopt a Type Strain” or view a cool “Map of the type strains“.

The Steering Committee for the project is

Much of the real work being done by Nikos Kyrpides, George Garrity, and others though I am very pleased to be a member of the Steering Committee.   One of my key jobs will be to get the word out early and often.  Hence this post.

Germophobia 101: there are microbes on pacifiers; therefore pacifiers cause atherosclerosis & diabetes

Oh my God.  I hope upon hope that the quote in this story was unintended.  The story is from US News and World Report: Dirty Pacifiers May Make Infants Sick: Study – US News and World Report

It is excruciatingly painful to read.  First, the headline is misleading and way out of line.  US News should be reprimanded for this.  There is no evidence presented that pacifiers are making anyone sick.

What is the story about?  At a conference someone(s) presented results of taking used and new pacifiers and chopping them up and seeing what grew on different parts.  And they found – get ready – microbes on them.  And more microbes on the used ones than the new ones.  And they even found some microbes that were apparently resistant to antibiotics.

Scared yet?  You shouldn’t be because of course  Fortunately the story does quote on sane person

Dr. Ben Hoffman, medical director of the Children’s Safety Center at Oregon Health and Science University’s Doernbecher Children’s Hospital, said he can’t think of an infection a child has had that he would attribute to a pacifier. 

“The majority of things you’re going to find on a pacifier are things we’ll find on our clothes, normal human flora,” said Hoffman. “It’s not a reason to demonize pacifiers if people find them useful.”

But alas it also quotes the lead author of the study.

Glass doesn’t recommend that parents use pacifiers to calm their babies and toddlers. “After doing the study, I say why take a risk? The key is to recognize that pacifiers can cause illness,” he said. “In the long run, it may be that what you do now [using a pacifier] may have a lot to do with whether a child ends up developing atherosclerosis or type 2 diabetes.”

What? The? Fu$*#? Pacifiers have microbes on them.  Therefore they cause atherosclerosis and diabetes?   Completely, unbelievably insane and irresponsible.  And I think US News should have made it clearer that this is just completely out of line.

NASA personnel ignore planetary protection guidelines and risk putting microbes on Mars

Many years ago I served on a NASA sponsored committee for a series of meetings about the handling of samples collected from Mars.  One of the key points of discussion at those meetings was “planetary protection”.  The involved protecting Earth from possibly strange life forms that in theory could exist on Mars.  And it also involved protecting Mars from microbes and other life forms that could come from space ships/landers.  I even posted all the materials from these meetings a few weeks ago: Notes and materials from MARS Sample Handling Workshops 2000 ….

It is thus with great distress that I read an LA Times article that reveals that some of the people involved in launching Curiosity decided to ignore some of the planetary protection guidelines and made some hands on modifications that may have contaminated some of the drill bits on Curiosity with microbes from people.  See: If the Mars rover finds water, it could be H2 … uh oh! –

The LA Times reports that some NASA personnel opened a box of drill bits that had been sterilized and – in clean but not sterile conditions – installed one of these drill bits in a drill on Curiosity prior to launch.  Apparently they were worried that a rough landing could prevent the bits from being installable in the drill which would make the drill not be of any use.  And they appear to have now risked the sterility of the entire operation by doing this.  Well crap.  That just plain sucks.  So much effort by “planetary protection officers” and others.  That effort might all go down the drain because of this.  I get that some times things seem urgent and that sure – if the drill was useless people would be pretty upset too.  But this seems to me to be a serious error in judgement.

In a small way I helped develop the guidelines that were put in place to protect Mars from human induced contamination.  And now that seems to have been a wasted effort as the guidelines were ignored.  Not good.

Note – for those interested I have posted links below to the documents from my days at the NASA Mars Sample Handling Workshops.  Most/all are public domain materials but not all are easy to find so I thought I would post them here.  Note – I have done no clean up of scans – will do so at some point. Enjoy

UPDATE 9/13 – some more stories on this
UPDATE 2: 9/13 – UC Davis Prof. Dawn Sumner (who is involved with the Curiosity mission) disputes notion that opening the drill bit box is an issue

Episode of Radio New Zealand "This Way Up": "Meet your microbes" discussion w/ me

Did an interview over the phone with Simon Morton for Radio New Zealand’s “This Way Up.”  Discussing microbial diversity and in part as a follow up on my TEDMED/TED talk.

Future of the human microbiome project (HMP) at NIH?

Just got this question by email

“Dear Professor Eisen, I wonder if you can shed any light on the question whether the Human Microbiome Project will be renewed or if it is being discontinued at NIH. I happened to thumb through (on a Kindle) the 2013 proposed budget for the NIH Common Fund to find to my astonishment that the HMP — which had been lionized in June and July in issues of Nature and Science and PLoS — has been apparently zeroed out. The Budget narrative states bleakly: “The FY 2013 President’s Budget request of $1.207 million for HMP represents a decrease of $22.531 million, or 94.92 percent less than the FY 2012 level. The estimated decrease in funding reflects the planned FY 2012 conclusion of all but one of the awards. This award had a late start, and therefore will continue into FY 2013. There is a possibility of supporting a second phase of the HMP program, pending an analysis of current needs.” If you go on the HMP website, you will see that all the program RFPs have been archived under the statement “There are no funding opportunities at this time.” (See I am an avid follower of your Tree of life Blog. Thank you for running it. I imagine other readers might also be interested in what is going on with respect to the HMP budget. “

Interesting question.  Here is what I know which is very limited.

  • The NIH Human Microbiome Project was funded as a “Roadmap” initiative.  
    • “The Human Microbiome Project is part of the NIH Roadmap for Medical Research. The Roadmap is a series of initiatives designed to pursue major opportunities and gaps in biomedical research that no single NIH institute could tackle alone, but which the agency as a whole can address to make the biggest impact possible on the progress of medical research. Additional information about the NIH Roadmap can be found at”
    • It was a five year program, starting in 2007 and ending in 2012. 
  • The full details of the 2013 NIH budget request are here
  • In 2013 testimony by NIH at congress the HMP is discussed
    • “One fascinating area of basic research is the Human Microbiome Project, an initiative supported through the NIH Common Fund. This project is giving us wonderful insights into the sweeping range of bacteria that live on and in each of us, and is expanding our knowledge about the role of these microbial communities in health and disease. Recent scientific evidence suggests that changes in the composition and activity of the human microbiome may contribute to obesity, which may provide us with new ways of addressing this serious threat to our nation’s health.”
I have heard discussions about how NIH might try to do another round of funding for the HMP but I do not know where this stands.  If anyone out there knows anything else — please post.

Visit to Capitol Public Radio HQ & appearance on "Insight" w/ @CapRadioRuyak

Just got back from a brief visit to Sacramento (which is 15 minutes or so my where I live in Davis, CA). I had a mini 10 minute or so appearance on “Insight” a radio show on Capitol Public Radio.

My visit all started maybe a few weeks ago when I bumped into Lin Weaver in Davis.  Lin was showing some friends of hers around Davis and we chatted for a while on the sidewalk.  One of the topics was my recent fun giving a Tedmed talk.

Anyway – we chatted for 15-20 minutes or so and then I headed home.  And a few days later I got an email from Lin inviting me to be a guest on Insight.  Cool.  I love the show – and listen to it whenever I can.  So I said I had to check some details and then got back to her later and said “yes.”

Lin and the folks at Capitol Public Radio then sent me some additional details and asked for some links to use for their website.

And this AM I headed on in to town.  I was asked to get to their studio at 9:45 AM.  Their studio is on the campus of Sacramento State and I headed on in early and got their at about 9:30.  Of course – I took some pics and posted some stuff to twitter …

Got a parking permit at the desk and then was led into the back of the building to
“The Green Room” and got a look at the studio:


And of course posted to twitter 



I then relaxed in the Green room.  A few minutes before ten the host of insight Beth Ruyak came by.  She instantly made me relax about the interview (was not stressed per se, but somehow felt even more relaxed after the minute with her).  She told me I would be up second and then she left to get ready for the show. 
I took some more pictures and posted a few more tweets


I continued to hang out in the Green Room and got to listen to the interview with the previous guest – Marcos Breton – a reporter for the Sacramento Bee who’s stuff I actually know a little bit of since he covers baseball.

While listening to them chatting away on the air, I decided to add some microbes to the Insight guest book:


And then the assistant producer came out and told me it was almost time to go into the studio.  And then I was in.  Sat down and talked for 10 or so minutes with Ruyak.  We talked about diabetes, microbes, me, twitter, and more. And then it was over.

I took a few pics of the office on the way out:


And that was it.

And it seems it is already on the web.