Why "neglected tropical diseases" are going to bite us in the *$&#

Malaria. Chagas. Filariasis. Dengue fever. Onchocerchiasis. Trachoma. Cholera. Leishmaniasis. Yaws. Leprosy.

Neglected tropical diseases. You certainly don't want to get them (I have had at least one). And they are not as neglected as they used to be with some money being dedicated to them (e.g. from the Gates Foundation) and their own PLoS journal dedicated to them and even famous people blogging about them. The World Health Organization pushes for them to get more attention.

But given that these diseases kill and injure BILLIONS of people and cause untold amounts of economic damage, they clearly still do not get what they deserve, in terms of research dollars and drug development efforts, etc.

Well, listen up people in the non-tropical (a.k.a. developed) world. Even if the "let's help others" line does not light your fire, you better start worrying about these diseases. That is because many of these diseases are on the march in part due to global warming and will likely soon be a bigger part of our life in the developed world.

There has been lots in the press and web about this but it still seems to get ignored which is why I am blogging about it here. For example see

• NPR story from 2002
• Union of Concerned Scientists article
• BBC article from 1999

The thing that reminded me of this issue was a 12/23/07 New York Times article discussing the spread of the tropical virus that causes chikungunya into Europe for the first time.

So, next time you are lingering in Berlin or New York or Moscow and you feel a weird itch. Or have a fever that just won't go away. Or have strange swellings where you never had them before. Don't just look for diseases that were once common wherever you are. Start to think about things like Dengue (my favorite, since I have had it). And maybe just maybe, you should start to worry about these things BEFORE you get them. And support efforts to make these diseases not so neglected.

Happy Hollidays Open Access Movement

Well there is damn good news on the Open Access to scientific literature front. President Bush signed the big spending bill today that includes a provision requiring all papers coming from NIH funded work to be made freely available after 1 year. From the Washington Post:

Under the bill's terms, scientists getting grant money from the National Institutes of Health would now have to submit to the NIH a final copy of their research papers when those papers are accepted for publication in a journal. An NIH database would then post those papers, free to the public, within 12 months after publication.

I am giddy with excitement about this. Congratulations to all who lobbied so hard for this, such as Heather Joseph from SPARC. Her quote from the Post article is helpful here:

"The basic reason we went to bat so hard for this was because we thought it was the right thing to do with taxpayers' science," Joseph said. "Now there will be $29 billion in taxpayer investments freely available to the public," she said, referring to the NIH medical research budget

NIH wants proposals on the human microbiome ...

NIH has an press release regarding the new Roadmap Initiative on the Microbiome. I quote from it below:

Bethesda, Md., Wed., Dec. 19, 2007 – The human body contains trillions of microorganisms, living together with human cells, usually in harmony. Because of their small size, however, microorganisms make up only about one to two percent of the body's mass. Many microbes maintain our health, while others cause illness. Yet, surprisingly little is known about the role this astounding assortment of bacteria, fungi and other microbes play in human health and disease. To better understand these interactions, the National Institutes of Health (NIH) today announced the official launch of the Human Microbiome Project. The human microbiome is the collective genomes of all microorganisms present in or on the human body.

"The human microbiome is largely unexplored," said NIH Director Elias A. Zerhouni, M.D. "It is essential that we understand how microorganisms interact with the human body to affect health and disease. This project has the potential to transform the ways we understand human health and prevent, diagnose and treat a wide range of conditions."

Part of the NIH's Roadmap for Medical Research, the Human Microbiome Project will award a total of $115 million to researchers over the next five years. Initially, researchers will sequence 600 microbial genomes, completing a collection that will total some 1,000 microbial genomes and providing a resource for investigators interested in exploring the human microbiome. Other microbial genomes are being contributed to the collection by individual NIH institutes and internationally funded projects. A meeting between international partners was recently convened to discuss forming an international consortium.

Researchers will then use new, comprehensive laboratory technologies to characterize the microbial communities present in samples taken from healthy human volunteers, even for microbes that cannot be grown in the laboratory. The samples will be collected from five body regions known to be inhabited by microbial communities: the digestive tract, the mouth, the skin, the nose, and the female urogenital tract. Demonstration projects will subsequently be funded to sample the microbiomes from volunteers with specific diseases. This will allow researchers to correlate the relationship between changes in a microbiome present at a particular body site to a specific illness.

"We now understand that there are more microbial cells than human cells in the human body. The Human Microbiome Project offers an opportunity to transform our understanding of the relationships between microbes and humans in health and disease," said Dr. Alan Krensky, the director of the Office of Portfolio Analysis and Strategic Initiatives (OPASI), which oversees the NIH Roadmap for Medical Research.

While the term "microbiome" may be relatively new in biomedical research, most people are familiar with some of the effects - both good and bad - that microbes can have on our health. Consider the example of the biggest reservoir of microbes in humans: the digestive tract. The human gut harbors many beneficial microorganisms, including certain bacteria called probiotics. There is evidence these probiotics, found in dietary supplements, yogurt and other dairy products as well as various soy products, can stimulate the immune system and improve digestive functions. In contrast, previous research suggests that variations in the composition of microbial communities may contribute to chronic health conditions, including diabetes, asthma, obesity and digestive disorders.

"Microbes play a significant role in the health of the digestive tract and many digestive diseases result when the microbial environment is out of balance," said Griffin P. Rodgers, M.D., M.A.C.P., director of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and co-chair of the Human Microbiome Project's Implementation Group. "The Human Microbiome Project will help us better understand the microbial environment in the gut, as well as provide us with the tools and technology to expand our exploration into this field of research."

Traditionally, microbiology has focused on the study of individual species as isolated units, making it difficult to develop and inventory all of the microbes in and on the human body. Because their growth is dependent upon a specific natural environment, it's difficult to recreate microbe-host interactions in the laboratory. Advances in next generation DNA sequencing technologies relying on a process called metagenomic sequencing will be used. Instead of isolating each microbe, all of the DNA within the collected samples will be sequenced.

"Our goal is to discover what microbial communities exist in different parts of the human body and to explore how these communities change in the presence of health or disease," said National Human Genome Research Institute Director, Francis S. Collins, M.D., Ph.D., co-chair of the Human Microbiome Project Implementation Group. "In addition, we will likely identify novel genes and functional elements in microbial genomes that will reshape the way we think about and approach human biology."

NIH recently awarded $8.2 million to four sequencing centers, to start building a framework and data resources for the Human Microbiome Project. One-year awards were given to the sequencing centers at the Baylor College of Medicine, Houston, and Washington University School of Medicine, St. Louis, which are part of the NHGRI Large-Scale Sequencing Research Network; and the Broad Institute of MIT/ Harvard, Cambridge, Mass., and the J. Craig Venter Institute, Rockville, Md., which are funded through the National Institute of Allergy and Infectious Diseases (NIAID) Microbial Genome Sequencing Centers Program.

The objectives of this initial work are to sequence the genomes of 200 microbes that have been isolated from the human body as part of the 1,000 microbial genomes collection. Researchers will also begin recruiting healthy volunteers who will donate samples from the five body regions. NHGRI, NIAID, and the National Institute of Dental and Craniofacial Research (NIDCR) have led the initial phases of the project.

"The recent emergence of faster and cost-effective sequencing technologies promises to provide an unprecedented amount of information about these microbial communities, which in turn will bolster the development and refinement of analytical tools and strategies," said NIAID Director Anthony S. Fauci, M.D., co-chair of the Human Microbiome Project's Implementation Group.

Following the precedents set by other large-scale genomics efforts, such as the Human Genome Project and the International HapMap Project, data from the Human Microbiome Project will be swiftly deposited in public databases, including those supported by the National Center for Biotechnology Information (www.ncbi.nlm.nih.gov/mapview), part of the National Library of Medicine. The project also will fund the establishment of a Data Analysis and Coordinating Center, which will coordinate data access and develop data retrieval tools for the research community.

Also following on the lead of those efforts, the Human Microbiome Project will monitor and support research on the ethical, legal and social implications of the research. Areas of focus include the clinical and health implications of using probiotics, potential forensic uses of microbiome profiles, bioterrorism and biodefense applications, the application of new technologies from the project, and patenting and privacy issues.

"Examining and addressing the emerging ethical, legal and social implications of metagenomics research is central to our goal of one day moving any resulting diagnostic, prevention, or treatment tools into the clinic in a safe and effective manner," said NIDCR Director Lawrence Tabak, D.D.S., Ph.D., co-chair for the NIH Human Microbiome Project Implementation Group.

Additional information about the Human Microbiome Project is available at www.nihroadmap.nih.gov/hmp. For more information about funding opportunities, go to: www.nihroadmap.nih.gov/hmp/grants.asp. A high resolution image of the bacteria, Entercoccus faecalis, a microbe that lives in the human gut, is available in color at www.genome.gov/pressDisplay.cfm?photoID=20023, or in black and white at www.genome.gov/pressDisplay.cfm?photoID=20024.

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 www.nihroadmap.nih.gov.

The National Institutes of Health (NIH) -"The Nation's Medical Research Agency" - includes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

Though I risk introduce more competition for myself here I thought I would add some key links to the calls for proposals:


* Development of New tools for Computational Analysis of Human Microbiome
Project Data (R01)
* (RFA-RM-08-008)
* NIH Roadmap Initiatives
* Application Receipt Date(s): February 15, 2008
* http://grants.nih.gov/grants/guide/rfa-files/RFA-RM-08-008.html
*
*
* Development of New tools for Computational Analysis of Human Microbiome
Project Data (R21)
* (RFA-RM-08-009)
* NIH Roadmap Initiatives
* Application Receipt Date(s): February 15, 2008
* http://grants.nih.gov/grants/guide/rfa-files/RFA-RM-08-009.html
*
*
* Development of New Technologies Needed for Studying the Human Microbiome
(R01)
* (RFA-RM-08-010)
* NIH Roadmap Initiatives
* Application Receipt Date(s): February 15, 2008
* http://grants.nih.gov/grants/guide/rfa-files/RFA-RM-08-010.html
*
*
* Development of New Technologies Needed for Studying the Human Microbiome
(R21)
* (RFA-RM-08-011)
* NIH Roadmap Initiatives
* Application Receipt Date(s): February 15, 2008
* http://grants.nih.gov/grants/guide/rfa-files/RFA-RM-08-011.html

Phylogenomics makes the big time --- University of Manitoba seeking a "Chair" in Phylogenomics

Now I know Phylogenomics has hit the big time.

University of Manitoba is looking for a chair in the emerging area of phylogenomics. See below. PS - Good job phylogenomics. You have made it.


From their ad:

UNIVERSITY OF MANITOBA – CANADA RESARCH CHAIR – TIER II
Phylogenomics Chair, Department of Biological Sciences, Faculty of Science
Position # 06661 and 06662

The University of Manitoba is seeking applications or nominations for a Canada Research Chair established by the Government of Canada to enable Canadian Universities to foster world-class research excellence (http://www.chairs.gc.ca). Our Strategic Research Plan (http://www.umanitoba.ca/admin/vp_research/research_chairs.html) identifies a Tier II Chair in the Faculty of Science in the area of Phylogenomics as a priority.

The emerging field of Phylogenomics uses an exciting comparative approach to research that integrates the study of the evolution of species using genomic data and the study of genome function using phylogenetic data, and can powerfully inform a broad spectrum of biological research

Performance enhancing drugs - I confess

Yup, that is right. I took steroids today. I hope this does nto rule out my chances of getting into the hall of fame. But hey, I am going to be up front about it so I wanted to post here in case there is a future investigation into performance enhancing drugs among scientists.

What I took was cortisone, by injection for tendinitis in my fingers. The shot, given by a doctor, hurt like nothing else. But I needed it to recover from an injury. This injection hopefully will let me return in a few weeks to "normal" in terms of my typing. And I am sure all of you out there will be happy about that.

So - the question is - am I cheating? Or is using steroids to recover from an injury OK (see Andy Pettite). What if I got the steroids to make my typing faster. Would that be cheating?

Survival of the fittest M&Ms

Fantastic evolution post on the best of Craigslist.

The post starts off with

Whenever I get a package of plain M&Ms, I make it my duty to continue the strength and robustness of the candy as a species. To this end, I hold M&M duels.

And then, after a crushing test of fitness

Occasionally I will get a mutation, a candy that is misshapen, or pointier, or flatter than the rest. Almost invariably this proves to be a weakness, but on very rare occasions it gives the candy extra strength. In this way, the species continues to adapt to its environment.

Then the winning M&M is sent to Mars with a note

Please use this M&M for breeding purposes.

Best part - Mars sent him a coupon for free M&Ms which he considers "grant money." Who said evolution can't be fun.

Thanks to Michael Eisen for pointing this out.

Fired for (not believing in evolution) promising to do sucky science

The Boston Globe reports on a story about a post doc (Nathanial Abraham) from Woods Hole Oceanographic Institution who was fired recently, apparently because he does not believe in evolution. Apparently, even though Abraham was supposed to focus on comparative and evolutionary studies in the lab of Mark E. Hahn, at some point Abraham told Hahn he did not believe in evolution.

This raises the question - that the Globe asks

"Can people work in a scientific field if they don't believe in its basic tenets?"

I think the answer in this is a bit slippery. If someone does not believe in evolution, but in their work still uses evolutionary analyses and perspective I am not sure what one should do. But Abraham apparently went further and said he would not even discuss evolution in papers on the project. This is reflected in a letter from Hahn quoted in the Globe:

". . . You have indicated that you do not recognize the concept of biological evolution and you would not agree to include a full discussion of the evolutionary implications and interpretations of our research in any co-authored publications resulting from this work," Hahn wrote in the letter, which the commission provided to the Globe. "This position is incompatible with the work as proposed to NIH and with my own vision of how it should be carried out and interpreted."

This then becomes more than "not believing" in evolution outside of work. This is clearly a stance that could jeopardize the quality and integrity of the papers coming out of the project (imagine if I said I was going to write all genome papers from now one based on my belief that DNA is not the material of inheritance but instead that membranes are).

So this looks like a case where the issue is much clearer than in some other cases reported recently. Abraham basically was telling his boss "I vow to do sucky science." And for this, I think it is perfectly reasonable that he got canned.

PS - Thanks for Iddo Friedberg for pointing this story.

Also - see PZ Myers' post about this for much more detail.

Sharpshooters, dual symbioses and new ways to sequence a genome

Those interested in symbioses and in new sequencing methods should look at a paper that just came out in PNAS by John McCutcheon and Nancy Moran (OK - I am a bit biased - this work is related to something I did previously with Nancy). Their paper reports a further dissection of a dual symbioses in sharpshooters (a group of insects that feed on xylem sap). The dual symbioses involves two types of bacteria that live inside specialized cells in the gut of these insects.



Previously, my group had worked with Nancy to sequence the genome of one of the symbionts (Baumannia) as well as part of the genome of the second one (Sulcia). Nancy was interested in this symbioses for many reasons including that as obligate xylem feeders the sharpshooters almost certainly were not getting gall the nutrients they needed in their diet. Based on what was known about bacterial symbionts in other sap feeding insects (e.g., aphids) it seemed likely that the symbionts of the sharpshooters were making the missing nutrients for their host. However, all previous genomic based studies had been done on phloem feeding insects like aphids. Phloem and xylem are the two main circulatory systems in plants. Phloem tends to be nutrient rich, although still not rich enough for the aphids to live on it alone. Thus the aphids rely on bacterial symbionts to make amino acids missing in the phloem.

Xylem is generally much poorer in nutrients and this Nancy wanted to compare the genomes of the symbionts of xylem feeders with those of phloem feeders. Nancy and others had done preliminary work on the sharpshooters showing that they had multiple symbionts living inside cells in their gut and that one of the symbionts (which she named Baumannia after Paul Baumann who she had worked with previously) was closely related to the Buchnera symbionts found in aphids.

So Nancy approached me when I was at TIGR and asked if I would be interested in helping her sequence the Baumannia genome. I said yes (secretly, truth be told, I would have tried to sequence the genome of a rock if Nancy asked. She is perhaps the smartest person I know in all of science and is always doing the coolest types of research. Plus, I figured, I might also be able to interact with her husband, Howard Ochman, who also does cool stuff).

Of all the possible sharpshooters (the symbionts are found in all sharpshooters), Nancy chose to focus on the glassy winged sharpshooter because it is an important pest organism (it is a vector for Pierce's disease in grapes).


So - we (well, the core facility at TIGR under my supervision) sequenced the Baumannia genome using DNA that Nancy had isolated from dissections of the gut of glassy winged sharpshooters. In analysis of the genome we (well, again, the royal we --- in this case Dongying Wu in my lab did most of the analysis) found, among many things, that Baumannia appeared to be making vitamins and cofactors for the host. But alas, we also found something missing --- Baumannia did not appear to be able to make amino acids for the host. Since xylem was likely to be missing amino acids that all animals require in their diet, we had figured that Baumannia must be making them for the host. So we were vexed.



That was, until Nancy pointed out (or reminded us - since she probably had mentioned it before) that there was another symbiont living in the gut of these insects --- a symbiont called Sulcia. She suggested that we look at the DNA sequence pieces that did not assemble with the Baumannia genome and look for any that might encode genes similar to genes from the group of bacteria in which Sulcia is found. And, 1.5 years later, after much informatics and lab work, we obtained about 130 kb of the genome of this second symbiont and found that it encoded at least some of the essential amino acid synthesis pathways that could make the needed amino acids for the host. And we stopped there, published a paper in PLoS Biology proposing the existence of a dual symbiosis with one symbiont making vitamins and cofactors and the other making amino acids, and moved on to other things.

Now in this new paper, Nancy's lab has returned to this symbioses and has finished the genome of Sulcia (the genome is available here in Genbank). And the story just gets cooler and cooler. With this complete genome they get a more detailed picture of the symbiosis than we were able to obtain, and are able to really reconstruct the whole system (and correct some mistakes we had made in our paper). My favorite thing in their paper is Figure 3 which you can find here (I am not sure about the PNAS policy of putting the image in my blog since this does not seem to be an Open article). This figure shows their reconstruction of what could be called to community metabolism. Interestingly it appears the symbionts depend on each other and are not just passing things on to the host separately.

Another important aspect of their paper is that it is the first (as far as I know) example of a genome being finished using a combination of the two hot new sequencing methods - 454/Roche and Illumina/Solexa. Basically they used the Roche/454 method to provide deep coverage of the Sulcia genome and then used Illumina/Solexa sequencing to get accurate sequence data for the types of sequence for which the Roche method does not work well.

So - check out the paper in PNAS. You won't regret it.

An interactive Tree of Life (Web Tool)

Thanks to Michael Ferrari who has pointed out a cool new phylogenetics visualization tool called the "Interactive Tree of Life"

Put out (I believe) by Peer Bork's group, this tool allows users to upload their own trees and then view and manipulate them from anywhere. Seems like Peer is trying to become the Google of phylogenetics.

Wanna sequence a microbial genome? Try applying to this NSF-USDA

Contrary to rumors that I had heard (and I confess was spreading too) the NSF and USDA have announced the continuation of their Microbial Genome Sequencing program. This is by far and away my favorite grant program pretty much ever. I have gotten funding for most of my favorite projects through this program. So - I hate to bring in competition, but I thought I should post an announcement here:

Microbial Genome Sequencing Program FY2008
As a collaborative, interagency effort, the National Science Foundation (NSF), and the Cooperative State Research, Education, and Extension Service (CSREES) of the U.S. Department of Agriculture invite research proposals (i) to support high-throughput sequencing of the genomes of microorganisms, and (ii) to develop and implement strategies, tools and technologies to make currently available genome sequences more valuable to the user community.

Full Proposal Deadline: February 19, 2008

The link for the solicitation should be up later today at:
http://www.nsf.gov/publications/pub_summ.jsp?ods_key=nsf08511

Personal Genome Project seeking volunteers

The Personal Genome Project is seeking volunteers. The project would sequence (at least part of) your genome. In exchange you would agree to have the data released openly and also have some data about you released as well. I think it this could become a phenomenal medical resource and I am happy some people are volunteering for this. I probably would not do it myself - mostly out of concern for the privacy of my children and relatives. But hey - if you want to do it - all the power to you. Go to their website to sign up.