Most people think germs on their bodies are a Bad Thing. If they didn't, hand sanitizers, disinfectant soap and bleach would not sell so well. As we learn more about the microbes that inhabit our bodies, we are realizing that the human being is really a superorganism composed of about a trillion human cells and 10 trillion microorganisms. Rarely a microbe will cause illness, but these are transient residents that the body actively removes. Most other microbes that live on us are benign and a significant number of them are critical to our good health.

In the latest issue of Science magazine, Torsten Olszak et. al describes how the microbes we come in contact with as children stimulate natural killer cells (part of the immune system) assisting in their development. Without this contact, the natural killer cells do not develop tolerance and can precipitate immune-related diseases such as irritable bowel syndrome and asthma. This contact must occur during childhood for tolerance to develop.

For over 100 years microbiologists have known, to their great consternation, that in any given environment, at least 90% of all microbes are unculturable. In the last few decades, we have developed molecular tools to see these microbes in the environment and determine their presences and number, but we still cannot bring them into culture. There are all sorts of ideas for why this might be true. Many of these microbes may be slow growing, and the fast growing microbes easily outpace them in laboratory medium. Maybe the media we use is "too rich" for many microbes and we need to create media with more dilute nutrients to capture these shy microbes. Maybe the metabolic demands of these microbes were too difficult to replicate in the laboratory and many of them will not grow. Whatever the reason, as of right now, we are nearly blind when it come to these unculturable microbes.

Just this week, what I believe will become a landmark paper, was published in Applied and Environmental Microbiology. Buerger et. al created a simple, elegant experiment to try to capture the slow-growing bacteria. Sediment from the ocean shore of Massachusetts Bay was diluted and then dispensed into wells of a microtiter plate such that each well received only 1 microbe per well. The growth medium used was 0.1x LB medium, a dilution of a common, rich medium. The plates was carefully wrapped and placed in a humidified chamber for 18 months. Yes, that is a 1.5 year experiment! Periodically the plates were checked for growth and any well showing growth was then characterized.

Topoisomerase I unwinds the DNA during cell replication and is an enzyme that is found in Archaea, Bacteria, and Eukarya. Most every living thing has a homolog. To everyone's surprise, it is possible to create mutations that completely remove the activity of the enzyme, yet have cells capable of growth. These cells are sick, but they can grow. The latest research by Stockum et al. shows that these deletion mutants of topoisomerase I actually have compensating mutations, and in fact loss of topoisomerase I is lethal. This makes much more sense.

Norovirus is a nasty little virus that causes tons of misery every winter. It is an RNA virus that infects the gastrointestinal tract causing violent vomiting and diarrhea. About 12 to 48 hours after being infected, rapid symptom onset will lay you flat for about a day. Even better, immunity to this virus fades in a few months and you are susceptible to a new attack. A particularly nasty strain of norovirus has been circulating in my area and my family came down with it just this weekend. The virus is highly contagious, with only 10 virus particles ingested in the mouth being able to cause disease. Much to my surprise, neither my son nor I became ill. This got me wondering why? Follow the link to learn the answer to this story.

All the ducks are in a row, all the t's have been crossed and we have tied up all the lose ends. It's not very often you get a sentence with 3, count them 3, cliches, but it was needed to celebrate the official release of the 4th edition of Through the Microscope.

You can get full access to Through the Microscope in 2 ways.

1. Purchase a subscription to the web site by going to PayPal. This, in my opinion, is the best way. If you want to read parts of the web site on paper, you can always print them out.
2. If you like, you can also get a hard copy of Through the Microscope from lulu.com This is a black and white version of the website. Purchase of the hard copy of the book provides a free subscription to the website. However, you still have to register for the website and then request authorization. You can request authorization by going to the contact form. You will need to provide proof of purchase of the hard copy, namely your lulu receipt.

For full instructions go to Buy this Book.

The eBook is also now complete. This is available to all subscribers to the website. To obtain the eBook, purchase a subscription to the website by clicking on the PayPal button. Once you have paid for a subscription at PayPal, come back to Through the Microscope and log into the site.* Once you are logged in click on the Download Ebook link in the Main Menu to download your copy of the eBook in epub format (compatible with iPad and many other readers) or mobi format (for use on the kindle).

*To verify that you are logged into the site, look in the upper right of the site and look for a LOGOUT link. If it says LOGIN, you are logged in and should have access to the downloads page.

I have completed work on the web site and the book is now live. The Table of Contents has links to all the sections of the textbook. Chapters 1, 2, 3, 15, and 16 are open to the public. Subscribers can view the entire 4th edition. I am working on the paperback textbook and ebook that you can purchase from lulu. At this moment, no book is available from lulu, as I don’t want students buying the old edition. Enjoy!

Work continues on the textbook. Many late nights and vacation days have been spent getting the book refreshed and ready for the next round. A total of 23 chapters have been added to the text and are already available to subscribers of the textbook. With only 5 chapters left to revise, it’s time to start talking about what else will be added to the text.

1. A forum will be added to the site to allow students to ask questions and get them answered by the author of the textbook
2. An ebook compatible with iPad, Kindle, and any other electronic book reader that is compatible with the ePub format will be created. The ebook is DRM-free, meaning you won't have any hassles with digital rights management software getting in the way of you enjoying your purchase
3. A print version of the text will also be available at lulu.com.

I hope you are as excited about the new edition as I am. OK you probably aren't, but it's gonna be awesome!

This past summer and fall I have been working on the new edition of Through the Microscope and it is now taking shape on the web site. If you are a subscriber, you can already have access to the new edition as it is being built — yet another advantage of this effort being primarily a web textbook. Every part of the text was examined for effectiveness and relevance. Some chapters only went through minor editing changes, while others are in the process of being completely rewritten. You can check out the growing Table of Contents.

Both the content of the text and the organization were examined.

A study of pap smears by Julia Brotherton and Dorota Gertig (among others) has shown that the HPV vaccine is decreasing the occurrence of precancerous cells in young women. In contrast to other vaccines, where the benefit is immediately observable, since HPV causes gential warts and years later potentially cervical cancer, it was thought it would be up to a decade before a discernible effect was seen. This study was undertaken 3 years after the HPV vaccine became widespread in Australia in girls 12 to 26 and has shown a halving of the rate of high-grade abnormalities in pap smears. Encouraging news, but more data will be needed before a definitive conclusion can be reached.

Hemorrhagic E. coli causes a nasty gastrointestinal infection that afflicts at least 73,000 patients yearly in the United States. During a recent outbreak of the illness in Germany, doctor Franz Schaefer reported successfully treating a patient with eculizumab, a drug that inhibits the complement system. Recent research suggests that the complement system may be involved in Hemolytic Uremic Syndrome, and inhibition of complement could possibly prevent death from HUS. A young girl suffering from HUS, was treated with eculizumab and showed marked improvement in 24 hours. If this turns out to be true, it would be a *#*$ big deal (as our Vice President likes to say) as HUS is a major cause of death in hemorrhagic E. coli infections.