Turned up to eleven: Fair and Balanced

Thursday, May 08, 2003

The first draft outline

Since after a couple of days, I am still interested in doing this, here is a tentative outline of my book

Tentative book title:
Humanity's Invisible Partners: the microbes that bewitch, bedevil, and benefit us


Introduction: We often only pay attention to microbes when they cause us harm (HIV, SARS, Cholera, Malaria, TB, …), and aside from a few well known instances (yeast in beer, bacteria in yogurt and cheese) are ignorant of the positive impacts that bacteria, yeast, and even viruses can have on our lives. Examples abound, in nature, in industry, and in our own bodies. (elaborate)

Part I: The arms race within

Chapter 1: The attacking microbes


Viral diseases

Bacterial infections

Protozoans, Fungi, Int. worms

Chapter 2: The immune response (innate and adaptive)


Innate Immunity

Adaptive Immunity-Humoral

Adaptive Immunity-Cellular

Development of T, B cell repertoire –self v. non-self

Chapter 3: Evolution of immunity, microbes

Microbes evolve quickly (short gen time)

Microbes evolve weirdly (mobile genetic elements)

The immune system is evolved to respond to a rapidly changing attacking force

Part II: Our microbial protectors

Chapter 4: Microbial life on our skin

Benign bacteria protect us from pathogens

Chapter 5: The microbe inside the man

Our ability to digest complex organic material is utterly dependent on the microbes in our guts

The symbionts in our gut microbial flora protect us against attack by food borne pathogens

Reactions of the immune system with microbes in the gut are important for the development of the immune system

Chapter 6: The viruses in your DNA

Human Genome is ~97% “junk”

Amongst that “junk” are retroviruses, which have integrated into our DNA, and “live” there happily, never causing us any harm. The don’t have a well established role in our lives, but the presence of so much “junk” may make it less likely for “real” retroviruses to integrate into important genes. Additionally, the presence of “cryptic” viruses may actually prevent integration of dangerous ones

Part III Our microbial provender

Chapter 7- have some cheese with that wine

Microbial impact on food production-wine, beer, cheese, yogurt…

Chapter 8- Down on the farm is the place to be

Microbial impact on agriculture-nitrogen fixation

Chapter 9- Breathing Oxygen? Thanks, cyanobacteria!

The initial conversion of the atmosphere from mostly CO2 and CH4 to N2 and O2 was done by primitive cyanobacteria and methanotrophic archaea

Even now, production of O2 by photosynthesis is predominated by algae, cyanobacterial mats, and other photosynthetic bacteria- plants and trees are also dependent on their nitrogen fixing bacterial partners for their part, so no matter where you look, bacteria are keeping your atmosphere breathable

Part IV

The Biotech Revolution turns 100

Chapter 10 The founding fathers

Pasteur, Koch, Winogradsky, Ehrlich…The fathers of modern microbiology (probably some others too)


Viruses and Bacteriophages

Chapter 11 The Genetic Revolution

Avery, McCleod, McCarty-DNA is genetic material

Lederberg (and others)

A-T, G-C Chargaff

Watson/Crick (and Franklin, and Wilkins)-the double helix

Jacob and Monod- gene regulation

Chapter 12 Expansion and Acceleration

Recombinant DNA tech

Plasmids, transposons, phage-mobile elements

DNA sequencing


Microarrays and genomics/proteomics

Example of the change-in 1980, cloning a gene would be a Ph.D. project, a lifetime could be spent studying it. I cloned 3 genes, sequenced them, and studied their activity in my modest Ph.D. project (certainly no earthshattering achievements there!)

In 1996 (I think)-full sequence of Hemophilus influenzae was a Science pub. Now, full-sequence and comparative genomics is maybe a PNAS pub at least 100 microbial genomes sequenced, many more on the way (public, probably lots more by drug co’s)

Chapter 13 Here’s to your health!

Microbial Biotech in drug discovery, biotech

Virtually every antibiotic ever made is either produced by a bacterium, or derived chemically from those produced by bacteria (mostly the former)

Many chemotherapeutic drugs (mitomycin C, actinomycin D) are from bacteria

Many, many other drugs are based on “rational drug design”, which relies on knowing the target for the action. This, capability is largely the result of recombinant DNA tech, relying on “transformed” cell lines (using viruses), and purified proteins (usually using bacteria or yeast).

Production of drugs from bacteria, yeast, baculovirus transformed insect cells, etc. Some very effective drugs are in fact proteins produced using the aforementioned recombinant organisms in fermenters

Part V Where do we go from here?

Chapter 14-microbiology marches on

The revolution in recombinant DNA tech and genomics has opened up wide new vistas for microbiologists. PCR allows us to identify bacteria and viruses we can’t grow in the lab (yet). Recursively, knowing the species of an uncultured microbe can help us design media to grow it in. The estimates of species diversity in the microbiota run in the millions, but only a few thousand species have been identified, and even fewer have been cultured. There is plenty of room for more study

Chapter 15-crowd noise

Bacteriology started with looking through microscopes at bacteria in various environments. The development of pure culture techniques made it possible to look at single species in isolation, to our great benefit. This is nowhere near exhausted as a method, but certain very important topics are by definition slighted by pure culture. One of these is growth in a biofilm, which standard pure culture techniques (shake flasks and agar plates) tend to ignore and/or actively discourage. Additionally, bacteria do not live by themselves. They live in communities, and they actively take in information about their surroundings, including physical cues, chemical cues, and specific signals that describe the population of other bacteria around them. These signals have profound effects on the bacterium’s future. The process of quorum sensing is a recently popular mechanism by which nearly all bacteria determine how and when genes are expressed. By looking at mixed communities of bacteria (like in nature), we get ideas about how the competition for resources plays out in more detail, and how bacteria talk to one another.

Chapter 16 How does all of this affect people?

In every facet of human existence, the effects of microbial activity are readily apparent-what we eat, the air we breathe, the illnesses we get, and the cures we use; all of these are directly related to the microbes in and all around us. So clearly greater understanding of microbes is important to improving our lot in life. Some examples-(1) Understanding the biology of bacteriophages has lead to new potential therapies for diseases that are hard to treat with antibiotics. These potential treatments may also have the advantage that bacterial resistance is less likely to spread, because the phage is very tightly targeted to a single bacterium. (note: this is really not a recent development; phage therapy was utilized in the pre-antibiotic era, esp. in Russia, but the rediscovery and refinement of the technique has been important) (2) Bioprospecting-with all of those species out there, and all those genes to study and characterize, many new treatments for disease are likely to be found. (3) Probiotics-not only to bacteria seem to make antibiotics that we can use to treat infection, but so called lantibiotics (antibacterial peptides produced by some bacteria) have been suggested as a method for treating gastrointestinal disease, by replacing harmful gut microbes with commensals or symbionts. A treatment for dental caries (cavities) is already available in Great Britain, using a bacterium Streptococcus mutans that has been genetically altered so that it can’t metabolize dietary sugars into acids that eat away at teeth. (4) Gene therapy-although it has been troublesome thus far, there is reason to hope that gene therapy using attenuated or harmless viruses can be used to cure genetic diseases. (5) Targeted antimicrobial treatments- recombinant DNA technology makes it possible to determine the cause of disease rapidly, and target treatments that kill only the agent of infection, rather than all the bacteria, which will curb resistance development. (6) Enhanced agriculture through microbial biotech- better understanding of bacterium-plant interactions may lead to reduced crop pestilence and enhanced yields by relatively simple techniques (for example, using nutrient ratios to enrich for certain beneficial microbes in the soil. (7) Bioremediation- microbes are capable of degrading virtually any chemical pollutant that has been created by man, and the use of microbes in wastewater treatment is well established. This technology will be used in the future for environmental cleanup of all kinds-We may even be able to use microbes to produce methane, hydrogen gas, and electricity, reducing dependence on fossil fuels