Microbial Hermeneutics - 2

Microbes

In the first post of this series we learned that microbes signal one another, that is, they communicate with each other.

In that post we also covered the issue of signal interpretation, that is, discerning which signals to listen to and how to interpret them.

In this post we will take that a bit further, and discuss the findings of science teams we have not yet considered, to learn that microbes actually communicate via a language all their own.

Their language is composed of molecules as words, molecules which the microbes construct within themselves, then broadcast for other microbes to receive, then interpret and act upon.

The importance of this reality cannot be underestimated.

I say this because one of the types of activity that microbes perform is to shape humans in various degrees, both in physical shape and size, including our brains, as well as to influence and/or control some of our behavior, including activating the most extreme behaviors (see Hypothesis: Microbes Generate Toxins of Power - 6).

The video at the bottom of the post has all the detail, since it is a microbiology science presentation by Dr. Bonnie Lynn Bassler, an American molecular biologist who has been a professor at Princeton University since 1994.

She and her team have discovered the "Rosetta Stone" of microbial languages, and can disrupt their hermeneutical processes, to essentially use propaganda to control, to some degree, the behavior of microbes.

I am providing an index into the video which readers can use to focus on any subject more quickly by moving the guide with your mouse to any desired location for quicker review of particular subjects.

Additionally, a follow-up interview with Dr. Bessler is here.

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Index (time, subject)

00:21 - microbes are oldest life forms on Earth
01:03 - 10 times more microbes than human cells in us
01:31 - 100 times more microbial genes than human genes in us
02:00 - microbes are 99% of our make-up; they keep us alive
02:20 - microbes are vital for keeping us alive and healthy
04:20 - microbes talk with a molecular language
07:50 - quorum sensing (like a census) to know population count
08:20 - Intra species communication (shape of words) dialects
10:50 - microbes communicate with other microbes (multi-lingual)
11:20 - they take a census of all other microbes around them
12:30 - synthetic molecules-words interrupt communication
13:50 - synthetic molecules-words confuse the microbes
15:00 - they have collective, community behaviors
15:20 - microbes made the rules for multi-cellular development
16:00 - microbes invented multi-cellular behavior inside us
17:15 - the team

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Hypothesis: Microbes Generate Toxins of Power - 6

Ancient Microbial Neurosurgeons

I am interrupting the flow of this series to change the expected topic, from a look at stem cells as was intended, to a look at microbial influence on the functioning of the human brain (see The Human Microbiome Congress).

Instead, this post will focus on some experimental and observational data that will bring more focus to this series.

More focus on the effects and affects that microbes have on human behavior.

Before going on into stem cell dynamics, which will still be discussed in a future post, I want to double down on the known science available which strongly supports the general premise involved in the notion that microbes have an affect on our thinking and/or our behavior.

This post will startle you, if previous ones haven't yet.

The bulk of scientific research that has been used in this series, so far, has been from microbiologists who were taking a look at primarily symbiotic relationships human cells have with microbial cells (see On The New Meaning of Being Human).

That involves microbes taking part in the development of our brains in ways that end up helping us as we help them (see Hypothesis: Microbes Generate Toxins of Power - 5).

That cooperation and peace can seem bland in some ways, possibly because of movies, television, and the like, where shoot-em-up bang-bang is the norm.

So, to grab your attention and focus on the earth-shaking reality we are talking about in this series, we will hold off on the discussion of stem cells to instead take a quick look at a parasitic microbe, one that does not have the good manners that symbiotic microbes have.

That parasitic microbe is the protozoa Toxoplasma gondii ("Toxo") which, as a world renowned scientist explains, has incredible abilities:

The parasite my lab is beginning to focus on is one in the world of mammals, where parasites are changing mammalian behavior... Toxo instead has developed this amazing capacity to alter innate behavior in rodents... If you take a lab rat who is 5,000 generations into being a lab rat, since the ancestor actually ran around in the real world, and you put some cat urine in one corner of their cage, they're going to move to the other side. Completely innate, hard-wired reaction to the smell of cats, the cat pheromones. But take a Toxo-

"Complex" Is An Understatement

infected rodent, and they're no longer afraid of the smell of cats. In fact they become attracted to it. The most damn amazing thing you can ever see, Toxo knows how to make cat urine smell attractive to rats. And rats go and check it out and that rat is now much more likely to wind up in the cat's stomach. Toxo's circle of life completed.

... part of my lab has been trying to figure out the neurobiological aspects. The first thing is that it's for real. The rodents, rats, mice, really do become attracted to cat urine when they've been infected with Toxo. And you might say, okay, well, this is a rodent doing just all sorts of screwy stuff because it's got this parasite turning its brain into Swiss cheese or something. It's just non-specific behavioral chaos. But no, these are incredibly normal animals. Their olfaction is normal, their social behavior is normal, their learning and memory is normal. All of that. It's not just a generically screwy animal.

You say, okay well, it's not that, but Toxo seems to know how to destroy fear and anxiety circuits. But it's not that, either. Because these are rats who are still innately afraid of bright lights. They're nocturnal animals. They're afraid of big, open spaces. You can condition them to be afraid of novel things. The system works perfectly well there. Somehow Toxo can laser out this one fear pathway, this aversion to predator odors... Toxo preferentially knows how to home in on the part of the brain that is all about fear and anxiety, a brain region called the amygdala... Toxo knows how to get in there.

Next, we then saw that Toxo would take the dendrites, the branch and cables that neurons have to connect to each other, and shriveled them up in the amygdala. It was disconnecting circuits. You wind up with fewer cells there. This is a parasite that is unwiring this stuff in the critical part of the brain for fear and anxiety... It knows how to find that particular circuitry... Meanwhile, there is a well-characterized circuit that has to do with sexual attraction. And as it happens, part of this circuit courses through the amygdala, which is pretty interesting in and of itself, and then goes to different areas of the brain than the fear pathways... Toxo knows how to hijack the sexual reward pathway. And you get males infected with Toxo and expose them to a lot of the cat pheromones, and their testes get bigger. Somehow, this damn parasite knows how to make cat urine smell sexually arousing to rodents, and they go and check it out. Totally amazing... So what about humans? A small literature is coming out now reporting neuropsychological testing on men who are Toxo-infected, showing that they get a little bit impulsive... And then the truly astonishing thing: two different groups independently have reported that people who are Toxo-infected have three to four times the likelihood of being killed in car accidents involving reckless speeding... Maybe you take a Toxo-infected human and they start having a proclivity towards doing dumb-ass things that we should be innately averse to, like having your body hurdle through space at high G-forces. Maybe this is the same neurobiology... On a certain level, this is a protozoan parasite that knows more about the neurobiology of anxiety and fear than 25,000 neuroscientists standing on each other's shoulders... But no doubt it's also a tip of the iceberg of God knows what other parasitic stuff is going on out there. Even in the larger sense, God knows what other unseen realms of biology make our behavior far less autonomous than lots of folks would like to think.

(A Talk With Dr. Sapolsky). Bingo, remember that this series is about a hypothesis that microbes may be the source of the toxins of power that corrupt the minds of officials who inhabit offices of power.

Part of this working hypothesis has been that the work the toxins do is focused on the human amygdala (see The Toxic Bridge To Everywhere).

We now know that there are symbiont microbes who help us in countless ways, and now we also know that there are microbes that are parasites, that is, they are not concerned with our best interests.

The previous post in this series is here.

Do Molecular Machines Deliver Toxins of Power?

Machines Had To Evolve First

In the search for the origin of the toxins of power, the Toxins of Power Blog has an attitude of "leave no meme unturned", "leave no molecule unturned", "leave no microbe unturned", and of course "leave no stone unturned."

In that regard, we looked at posts that deal with the study of memetics.

That inquiry included a look at historical attempts to establish the discipline of memetics, as well as some suggestions for the future of that discipline, in the context of using those theories in some manner that would aid us in our search for the origins of toxins of power.

After some theoretical fun with memetics, we picked up the microscope and took a look at the utterly astounding world of microbes.

But we had to move along, taking the search deeper, and while searching deeper we ran across a statement by a scientist whose paper flatly said that any complete inquiry into evolution would necessarily include chemistry:

Dr Clarke said: “There are a lot of fundamental questions about the origins of life and many people think they are questions about biology. But for life to have evolved, you have to have a moment when non-living things become living – everything up to that point is chemistry.”

(Putting A Face On Machine Mutation - 2, emphasis added). The word chemistry conjures up beakers, flasks, and people moving around a laboratory in white coats, but it is also, in large part, the study of molecules and atoms (see chemical elements).

A statement by a scientist during that episode of our inquiry caught our attention and set another course for us:

“Our cells, and the cells of all organisms, are composed of molecular machines. These machines are built of component parts, each of which contributes a partial function or structural element to the machine. How such sophisticated, multi-component machines could evolve has been somewhat mysterious, and highly controversial.” Professor Lithgow said.

(Are Toxins of Power Machines or Organisms?, emphasis added). Another paper indicated that a closer look, in that direction, was needed:

Many cellular processes are carried out by molecular ‘machines’ — assemblies of multiple differentiated proteins that physically interact to execute biological functions ... Our experiments show that increased complexity in an essential molecular machine evolved because of simple, high-probability evolutionary processes, without the apparent evolution of novel functions. They point to a plausible mechanism for the evolution of complexity in other multi-paralogue protein complexes.

(Evolution ... a molecular machine, Nature, emphasis added). An interesting article in Wikipedia made a simple statement that helped:

The most complex molecular machines are found within cells.

(Molecular Machine). We then had a very distinct place to focus the search toward a distinct mechanism that generated toxins, and we found one:

Writing in the journal PLoS Pathogens, the team from Queen Mary's School of Biological and Chemical Sciences show how they studied the molecular machine known as the 'type II bacterial secretion system', which is responsible for delivering potent toxins from bacteria such as enterotoxigenic E. coli and Vibrio cholerae into an infected individual.

Professor Richard Pickersgill, who led the research, said: "Bacterial secretion systems deliver disease causing toxins into host tissue. If we can understand how these machines work, then we can work out how it they might be stopped."

(Decoding the Molecular Machine, emphasis added). Bingo, that is a perfect fit for a place to stay and study a while (see also Structure and function of mammalian cilia, where the term "molecular motor" is used).

Future posts will fuse the Microbial Hermeneutics series with the Hypothesis: Microbes Generate Toxins of Power series, so as to fine tune the concept of a molecular machine with a toxin of power generating mechanism.

Microbial Hermeneutics

"What we have here is a failure to communicate" was a famous line uttered in the movie Cool Hand Luke, starring Paul Newman.

In the search for the origin of the toxins of power, we have considered how ideas and memes are communicated, then stored in memory.

We have also considered, at the higher levels of memory, how those memes and ideas can morph in various ways while still there in memory.

Lately, we have been considering some lower levels of brain activity where tiny, unseen components of memes and ideas in memory involve or require microbial signaling and messaging, as well as the proper handling of that microbial communication.

The understanding of thought generation and processing within the brain involves and requires a serious consideration of these most abundant, these tiny, and these unseen components, which microbiologists call either symbiont, or non-symbiont, microbes.

The Toxins of Power Blog's search for the origin of the toxins of power has led to a hypothesis ("The Hypothesis"), after considering just how important those microbes working within us are, especially in terms of their communication with our other cells.

In an ongoing series here on this blog we have hypothesized that one source of toxins of power is microbial signal or message malfunction:

Not only that, The Hypothesis is further condensed to state that a toxin of power is generated in one or both of these processes, within either symbiont or non-symbiont microbes, by way of "bad messaging" during common, constantly ongoing, human - microbe communications.

(Hypothesis: Microbes Generate Toxins of Power). "What?", the most abundant life form which is also the oldest life form, microbes, still experience the phenomenon of a failure to communicate like Cool Hand Luke did?

Concerning this aspect of the subject matter of communication, which we could call the struggle for clear communication, Dredd Blog has discussed human, language-based hermeneutics in the post "Hermeneutics For The Blogosphere" (cf. Modern Hermeneutics).

So in this post, here on Toxins of Power Blog, we will consider the notion of microbial hermeneutics as an aid to improving The Hypothesis.

Upon further research, I actually found an interesting paper, "Mixed Messages: How Bacteria Resolve Conflicting Signals", concerning microbial communication:

Imagine a graduate student with two thesis advisors. One suggests focusing on the experiments. The other suggests some mathematical modeling. What should the student do? The first strategy might involve doing a little of each, effectively ‘‘averaging’’ their advice. Prioritizing one mentor over the other could be a second option. Finally, when the best choice is unclear, it may be best to flip a coin. Bacteria, which live in complex environments, face similar problems and must respond optimally to multiple conflicting signals.

(Molecular Cell, Volume 42, Issue 4, p. 405, PDF, HTML). The Earth is rife with signals and communication, for example, a while back the cherry blossoms in Washington D.C. were blooming at the beginning of February 2012, a month or so earlier than the climate there calls for.

At that same time, around the nation, the ongoing "snow drought" and warm temperatures were sending signals to the flora and fauna which, as it turns out, were confusing communications that affected a proper understanding of what should be done (blossom, sprout, or stay dormant a while longer?).

That is because it can be dangerous when flora and/or fauna receive signals which normally indicate that spring is here, then as a result errantly go into "spring mode", to be later damaged by what is then a surprising, and seemingly untimely cold snap.

Likewise, the most abundant kind of cell in us, microbes, can also receive ambiguous messages, as shown in the paper "Resolution of Gene Regulatory Conflicts Caused by Combinations of Antibiotics", for example when we improperly use antibiotics:

Regulatory conflicts occur when two signals that individually trigger opposite cellular responses are present simultaneously. Here, we investigate regulatory conflicts in the bacterial response to antibiotic combinations.

(Molecular Cell, Volume 42, Issue 4, p. 413, PDF, HTML). The communication is quite complex:

Quorum sensing is the regulation of gene expression in response to fluctuations in cell-population density. Quorum sensing bacteria produce and release chemical signal molecules called autoinducers that increase in concentration as a function of cell density. The detection of a minimal threshold stimulatory concentration of an autoinducer leads to an alteration in gene expression. Gram-positive and Gram-negative bacteria use quorum sensing communication circuits to regulate a diverse array of physiological activities. These processes include symbiosis, virulence, competence, conjugation, antibiotic production, motility, sporulation, and biofilm formation. In general, Gram-negative bacteria use acylated homoserine lactones as autoinducers, and Gram-positive bacteria use processed oligo-peptides to communicate. Recent advances in the field indicate that cell-cell communication via autoinducers occurs both within and between bacterial species. Furthermore, there is mounting data suggesting that bacterial autoinducers elicit specific responses from host organisms. Although the nature of the chemical signals, the signal relay mechanisms, and the target genes controlled by bacterial quorum sensing systems differ, in every case the ability to communicate with one another allows bacteria to coordinate the gene expression, and therefore the behavior, of the entire community. Presumably, this process bestows upon bacteria some of the qualities of higher organisms. The evolution of quorum sensing systems in bacteria could, therefore, have been one of the early steps in the development of multicellularity.

(Quorum Sensing In Bacteria, emphasis added). It would seem, then, that microbial hermeneutics is not only the oldest form of hermeneutics, but is also a very critical and basic form of hermeneutics:

An alternative view is that cells use simpler ‘‘rules’’ to determine
appropriate gene expression levels in response to conflicting signals. But what do these ‘‘rules’’ look like, how complex are they, and to what extent can they be used to predict the response of cells to novel signal combinations?

These issues are increasingly critical throughout biomedical science. Single-cell organisms such as bacteria can live in extraordinarily diverse environments, in and out of hosts, and surrounded by other microbial species and the antibiotics that many of them produce. In this milieu, signal integration abilities are critical to survival. Similarly, in metazoan development, individual signaling pathways rarely work in isolation; rather, cellular responses depend on combinations of inputs from multiple pathways ...

(Molecular Cell, Volume 42, Issue 4, p. 405, emphasis added). Reiterating The Hypothesis, it does not seem to be too much of a stretch to say that toxins of power are possibly a result of message malfunction at this deep level of communication within us, since it is clear that "bad messaging" can and does happen there.

Furthermore, even the misinterpretation of a valid signal, because of inadequate microbial hermeneutic techniques, could have as much of an adverse impact as an improper signal in the first place could have.

Therefore, I also consider the realm of microbial hermeneutics to be a valid suspect as a source for toxins of power.

Before continuing, notice how similar this concept of microbial hermeneutics is to the scenario of a jury receiving mixed, conflicting messages from expert testimony in a courtroom trial.

Like microbes trying to resolve conflicting signals, the jury must use legal, and other, hermeneutics to resolve the conflict between or among experts, even though the jury is not composed of experts (The Pillars of Knowledge: Faith and Trust?).

Since this post is getting to be a bit long, I will close for now.

In the next post of this series we will consider a more complex area of microbial signaling and communication, which is the incredible "cell factories" that are better known as "stem cells."

They certainly seem to be another possible area where toxins of power could be generated, and therefore, should also be considered.

Hypothesis: Microbes Generate Toxins of Power - 5

For a hypothesis to be valid it must be falsifiable, and it must make predictions or explanations which match experimental or other data.

So, near the end of this post, I will propose some follow up research and/or experiments to do just that.

I will also suggest what those experiments and/or research efforts should show, so as to make it easier to test whether or not The Hypothesis is viable enough to pursue further.

But first, let's bring the history of The Hypothesis up to date.

Prions have been eliminated from The Hypothesis as a source for the toxins of power, thus we are left with either microbes or phages as originators of a toxin of power.

We have data that indicate a likely locus or focus point for this origin, which is the brain:

Microbial colonization of mammals is an evolution-driven process that modulate host physiology, many of which are associated with immunity and nutrient intake. Here, we report that colonization by gut microbiota impacts mammalian brain development and subsequent adult behavior ... our results suggest that the microbial colonization process initiates signaling mechanisms that affect neuronal circuits involved in motor control and anxiety behavior.

(Hypothesis: Microbes Generate Toxins of Power, emphasis added). The full import of that research is that, following colonization, communication of various sorts takes place between and/or among human cells and microbes, which impacts the amygdala, and other limbic system areas:

We therefore studied the expression of these genes in the frontal cortex, striatum, amygdala, and hippocampus of GF and SPF mice, by means of in situ hybridization technique. In GF mice, NGFI-A mRNA expression was significantly lower in various subregions of the prefrontal cortex, including the orbital frontal cortex (Fig. 4 A and A′); as well as in the striatum (GF vs. SPF: 329 ± 33 vs. 586 ± 18, P < 0.0001), hippocampus (CA1 region, GF vs. SPF: 258 ± 15 vs. 499 ± 22, P < 0.0001; CA3 region, GF vs. SPF: 166 ± 13 vs. 236 ± 6, P < 0.001; dentate gyrus, GF vs. SPF: 76 ± 4 vs. 113 ± 5, P < 0.0001) and amygdala (GF vs. SPF: 126 ± 17 vs. 212 ± 19, P < 0.01) compared with SPF mice. Similarly, GF mice had significantly lower BDNF mRNA expression in the hippocampus, amygdala (Fig. 4 B and B′), and cingulate cortex (GF vs. SPF: 162 ± 6 vs. 193 ± 10, P < 0.05), which are key components of the neural circuitry underlying anxiety and fear ... Our results suggest that during evolution, the colonization of gut microbiota has become integrated into the programming of brain development, affecting motor control and anxiety-like behavior.

(Hypothesis: Microbes Generate Toxins of Power - 2). The same method that was used to strengthen the appendix - microbe relationship hypothesis of Dr. Parker will work for testing The Hypothesis as well.

The team testing Dr. Parker's hypothesis used existing medical records, so I propose using that same method to test The Hypothesis, as follows:

1 - examine medical records of people who have been exposed to power (presidents, congress members, judges) covering a time when they behaved improperly in their official capacity;

2 - compare those to medical records of people who have not been exposed to power, at a time when those people were behaving properly;

3 - generate data about the differences in brain chemistry, structure, and brain function between the two groups, focusing on the limbic system, especially the amygdala.

NOTE: the reason for analysis of medical records of those exposed to power, during times of improper official behavior, is because The Hypothesis contains a premise that certain good behaviors are anti-toxins to the toxins of power (See: Tables For The Toxins In Power).

If The Hypothesis is correct the NGFI-A mRNA, BDNF mRNA, chemicals, and other factors mentioned above (Hypothesis: Microbes Generate Toxins of Power - 2) should reveal data supportive of The Hypothesis.

The previous post in this series is here.