Teddy's Rat Lab

NEWS: Behind the headlines

2012-02-12T14:00:00.000-08:00

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Many times I am asked by friends - particularly writers - to comment on sensational headlines in Medicine and Biology. Examples are recent columns on the "dangerous super flu" (http://teddysratlab.blogspot.com/2011/11/on-research-ethics.html) and the follow-up (http://teddysratlab.blogspot.com/2011/12/this-just-in-again.html), marijuana treatment of autism (http://teddysratlab.blogspot.com/2011/07/medical-marijuana.html), peer review (http://teddysratlab.blogspot.com/2011/05/future-of-science.html). There are many more that I have answered in personal emails and other discussion forums.

Usually when I am asked one of these questions, I first read the headline article, then look for the referemnce to the actual scientific study. I then read the study and try to find out what else has been done in the field.

Sometimes I go to Wikipedia. GASP! "NO," you say, "not that!" Well, it's true. Many research departments have encouraged graduate students to update Wiki articles with references to their professors' research. You have to treat it with a bit of skepticism, because Wiki authors have biases that blind them to countervailing viewpoints, as well as the obvious (do they ever, just ask Stephanie Osborn!), and there is a tendency to disbelieve anything that the inner circle doesn't originate. However, wiki articles that contain citations to primary material are a good source... of citations to primary material. It's a starting point, but you should always do your own investigation.

Well, now there is a tool to help you do just that!

The U.S. National Institutes of Health provides a website called "PubMed Health: Behind the Headlines" (http://www.ncbi.nlm.nih.gov/pubmedhealth/behindtheheadlines/). Doctors, researchers and students around the world probably know PubMed as the gateway to the NIH's National Library of Medicine. A massive database originally called "Medline" provides the ability to track down just about any biomedical article published (in English) since 1966. In the last 10 years, PubMed has allowed anyone - not just librarians - to search Medline and many associated databases. More recently, NIH/NLM started using PubMed to fulfill its public education mission, with articles and news of general interest.

Interestingly, "Behind the Headlines" is not a U.S., product, but comes from England's National Health Services. Many of the most sensational medical-related headlines seem to appear in The Guardian, The Sun, The Daily Mirror, The Daily Mail, so it is somehow appropriate that "Behind the Headlines" comes from those very same shores.

What this site does, is take current medical headlines apart, showing what is told in the news article (and how it frequently differs from the sensationalist headlines), where the story came from, and what kind of an article it references (i.e. original research, news release or opinion). When the original source is a research article, it takes time to explain the results, what they mean... what they don't mean, and what conclusions the authors drew from the research.

The founder of Behind the Headlines - Sir Muir Gray - very clearly states the rationale behind the site as "“Scientists hate disease and want to see it conquered. But this can lead to them taking an overly optimistic view of their discoveries which is often reflected in newspaper headlines." [Actually, I have found that most scientists really don't like talking to the press, and that most headlines are written by university PR departments. The disconnection from the actual science is one reason why articles featuring synthetic drugs that could never be found in a cannabis sativa leaf get headlined "Medical Marijuana cures..."]

I've researched a couple of recent news stories - particularly one that seems to claim a looming "flesh eating bacteria" epidemic. Behind the Headlines, we find that the actual science said that some of the types of drug-resistant bacteria found in hospitals seem to have traded virulence for resistance to drugs. Thus the really powerful bugs "in the wild" (i.e. in public) can be easily treated with antibiotics, while the drug-resistant bugs in hospitals and nursing homes really don't spread easy between patients. That's a big difference from the headline.

So give it a try, next time you see a news article with a confusing or sensational claim, check out Behind the Headlines and learn the real science.

The GUIDE: Treating Alzheimer's Disease

2012-02-10T14:00:00.000-08:00

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The plain truth of the matter is that there is no cure for Alzheimer's Disease (AD). If neurons in the brain could be grown and replaced like skin, muscle or liver cells, then it might be possible to regrow the lost brain cells, but unfortunately, just replacing cells is not enough - our memory, everything we have learned, and even our very personality is a product of the connections between neurons that have built up over a lifetime.

Image Copyright Alila Sao Mai, 2012
Used under license from Shutterstock.com

What we can do is to support the functions of the undamaged neurons while the symptoms of AD are still mild. In the previous blog is was mentioned that neurons using acetylcholine (ACh) seems to be preferentially affected by AD. Whether the disease specifically targets these neurons or they simply happen to be prevalent in the first brain areas affect is immaterial. What happens is that as acetylcholine neurons die, the amount of signal they can represent is decreased, somewhat like listening to a music player radio with dying batteries. The brain is highly redundant, and most neural signals are carried by multiple neurons. Thus if we could find a way to boost the signal of the remaining neurons, we might be able to delay the debilitating phase(s) of AD.

In the diagram at right, I show a typical "synapse" between neurons. At the top is the "presynaptic neuron" which is the one sending the signal. At the bottom is a portion of the "post synaptic" neuron which receives the signal. Signals in the brain are represented as the distribution of electrical energy - similar, but not exactly like the digital "bits" of a computer. However, in order to cross the gap between neurons, that electrical signal is converted to a chemical one. The positive electrical potential that results from activity in the presynaptic neurons causes release of a stored chemical - the neurotransmitter. The neurotransmitter diffuses into the space between neurons, and when it encounters the neurotransmitter receptors on the postynaptic neurons, it causes the protein to change shape, quite frequently opening a channel that allows positively charged molecules into the neuron. Accumulating positive charge starts the entire process of electrical activation again in the new neuron and the process repeats with transfer of signal from neuron-to-neuron.

The neurotransmitters are short lived - there are enzymes which break them apart, as well as means for the presynaptic cell to reabsorb the components. The reason is that neuron-to-neuron signals should be short, otherwise the information will get lost in continuous signal. But, if the signal is getting weaker due to AD, it makes sense to boost it by prolonging the action at the postsynaptic neuron.

There are a few classes of drugs that can perform that action - the most prevalent drugs - donepizil (Aricept), rivastigmine (Exelon) and galantamine (Razadyne) all work by stopping or slowing down the breakdown of ACh. They are useful to "boost the signal" that naturally occurs by prolonging the activation of the postsynaptic neuron. A second method would be to raise the background activity at ACh receptors by supplying a small amount of an ACh-like drug so that the ACh released by neurons would be more effective in activating the post-synaptic neurons. While much work is ongoing in this field, no drugs of this type are currently in any but experimental use. A third method is to reduce some of the other, "competing" activity in the brain, particularly in areas in which there are many ACh and glutamate neurons. Mematine (Namenda) blocks one type of glutamate receptor, thus producing a "quieter environment" for the ACh neurons. As a last resort, once AD patients start to show symptoms of personality disporders, aggressiveness, hallucination, etc., those symptoms can be treated with antipsychotic drugs.

It should be noted that all of these treatments are symptomatic ones, and they nothing can "cure" or reverse AD. However, there is hope in that supporting memory, decision-making and other activities of the brain can slow the progress of the disease and postpone the onset of more symptoms. There is an old saw about "use it or lose it" and it appears to be true - using the brain strengthens the synapses between neurons. Strong synapses deteriorate slower, and while starting Aricept or other treatment after the onset of AD won't bring back lost function, it will help to maintain what remains.

By the way, vitamins and gingko biloba have no effect on the onset or progress of Alzheimer's disease, no matter what any source may say. No effect means no effect. Obviously a good diet is important, and omega-3 fatty acids and antioxidants are important to normal brain health, so certainly include them (within reason) in your daily intake.

Ideally, as stated above, we should find a way to replace the neurons, remove the amyloid plaques, or fix the neurofibillary tangles. In fact, there are stem cell therapies designed to supply the glial cells that normally support the active neurons. Replacement of neurons may have some benefit, but as stated above, they would need to be "taught" with all of the experience of a lifetime.

Perhaps what is really needed is a science fiction nanomachine that can selectively break up beta-amyloid and fix neurofibrillary tangles. Then we could move on to more nanomachines that rebuild the lost synapses and restore memory from a previous template.

Hmmm. Where have I heard that before?

The GUIDE: What is Alzheimer's Disease?

2012-02-08T14:00:00.000-08:00

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This post gets directly at a question asked a couple of weeks ago, in terms of exactly what Alzheimer's Disease (AD) is in terms of a neural disease. Knowing what the actual disease process is, coupled to a discussion of what brain areas and neuron types are affected, will help to explain many of the effects.

To start out, I am going to bring back the illustration from last blog, and explain what is going on.

PubMed Health. A service of the National Library of Medicine, National Institutes of Health.
Illustration URL: http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001767/figure/A000760.B8681/?report=objectonly

In short, AD is a disease in which certain types of neuron die due to an accumulation of proteins that are normally broken down and metabolized. Instead of being broken down, the proteins accumulate both within neurons and "plaques" of dead and dying cells. These dense masses also exert pressure on other neurons and cause problems due to impaired blood and circulation and "lymph" flow (in brain, it's not really lymph, but a thinner, filtered electrolyte solution called "Cerebrospinal Fluid").

I will digress for but a moment - many if not most cells in the body are round or squarish shapes, but neurons have long branches called dendrites (from the Latin for tree) and even longer axons which connect neurons together in a manner similar to electrical wiring. Forming and maintaining this shape requires an internal structure, and that is provided by very fine filaments and tubes called, unsurprisingly,neurofilaments and neurotubules. These structures form what is common called the "cytoskeleton" and are responsible not just for holding the cell's shape, but for providing a transportation pathway for movement of chemicals throughout the neurons. Under normal circumstances, the neurofilaments consists of polymer chains of a protein called "Tau." In the AD brain and certain other neural disorders, Tau proteins do not assemble properly, and the neurofilaments become tangled and random. These tangles can be seen when the brain tissue is examined under a microscope, and excess Tau can be detected both in the AD brain and in tissue where cell damage has occurred. Thus it is not entirely clear whether the AD-affected neurons make too much Tau, or simply that excess Tau is available due to death of neurons and attempts to make more and appropriate neurofilaments for the neurons.

The membranes of cells in the body consist mostly of lipid molecules with a few proteins floating in the lipid. Think of how a soap bubble forms, trapping air inside of a thin film of detergent, with swirls of color and pattern in the soap. Now think of the appearance of oil on water. That same swirl of color indicates that a thin film of oil - lipid - is dispersed over the surface of the water. Shake the mix, and you will see tiny bubles of oil, some with water trapped inside.

Cells are like that, a thin film of lipid, with water and proteins on the inside, salt water on the outside, and proteins plus complex oily molecules (triglycerides and cholesterol!) to stabilize the film of lipid into a membrane. One of the stabilizing proteins that is particularly important to forming the synapses which connect neurons, is amyloid precursor protein (APP) is important, but when excess APP is produced, it can be broken down into fragments of "beta-amyloid" which are insoluble and difficult to metabolize. Deposits of beta amyloid accumulate and essentially "choke" neurons. As neurons die, the beta-amyloid remains and builds up, leaving "plaques" and dead neurons in the brain in place of healthy neurons.

AD is characterized by the presence of neurofibrillary tangles - indicating cells that are nonfunctional or dying - and plaques, indicating large ares where many neurons have died. Neurons do not regrow, and the accumulations of Tau and beta-amyloid are dense, so the total brain volume shrinks. Once this process occurs, the symptoms match the brain areas most affected - temporal lobe plaques are associated with memory problems, frontal lobe with decision-making and movement planning, parietal and occipital lobe with sensory inputs and hallucinations, the "basal nuclei" with movement disorders and all of the above.

Thus the many symptoms of AD can be explained by examining the progress of the disease - AD tangles and plaques typically show up in temporal lobe, then parietal/frontal lobes and finally thalamus and the deep nuclei - resulting in amnesia, then personality changes, difficulty making decisions, and gradual worsening of all of the above.

An additional consideration that had neuroscientists chasing in the wrong direction for a few years is that the initial stages of the disease appear to preferentially affect that neurons that use acetylcholine for neurotransmitter. You may recall that there the most common chemicals associated with communication between neurons are (in order of prevalence)glutamate, gamma-amino-butyric acid, norepinephrine, and acetylcholine (ACh). ACh does double duty by also being the neurotransmitter that is present in muscles and forms the junction between motor nerve (for control of muscles) and the muscle itself. ACh is also very prevalent in the hippocampus, and is associated with memory storage and recall processes. AD was origianlly thought to be a disease solely of ACh neurons, and thus could be treated much the same as Myasthenia Gravis - a disease of the ACh receptors in muscles. Alas, AD affects all types of neurons, but the presence of many ACh neurons in the hippocampus associated with the early symptoms of the disease do make it a candidate for treatment drugs.

The next blog will discuss treatment and therapeutic options, and perhaps provide a bit of hope for the future in the treatment of AD.

Thanks for reading.

The GUIDE: "Whatizname's Disease"

2012-02-06T14:00:00.000-08:00

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Alzheimer's Disease.

This is the big one. I have actually put writing this segment off as long as I could due to the complexity of the subject. It will also probably take more than one post to do justice to the topic. SO, you have been warned!

In a list of top 10 questions that many Neuroscientists are asked about the brain, one of the following questions: "What is Alzheimer's Disease?" "What causes it?" and "How can we treat it?" will usually be in the top three.

Right from the top I am going to admit that I need help with this one. I know the effects, the symptoms and what happens, but there is so much more to the topic, that I need an expert resource for assistance. Fortunately, the U.S. National Institutes of Health feel the same way, so the National Library of Medicine, via its "PubMed" database, has help for you and me on the subject. So, I acknowledge considerable help from the Alzheimer's disease page of Pubmed Health (http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001767/).

I will start with my personal encounter with the disease. In 1979, I was a recent college graduate lookign to go to medical school to study Neurology or Neurosurgery. My grandmother was in her 70's and started showing signs of senile dementia. Alois Alzheimer had identified the disease process in 1906, but it wasn't until the 60's that researchers linked the Alzheimer's brain cell abnormalities to cognitive decline and memory loss. By 1979, the term "Alzheimer's Disease" was starting to be heard by the American public. My aunts immediately latched onto AD as the explanation for my grandmother's problems, but I wasn't so sure. AS understood in 1979, AD was presenile dementia, meaning it hit at a much earlier age than "normal" senility. Many of the known cases of AD at that time were in patients of age 50-70. I felt that claimed AD for my grandmother was stretching the definition, but I would certainly do some research to find out.

It turns out that I was right and wrong. My grandmother had actually suffered a "psychotic break" we didn't realize it at the time, but she had undergone a severely stressful experience that caused her to withdraw from normal social interaction, while at the same time appearing to lose the inhibitions that normally keep a person from acting on impulse. Still, over the years, as AD was better understood, and as we watched her deteriorate, it became apparent that she did indeed have a steady decline in mental abilities and memory, thus whether she had AD in 1979 was a moot point, she certainly had it in later years. Instead of going to medical school for a clinical Neuro specialty, I obtained a doctorate in Neuro research - at a medical school, so I did take many of the same classes - and I specialized in memory, which brought me face to face with Alzheimer's Disease on many occasions.

So, to finish off today's blog, I'll discuss the two main types of AD and what they are. For the next couple of blogs I'll talk about diagnosis, treatment, and the research being done on AD.

AD can only be accurately diagnosed by looking directly at the brain tissue and neurons. That means that autopsy is really the only way to be certain, but brain scans such as CT and MRI may show damaged areas in advanced cases. "Early Onset AD" is the "presenile" type that I was familiar with in 1979. The symptoms typically appear before age 60, it runs in families, and the course of the disease is very fast. Early onset AD often leads to death in a few years. "Late Onset AD" typically shows up after age 60, and in many ways is not very different from classical "senility." In fact, there are some who argue that all humans would get AD if they lived long enough. This form of the disease may also run in families, but the genetic component is not very clear.

Many doctors and neuroscientists view AD as a multi-step process as in the figure above. A third type of "pre-AD" called "Mild Cognitive Decline" frequently occurs as patients age and develop difficulty retrieving some memories or making certain decisions. The onset of MCI is often in the 50's prior to the age when such memory difficulties are "normal" (i.e. late 70's and older). The decline continues until a threshold is reached - at any age - and frank AD symptoms are seen, accompanied by a rapid loss of memory and cognitive ability.

Symptoms: (again I am indebted to Pubmed Health)

Dementia usually first appears as forgetfulness, then changes in emotional behavior or personality, mild aphasia, changes in perception, then impairment of thinking and judgment. The precursor stage - MCI - appears with the difficulty in doing more than one task at a time, inability to tune out distractions, difficulty solving problems, forgetting recent events or conversation, and constantly restarting or taking longer to complete difficult activities. AD itself is characterized as difficulty learning new tasks or performing old tasks that used to be easy, getting lost in familiar places, extreme aphasia and difficulty with language or understanding, mood changes and loss of interest, loss of social skills. As AD gets worse, these symptoms impair the ability to take care of one's self, result in inappropriate actions, depression, irrationality, hallucination, and eventually loss of memory, inability to speak or understand speech, inability to recognize family members, loss of control of bodily functions.

Alzheimer's disease is a sad, heartbreaking condition for families, and it is not a matter to be taken lightly, hence my reluctance to cover the subject until now.

I'll be back over the next few blogs to discuss more of the brain science behind AD and to give some hope for future scientific developments in this field.

Until then, take care of your brain... please.

NEWS and a REVIEW: Quantum theory, photons, sanity and science fiction

2012-02-05T14:00:00.000-08:00

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For SuUper Bowl Sunday, this is SUPER NEAT stuff! Scientists create light from vacuum (http://www.physorg.com/news/2011-11-scientists-vacuum.html). Quantum physics is confusing stuff. It has been said that if a person actually understands it, they should immediately roll a SAN check (a roleplaying game player's term for rolling dice to determine whether you've gone insane)! I don't pretend to understand QP, but I do read about it, and I have friends that understand it (and yes, their sanity can definitely be questioned at times - then again, one of them is an SF author!).

This article is neat because it actually demonstrates a theory that has been in existence for over 40 years - that the vacuum of space isn't really empty, but that there are "virtual" particles that are neither here nor there until forced into existence. Think Schroedinger's Cat - you don't "really" know what state the cat is in until you look in the box. In quantum terms, the cat actually exists in multiple states at once - the same with particles in vacuum - they exist as in potentia until observed. Understand? Make your SAN roll...

So here's the scientific reference:

Observation of the dynamical Casimir effect in a superconducting circuit" C. M. Wilson, G. Johansson, A. Pourkabirian, M. Simoen, J. R. Johansson, T. Duty, F. Nori, & P. Delsing, Nature 479, 376–379 (17 November 2011), doi:10.1038/nature10561

The neat thing about the experiments at Chalmers University of Technology (Gothenburg, Sweden) is that the found a way to make vacuum particles change from a "virtual" state to one that can actually be observed - in this case, the particles are photons, and the light from these photons can be observed appearing out of vacuum.

The 42-year old theory that predicted the experiment stated that since photons travel at the speed of light, a mirror moving at nearly the speed of light would transfer some of it's own energy to virtual photons, making them appear as pairs of real photons. In the experiment, the Chalmers scientists substituted a superconducting quantum interference device (aka, a "SQUID") for the mirror and "vibrated" it a nearly 25% of the speed of light by rapid switching magnetic fields. The result, called a demonstration of the "Dynamic Casimir Effect" produces photons, since photons do not have measurable mass, they require the least energy to create - other particles such as protons would require transfer of a lot more energy.

Neat stuff indeed, and one step closer to a future in which making something from nothing just requires the right technology and lots of energy.

Which brings us to this week's SF book review: "Guardian of Night" by Tony Daniel (Baen Books). The reason for tying the NEWS and REVIEW posts together, is that the science of Guardian of Night relies heavily on SQUIDs and quantum physics. The future is not too distant, where Earth was forced into rapid development by a war with an alien species which either enslaves all of its enemies. Humans are resourceful, however, and have reverse-engineered much of the alien technology and managed to hold their own for over a decade.

However, during that time, the alien "sceeve" have been distracted, dealing with internal dissent and insurrection. They've settled their internal problems and taken a good hard look at "those pesky humans," deciding that Earth is too dangerous to enslave and needs to be exterminated. The sceeve are sending a fleet with a novel weapon to finish the job, but they hadn't counted on one of their own deciding to defect.

Fans of "The Hunt for Red October" will find familiar ground in this novel. It is said that the best science fiction is that which successfully files off the serial numbers of an existing idea and adapts it to a new, exciting story. Author Tony Daniel has certainly done so with this book, the adventure is first rate, and the familiarity with the premise actually helps the enjoyment of the book - it is by no means an exact copy, and the climax of the book, along with believable, likable characters is great.

This book is definitely HARD Science Fiction, the highly advanced human starships are hardly physical creations at all, but manifestations of virtual quantum particles held together with SQUIDs. The navigation through space utilizes quantum uncertainty in a manner that actually allows a ship to almost be in two places at once during a critical battle. The alien creatures are a bit far-fetched, but the author sketched in only enough detail to let our minds fill in the rest, and didn't try to make all of the pieces fit.

I thoroughly enjoyed this book - it is a good premise and makes a fine story. However! And it's a big one - this is a blog about science, and uses a lot of complicated terminology - but I try not to abuse my readers with it, and I use (and define) only what is necessary to explain. Unfortunately, there is a near-fatal flaw in the writing style of this book. Mr. Daniel - I hope you are reading this - I loved the story, but you thoroughly abused your readers with jargon.

The book starts out using no less than 13 futuristic, alien and pseudo-scientific jargon terms with absolutely no references to allow the reader to understand them. I am no fan of extensive infodumps, but seriously, Tony, you needed some. From the very start of the book, we had an exper monitoring the beta for signs of the sceeve. The exper was functioning in chroma and interacting with geists and servants. Transmission from the alien vessel weren't transmissions, but conditioning beta. Ships and signals traveled through Q but then certain devices and constructs were also materialized out of Q. Back on Earth we find that Earth had been attacked by churn and the remnants - curd - are still around, causing problems. Members of the Extry in ships made of Q bottles are attempting to decode alien beta conditioning and decide what to do about the alien fleet approaching through the Q. Civilian and military leaders are meeting with the President with part of their interaction occurring via salt which enables them to see geists, servants and information in chroma. This is not science, it is throwing out jargon terms in the hopes that someone will think that it is science.

Granted, the reader eventually gained enough context to get some, if not most of the terms. Many of them are explained in infodumps about two-thirds of the way through the book, but it seriously took about a third of the book to get contextual meaning (for example, the sceeve have no discrete brain as such, but have a distributed nervous system like an invertebrate - however, they are symbiotic life forms, and one of those symbiots is the gid which serves as a personal and racial memory).

I am used to jargon. I have to use it all day long; however, I have been burned professionally with scientific papers that have been rejected for too much use proprietary terms and jargon. If Science can declare a hiatus from jargon, perhaps we need to do the same for Science Fiction. Again, I thoroughly enjoyed the premise and the story, but I am afraid that some readers will hit the jargon, realize there is no immediate explanation, and drop the book. If they've paid prime prices for a physical book, they may even decide to reject other writings from this author and publisher. That would be a shame, so I figure I need to be upfront in this review and suggest that the reader hang in for the rest of the story.

Guardian of Night by Tony Daniel will be released in paperback next Tuesday, Feb. 7 at Amazon and is available now in every conceivable electronic book format at Baen eBooks (http://www.baenebooks.com/s-255-tony-daniel.aspx).

The GUIDE: Brain Basics, a reprise

2012-02-03T10:41:00.000-08:00

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As promised, I am reblogging this post from about a year ago in which I covered many of the basics of brain function. I prefer to describe brain function in terms of:

(A) Input
(B) Output
(C) Processing
and
(D) Control

Clearly "Output" and "Control" could be thought of as the same thing, but I will clarify that in my classification scheme, "Output" results in an action of the body, while "Control" results in a change to the body's internal workings.

Now, what are the "Inputs"? Vision, Hearing, Smell, Taste and Touch. Those are the five basic senses. In addition, there are special cases: "Proprioception," the sense of body and limb position is a special case of "Touch," although the receptors are in the joints and muscles and not the skin. Balance is tightly associated with the sense of hearing, but is controlled mostly by proprioceptors, pressure sensors on the feet, and the proprioceptor-like neurons of the semicircular canals. Smell and Taste are essentially the same sense - what we sometimes call "Chemoreception" - and there are special instances of chemoreception through skin receptors. This brings us to pain. The sense of Pain is closely intermingled with all of the senses, each can signal a painful stimulus, but for the most part it is organized with, and associated with the sense of touch.

Outputs: The commonly considered outputs of the brain are speech and muscle movement. In truth there are many more outputs, but most of them fall into regulating the various physiological systems of the body, and are more appropriately considered "Control" functions. In addition, muscle movement is not just moving the limbs, but also includes eye blinks, pupil dilation and constriction, "scanning" movements, adjustments of the ear drum, swallowing, breathing, and piloerection (goosebumps).

Processing is the function that involves the largest percentage of the brain. Once a sensory neuron reports to the appropriate part of the brain, that information is *represented* then *associate*. Smell gets associated with taste, and we decide which foods we like. Sound and vision are associated, and we can track a moving car, bird, airplane, or that baseball flying toward us at 75-80 mph. Vision, touch (vibration) and proprioception are associated, and we are certain we've *hit* that baseball out of the park. Vision, hearing, and proprioception are associated to give us the power of speech and reading.

Memory is processing; as is "executive function" or decision-making.

Control functions take two forms - what we call the "autonomic" - and you can substitute the word "automatic" - functions, and coordination. Taking the latter type first, coordination usually involves association between the Input and Output functions. Vision plus eye movement (and pupil dilation) provides tracking. There is a brain area that performs precisely those functions. Proprioception plus muscle movement plus vision plus the sense of touch is necessary to coordinate the smooth muscle movements necessary to reach out - *find* the object we are reaching for, stop the hand, grasp the object, and move it to another position. Autonomic functions include resting heart rate, breathing rate, body temperature, blood pressure, hunger, fear, excitement, and even mating.

To reiterate from a previous blog, the diagram of the various "lobes" of the brain at right also serve to divide up functions as well. If one were to draw a line directly downward from the point marked "Central Sulcus," most Input functions would be to the right and Output to the left. Red (Frontal), Orange (Cerebellum), and light Blue (Brainstem) are Control areas. Blue (Parietal) and Yellow (Temporal) are Processing areas, although there are also some processing in the Frontal lobe.

Over the next several blogs, we will continue to discuss diseases and disorders of the brain. This organization is important to being able to understand many of the "central" brain disorders such as Alzheimer's disease, and the "A's" as posted last week. It's been long enough since the original post that I thought it worth repeating both for new and continuing readers.

In the meantime, protect your brain it's the only brain you've got!

The GUIDE: A Mental Exercise

2012-02-01T11:59:00.000-08:00

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Every so often, I am asked a question that triggers an idea. That idea percolates into more thoughts, and the next thing I know, I find myself almost compelled to write something. In this case, a blog entry, about why writers feel so tired despite sitting at a computer all day with "minimal" exertion.

Image Copyright Dyonisos Design, 2012
Used under license from Shutterstock.com

In her blog today, my friend* [*OK, so really, she's almost family, but that's complicated, and she's a friend, foremost.] Sarah A. Hoyt blogs that lately she feels so tired from writing - as if she has been running in a hamster wheel all day (link: http://accordingtohoyt.com/2012/02/01/running-in-the-hamster-wheel-of-the-mind/). This has triggered discussion on her blog and on Facebook about the concept of "Mental Exercise" and how a person can feel tired just from activities that are almost exclusively mental.

In response, my mental exercise goes "Blog Post!" so here goes:

First, I'd like to say to the Facebook commenters that they are essentially correct - the brain consumes more than 1/4 of the "energy" of the body each day - that energy being in the form of glucose in the blood, ATP (the energy transport molecule) produced in cells, and oxygen. Muscles can store both oxygen (the myoglobin molecule in muscle is what gives red meat its characteristic color) and glucose (as the complex molecule glycogen, and as fatty acids). What physiologists call "fast-twitch" muscle, uses its own stores to quickly respond before the rest of the body can adapt to supplying blood and oxygen. Fast-twitch equates to sheer strength and sprint-like speed, but endurance requires the heart to pump and the lungs to exchange O2 and CO2 more efficiently to deliver oxygen and glucose to the "slow-twitch" (or "white-meat") muscles than can continue exertion for hours.

The brain is effectively "slow-twitch." It does not have the capability of storing either glucose or oxygen, so in the absence of muscle exertion or digesting a very large meal, the brain is the largest "customer" for oxygen and glucose. In fact, Neuroscientists and doctors take advantage of this fact when doing functional brain imaging. MRI is typically used to scan for the hydrogen molecules in water, and are able to develop detailed images of soft tissues of the body because of differences in water content. However, if the MRI is adjusted to scan for oxygen, we can develop pictures of the function of the brain on the basis of the flow and usage of oxygenated blood to the most active brain regions over a period of just a few minutes. We call this type of imaging "functional MRI" and it is just one of the techniques now being used to study detailed brain function in humans, although without the fine detail we can get from electrodes which can record the activity of single brain cells. Another imaging technique - Positron Emission Tomography (PET) - relies on the usage of glucose by using "2-deoxyglucose" (2-DG) which is glucose minus the second -OH group that allows it to be broken down in brain and muscle cells. For imaging, one of the two hydrogens where the -OH was removed is replaced with the briefly radioactive isotope fluorine-18, forming "18fluoro-2-deoxyglucose" or FDG. A very small amount of FDG is injected into the blood, and it is taken up normally by cells that need glucose - such as active brain areas. The FDG can then be detected by a scanner, and provides a map of the most metabolically active areas of the brain (or the body - it is used to map metastatic cancer, as well).

So, the brain really does use up a lot of the energy that the body produces - it has to, since it doesn't really make that much on its own - but what about this idea of "mental exercise?" To answer that, I will use the example of dreams. During the "rapid-eye-movement" phase of sleep (see the Dreams blog: http://teddysratlab.blogspot.com/2011/02/dreams-story-in-brain-so-what-really-is.html), the brain is active, associating information and comparing with new and stored memories.We typically call that "dreaming," and scientists have shown that many parts of the brain are active during dreaming, especially the parts that control muscles. Since we can't see another person's dreams, scientists rely on waking a subject up and questioning them about what they dreamed - leading to the understanding that dreaming of physical activity actually activates the parts of the brain that cause the activity. The signals from the brain never quite reach the muscles thanks to a "switch" in the thalamus that blocks the signals. However, not every signal goes through this switch, and activity dreams result in many small twitches of the muscles that would be moving if the subject was awake and actually performing their dreams. Thus it really is possible for a person to "dream all night and wake up tired" because their muscles really did work during their dreams.

Getting back to Sarah's complaint of being tired just from writing, though - how does writing tie in to dreams? Well, one of the fascinating things about the human brain is that we can imaging movements and motions. Martial arts and many forms of active training require the participant to imagine the movement before actually doing it. Thinking about an action, still involves all of the same brain areas as doing the movement, just as in dreams. This is a critical feature in learning accuracy and effective movements, but it is also the key principle in how advanced neural-based prosthetics operate. "Bionic" limbs, as I will discuss later this month, rely on reading the pattern in the brain that results from a patient thinking about a limb movement, even when that limb is paralyzed or amputated. In fact, patients can't help but think about moving limbs, and scientists can detect those patterns in the brain, and in tiny muscle twitches in the affected limb. The normal human that imagines movement has that same brain activity and same tiny muscle twitches. A writer working on an action scene with any shred of detail or accuracy is imagining the motions and activities of that scene. As their mental image of activity unfolds, the muscles of their body go through those activities, just not enough to consciously move.

It's why we hold our breath during tense moments, why the parent of a teen driver wears out the passenger floorboard with the brake pedal that isn't there, why we are so touched by a good love scene, or why the person playing "Angry Birds" tilts their phone (and whole body) to get that last block to fall even when they know it will have no effect on the final outcome.

Mental exercise. It's not enough to condition muscles or lose weight, but it does involve brain activity, and can produce tiredness despite apparently sitting still. The brain and the body feel that they have been active,and that's where the sense of tiredness comes from.

So, yes Sarah and the other writers out there, you have been exerting yourself as you sit and write. It may just seem like dreams and imagination, but to the brain and the body, it is quite real.

-s2la

The GUIDE: Brain and Brain - reprise

2012-01-30T14:00:00.000-08:00

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Classic line, from classic Star Trek. "Brain and brain, what is brain?" This comes from "Spock's Brain", in which we discover that it you just connect the vocal chords, the patient can direct you in connecting the rest of the nerves! In the interests of helping writers avoid such unscientific gaffes (and having those who know better laugh at them, at best, or stop watching/reading, at worst), I created this blog and the current project "The Lab Rats' Guide to the Brain (a guide to 'getting the science right' for writers and readers of science fiction)."

Back in the dim mists of antiquity - in other words, not quite a year ago, I started blogging The Guide, one column at a time, and posted this brief orientation to the overall structure of the brain. To assist new readers and provide continued reference to trhe parts of the brain I figured I should reprint this blog and the "Back to the Basics" blog.

In order to discuss the parts of the brain, I will tell people to hold their left hand at arm's length in front of their face, fingers together, palm flat and facing directly away from the face. To get the full effect, it also helps to imagine that hand in a baseball glove or catcher's mitt, but for now, just compare the hand and the picture at the right. The thumb is the temporal lobe (light blue in the picture) and that's where a lot of the structures that process sound and help us make memory are located. Fingertips are the frontal lobes (purple). That's the control of muscle movement is located andwhere a lot of decision-making and "conscious thought" seems to take place. Neuroscientists call that "executive function" and it is mainly the conscious control of other brain functions. The outside edge of the hand is the parietal lobe (green). there's a lot of sensory structures there. The forward edge of the parietal lobe is the main "somatosensory" (touch, vibration, hot, cold, pain, and position) strip and it is organized according to the different parts of the body. Directly opposite in the frontal lobe is the "motor strip" which controls voluntary muscle movement throughout the body. Down toward the temporal lobe are areas that handle speaking and reading. The occipital lobe (dark blue) is about where the heel of the hand would be in our model. It is almost exclusively related to vision and visual functions. However, some visual processing areas are also in the parietal lobe, since seeing quite frequently connects with hearing, speaking and reading. The cerebellum (red) and brainstem (dark green) are equivalent to the wrist - in many ways. The cerebellum coordinates muscle movement throughout the body, and the brainstem connects the brain to the body (via the spinal cord).

It seems almost as if for every function on the *outside* (surface) of the brain (we call it the "cortex" or "neocortex"), there's a structure deeper within the brain that acts as a relay, switch or preprocessing junction. By the way, we often call the deep structures "nucleus" or "ganglion", or even "fiddly bits" (with apologies to Howard Tayler), although many have their own names such as "thalamus," or "hippocampus."

Also, for those of you following this blog with interest, after the reprise of the Basics, I'll continue with diseases and disorders with Alzheimer's disease, Myasthenia Gravis, Multiple Sclerosis, ALS, deafness, blindness, paralysis and finish up with a discussion of prosthetics and bionics. Feel free at any time to post questions. I'll try to collect them and come back with some "mailbag" posts in a few weeks - just write them in the comments section, or email them to Teddy at TeddRoberts dot com. I might even let the LabRats out of their cages to assist.

Until next time, take care of your brain, it's the only one you've got.

NEWS: Failure of the Imagination.

2012-01-28T12:42:00.000-08:00

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On this day in history... January 28, 1986... Space Shuttle Challenger was lost with all hands. As with the Apollo 1 fire of January 27, 1967 (and why does no-one comment on those dates), this disaster was a failure of the imagination (as spoken by astronaut Frank Borman to Congress in April, 1967) - failure to imagine that all of the conditions would conspire to cause the one-in-a-billion failure.

Yet Americans pushed onward, because freedom isn't free, and Space Exploration comes with a price. Today we face yet another failure of the imagination, because we have a generation that cannot imagine how space exploration can benefit them, as they sit in front of their TVs receiving signals from satellites in space, playing games and making facebook and twitter comments via computers that were developed to miniaturize for space applications, using cell phones with more computing power of the entirety of NASA Mission Control in 1967, surrounded by household materials such as velcro and plastics first developed for the space program.

On a hot summer day in 1962, President John F. Kennedy, speaking at Rice University in Houston extended to this challenge to the American people:

... the vows of this Nation can only be fulfilled if we in this Nationare first, and, therefore, we intend to be first. In short, our leadershipin science and industry, our hopes for peace and security, our obligationsto ourselves as well as others, all require us to make this effort, tosolve these mysteries, to solve them for the good of all men, and to becomethe world's leading space-faring nation.
...
We choose to go to the moon. We choose to go to the moon in thisdecade and do the other things, not because they are easy, but becausethey are hard, because that goal will serve to organize and measure thebest of our energies and skills, because that challenge is one that weare willing to accept, one we are unwilling to postpone, and one whichwe intend to win, and the others, too.

But Kennedy also forsaw the costs, the dangers, and those who would say we cannot afford to spend money on a Space effort

Surelythe opening vistas of space promise high costs and hardships, as well ashigh reward.
...

We have had our failures, but so have others, even if they do notadmit them. And they may be less public.

To be sure, we are behind, and will be behind for some time in mannedflight. But we do not intend to stay behind, and in this decade, we shallmake up and move ahead.

The growth of our science and education will be enriched by new knowledgeof our universe and environment, by new techniques of learning and mappingand observation, by new tools and computers for industry, medicine, thehome as well as the school.

Unfortunately, we live in hard economic times. We have skilled workers out of work, have lost manufacturing jobs to overseas, failed financial institutions and loss of confidence in government. We live in "an age of limited choices" as predicted by Niven, Pournelle and Flynn in their novel Fallen Angels. Yet there is great promise in space effort - already by 1962 there was evidence:

And finally, the space effort itself, while still in its infancy,has already created a great number of new companies, and tens of thousandsof new jobs. Space and related industries are generating new demands ininvestment and skilled personnel, and this city and this state, and thisregion, will share greatly in this growth.

You will ask "who will pay for it" and the sad truth is that future generations WILL pay the costs for whatever we do today, but what legacy do we wish to leave our sons and daughters? A legacy of handouts and dole? Of payouts to corrupt officials and incompetent corporations? A legacy of despair? Or would we rather pass on a legacy of HOPE, one that opens frontiers, provides jobs and strengthens the role of science, education and technology in our society?
It is said that all-out war will revitalize a nation's economy (but only if they win) by requiring productivity in manufacturing and technical capability. However, a renewed commitment to Space Exploration will have the same effect - if we let it.

We stand at a crossroads. How about we choose the road that leads to Space?

The GUIDE: Hansen's Disease - The surprising neural basis of leprosy

2012-01-26T14:00:00.001-08:00

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This post is partially a reprise of a blog from last spring written to coincide to my visit to the former leper colony on the island of Molokai. It is reposted today in the context of "Neural Diseases and Disorders as Plot Devices" due to prior use in Science Fiction / Fantasy (The Chronicles of Thomas Covenant).

Leprosy – Hansen's Disease – is an infection by Mycobacterium leprae and/or Mycobacterium lepromatosis. Despite the usual misconception, leprosy is not primarily a skin disease, nor does it result in "limbs falling off" as popular belief would have it. Leprosy is primarily a disease of the nervous system. The mycobacterium damages the sensory nerves of the periphery that lie close under the skin, first affecting tactile sense, then the fibers that transmit pain. The pale, blotchy skin lesions that have been the hallmark of leprosy from ancient times, appear as the "dermatomes" of the skin lose their neuron connections.

Dermatomes are regions of the skin that are served by a common source of "afferent" nerves ascending to the spinal and brain, and "efferent" nerves returning to the skin. Severing a single nerve will result in loss of sensation in a patch of skin from <1 to >10 cm square, depending on location on the body. Dermatomes on the fingertips are quite small, reflecting the many densely packed nerve endings that provide fine touch and sensitivity. Dermatomes over the ribs, hips and thighs are quite large, since tactile sense in those regions does not need to be as precise. Hence dermatomes are a necessary feature of the brain being able to localize *where* a sensation is coming from.

With the most common form of Hansen's Disease, the loss of sensation occurs first, and the skin lesions appear later as the dermatome loses all neural connections. A rarer variety exhibits the pale lesions, raised patches, nodules and bumps, with the numbness and sensory loss occurring much later. Ironically, the loss of neuron is due to the body's own immune system, much the same as other neuron diseases such as myasthenia gravis, multiple sclerosis (MS) and amyotropic lateral sclerosis (ALS – Lou Gehrig's Disease). Mycobacteria infect the neurons and change the outer membrane. Immune cells recognize the neurons as infected and damaged and "remove" them, resulting in the loss of neural connections between skin and brain. As more neural connections are lost, they also include the neurons returning from brain to the skin that regulate blood flow, perspiration, and other factors, resulting in the lesions normally associated with the disease.

In advanced stages, the mycobacterium attacks the cartilage and tissue around the joints, eventually damaging the bone. The resulting shortening of bones and joints in the hand and feet gives the appearance of loss of the digits even though amputation would only occur if the digit was gangrenous. The very severe, nonhealing lesions as well as loss of limbs results not from the disease itself, but from untreated infections that are (A) undetected due to lack of pain, and (B) impaired healing due to loss of neural control of blood and lymph flow. Untreated secondary infections can result in gangrene which in turn requires amputation; thus any limbs lost to leprosy usually result from factors other than the disease itself.

We now know that leprosy is *not* very contagious. The amount of contact required to be infected is usually only encountered by family members or caregivers. It is likely *not* transferred via the skin or by the lesions, but by nasal secretions and mucus, much the same as influenza. There appears to be a genetic susceptibility, resulting in the disease occurring within families (as well as due to the close, repeated contact) and we now also now that >95% of humans are naturally immune.

Contrary to the Ancient Greeks who first described what we know as Hansen's disease, it is not about being "unclean." Instead, it is all about the neurons, but then, isn't everything?

The GUIDE: Migraine triggers

2012-01-24T14:00:00.000-08:00

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Since writing my Migraines posts, I have been asked about triggers for migraines.

Many of you should be aware that migraine sufferers report many different types of triggers for their symptoms. The most common headache triggers - eyestrain, polluted/stale/contaminated air, stress, disrupted sleep cycle - can also trigger migraines, but there are some very specific food and environmental triggers as well.

The food triggers - artificial coloring agents, cured/preserved meats, sausage, pepperoni, yeast breads, pizza, cheeses, caffeine, etc. can be found at WebMD (http://www.webmd.com/migraines-headaches/guide/triggers-specific-foods) which is a good start for migraine information.Understanding *why* there are specific triggers to migraines involves going back to the mechanism of what a migraine is - a reaction of the blood vessels in the brain - and the feedback loop of serotonin and histamine release that both result from and promote the vascular "spasm."

Foods such as peanuts, sourdough, yeast breads, certain fruits... can trigger food allergies. Even non-obvious allergies such as mold and mildew allergy can be triggered by yeast - thus resulting in increased histamine levels in the blood, triggering the vascular reaction in sensitized blood vessels in the brain.

Preserved, cured meats contain nitrates. In particular when those meats are fried or grilled (bacon, sausage, steak), nitrites and nitrosamines are produced, and those chemicals are also known to irritate sensitized blood vessels. In addition, nitrosamines are metabolized by some of the same pathways as serotonin, and can lead to increased serotonin levels.

Many "stinky" or aged cheeses contain tyramine: Bleu cheese, brie, aged cheddar, stilton, feta, gorgonzola, mozzarella, parmesan, muenster, swiss - the list goes on, and tyramine is also found in processed meats, fava/garbanzo/lima/pinto beans, avocados, raisins and fruit. Tyramine is one of the chemicals in the pathway by which serotonin (chemical name 5-hydroxy-tryptamine) is made and broken down. Tyramine containing foods boost the serotonin levels in the blood.

Monosodium glutamate, caffeine and aspartame (containing phenylalanine and aspartate), as well as similar chemicals, contain components of common neurotransmitter chemicals. They can cause abnormal dilation or irritate the blood vessels as well as interact with normal brain function when levels are too high. On the other hand, if a person is used to high dietary levels, headache and migraine can occur from abstinence or lack of those chemicals: A person who consumes 5 cups of coffee a day during the week may suffer caffeine-withdrawal headaches on the weekend.

Other environmental contaminants such as pollution, perfume, typically interact with allergy and histamine reactions of the immune system. Chemicals such as histamine, nitrates, alcohol, and some of the neurotransmitters which dilate blood vessels are positive reinforcers of the vascular reaction that promotes a headache/migraine. The lack of chemicals such as glutamate, aspartate, caffeine, that constrict blood vessels leads to a "rebound" dilation which acts the same ways. Understanding that histamine and serotonin are the primary chemicals involved, and any food or reaction that increases histamine and serotonin levels will go a long way to understanding and controlling migraines.

For food triggers, doctors recommend trying an "elimination diet" - go to WebMD or MyChronicMigraine for lists of foods - eliminate them *all* from your diet for 2-4 weeks, then gradually add one food from the list back into your diet each week. If migraines stop or are reduced with all trigger foods eliminated, then a trigger food is like a culprit. If migraines return after a particular food is restored, it is likely a trigger (but not the only one), remove it for a week, then resume by adding back in other foods until you have identified the one or more foods that trigger your migraines.

Keep a food and migraine diary. It is extremely important and will help you and your doctor identify your trigger foods.

Until next time - feed your brain... the right foods!

REVIEW: Three for One - Extraction Point and The Case of the Displaced Detective (The Arrival and At Speed)

2012-01-22T14:00:00.000-08:00

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The very first blog on this site was a book review, but I really haven't done any since. Since so much of what is write is about the Science in Science Fiction - or Scientists Writing Fiction, I just had to write about this trio of books by scientist-authors.

Travis S. Taylor, Ph.D. is a rock-star of science, with multiple degrees in the physics, optics, aeronautical engineering, etc. When John Ringo created the character of William Weaver in his novel "Through the Looking Glass," he was criticized for the unbelievability of a scientist/mountain biker/martial artist/musician/reluctant soldier. John's counter was that the only difference between the fictional character and real-life role-model "Doc Travis" was that Taylor was more familiar with firearms than his fictional counterpart."Doc" is all that, and more, a scientist, writer, and lead guitarist/singer for a rock band - a literal "rock-star" of the SF world.

Stephanie Osborn is also "all that" - a former NASA payload flight controller, copy, teacher, ordained minister, college instructor, and writer. Again, with multiple degrees in astronomy, physics etc., Steph would be the sort of character that would raise an eyebrow if you didn't actually know this bright, accomplished woman. Taylor and Osborn have teamed up to bring us a wild-ride novel in Extraction Point, a mystery-adventure with a strong science background.

Dr. Reagan "Ray" Brady works for a clandestine agency that investigates mysterious occurrences. Dr. Brady, and team - including his wife Samantha (incidentally, the leader of the investigation team), are investigating a series of crimes in which the perpetrator manages to get into and out of locked, secure places with no trace of forced entry or exit. Further evidence has linked the same person with events that affect the advancement of science over a 300-year period. The team begins to wonder if they are tracking a "Santa Claus" - a alien - or an "Easter Bunny" - a time-traveler; and come to the reluctant conclusion that their mysterious opponent is a "Santa Bunny" - an alien from a different time.

Along the way, the reader is treated to some real multidimensional physics, and string / membrane / quantum theory intermixed with plenty of action and a fantastic adventure. The writing is seamless and well-matched. In fact, I spoke with Stephanie Osborn about the book and tried to guess which sections she wrote, vs. those written by Taylor. I got it wrong - it is truly difficult to tell which of the authors wrote which section! For those who may accuse the authors of writing "Mary Sue / Marty Stu" adventures (writing thinly veiled chacterizations of themselves in heroic context) I would point back to the bios of the authors above. Is it still a "Mary Sue" when the descriptions are real? I for one welcome the depiction of scientists as heroes.

This is a book with both science - real, accurate science! - and adventure. I finished the book in two sittings and gave up a fair bit of sleep in the process. Extraction Point is available in paperback print-on-demand and eBook media from Twilight Times Books. Here's a link to the listing at Amazon's Kindle store, the eBook is a great bargain.

To continue with this trio of Science fiction fun, we turn to Stephanie Osborn's solo offerings: The Case of the Displaced Detective: The Arrival, and its close-on-the-heels sequel The Case of the Displaced Detective: At Speed. In these introductory books to a series (my understanding is that Steph is on Book 5 already) Dr. Skye Chadwick has found a way to view other realities through Project Tesseract, forming a hyperspace "windows" to worlds not too unlike our own - but with a few key differences. Long a fan of Sherlock Holmes mysteries, Dr. Chadwick has discovered a world in which Holmes was a real, historical character, and not a product of Sir Arthur Conan Doyle's imagination. While never explicitly stated, Project Tesseract is able to view across time, as well as hyperspace, thus Dr. Chadwick and team have chosen for their first full test to view the tragic battle of Homes and his enemy Prof. Moriarity at Reichenbach Falls, Sweden. However, Chadwick, a former reserve police officer cannot passively observe, but attempts to intervene, saving Holmes' life and inadvertently bringing him through the Tesseract into Chadwick's home dimension and time.

Book One - The Arrival - is a great exploration of "what-if" with Sherlock Holmes introduced to the Twenty-first Century. Mixed in with the high-energy physics and hyperspace theory is a mystery worthy of Holmes, finding a spy ring on a secured military installation, detecting and preventing sabotage and updating the Victorian detective's skills. Book Two continues the mystery, builds the relationship between Holmes and Chadwick, and explores the personality that yielded the greatest detective of (fictional) history.

Again, these are great reads, and I finished the first volume, screaming for more. Fortunately for me, Book Two was readily available. I think it took me 5 days to finish, but only because my schedule was interrupted! Two particular scenes come to memory - in the first, Osborn's history with NASA comes through as the Project Tesseract team answers a Go-NoGo checklist in a Mission Control moment familiar to fans of "Apollo 13" and "From the Earth to the Moon." In the second scene I started laughing because I saw so much of the author's background in the story - then had to explain myself to the person sitting next to me on an airplane.

These are enjoyable books and I am eagerly awaiting the forthcoming volumes. Osborn is very respectful of the Holmes canon, and has created a believable characterization for Holmes in the modern world. This link is to the Amazon Kindle listing for Book One. I highly recommend it!

Stay tuned for more of The Lab Rats' Guide to the Brain, science news and SF book reviews!

The GUIDE: The "A's" have it...

2012-01-20T14:00:00.000-08:00

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I have, on many occasions, railed against "stupid movie science" in the form of getting brain science wrong, or being unimaginative regarding use of brain disorders. As I have often said, the most misused brain disorder in TV (especially soap opera), movies and books is amnesia. Today's blog is meant to introduce the reader (and writer) to a number of other "Axxxx" diseases that can be used with interesting consequences in fiction.

Amnesia: Total amnesia of the sort depicted in the typical Soap-Opera head-injury scenario is rare. Even rarer still is the fiction construct of a person living a totally different life for decades, then receiving another head injury and reverting to their original life and memories! However, amnesia does occur, particularly with trauma or head injury, and it often encompasses about 2-3 hours before the incident, and about 1-2 days after. The "retrograde" amnesia (forgetting past memory) is due to the fact that the normal processing of short-term to long-term memory is disrupted by injury. The "anterograde" amnesia (inability to make new memory) is a result of swelling or infection cause pressure on the hippocampus. With increased pressure comes decreased blood flow and decreased function. Once the swelling goes down, the normal processes of encoding and storing memory can continue. However, there *are* cases of surgery (deliberate or accidental), head trauma and disease that cause damage to hippocampus and produce a permanent anterograde amnesia. I discussed such a classic case of amnesia in the epilepsy blogs last year.

Agnosia: A special case of amnesia, agnosia results from very localized damage to the brain. In particular, the damage occurs to the association areas of the brain that process the basic sensory information and deliver it tot he parts of the brain that make decisions and control our actions. In the visual areas, agnosia manifests as "visual neglect" the subject ignores what is in one part of the visual field, even though the eyes and pupils react to stimulation of that part of the field, and there is evidence that *some* of the sensory information is getting through to other parts of the visual system: for example, the eyes can track a moving object through that field, and the a subject shown an embarrassing picture to that part of the field will blush and act embarrassed without being able to say why. Neglect can apply to the body as well, a patient may not be physically aware of sensation from a limb or part of the body, even though the spinal cord, motor control, reflexes and pain reactions are intact. Frequently the damage is to the thalamus, which relays sensory information through the brain, or to specific nerve tracts in the Parietal Lobe.

Ataxia: Often confused with simple clumsiness, ataxia is a failure of the brain to provide coordination to movement. Ataxia may be accompanied by tremor, rigidity or weakness, and is thus hard to diagnose differently than other diseases. However, the key finding is the inability to coordinate the movement of more than one arm or leg at a time, clumsiness that occurs when a person stops concentrating on the movement, or the inability to stop a movement once it is started. Ataxia usually results from damage to the cerebellum, but may also be caused by damage to deep brain nuclei or brainstem.

Apraxia: Like ataxia, apraxia results in a failure to get the body to do what the patients wills it to do. In a typical case, it is easy for a patient to bend down, pick up a baseball that is in their way, and toss it away. However, if the patient is told to pick up the ball, or verbally expresses the desire to throw the ball, they cannot do it. All of the motor and sensory abilities - including coordination - are intact, but the patient cannot turn intent into action. Damage to the premotor areas of Frontal Lobe or the associational areas of Parietal Lobe are usually involved. Neither the motor nor sensory cortex areas are damaged, though, and all abilities remain intact.

Aphasia: When apraxia occurs within the speech centers, it is termed "aphasia." We all experience minor bouts of aphasia that occur as "tip of the tongue" phenomenon, but these are usually due to the inability to perform the appropriate memory recall of a word. Aphasia is different, because a patient can hear the word, write the word, choose it out of a list, but cannot speak it. It is a specific disorder of Broca's area, which sends signals to the motor cortex for diaphragm, throat, tongue and mouth to form words. Broca's Area is in the Frontal Lobe, just below and forward of the motor cortical areas for the face and neck, and lying just over a bundle of nerve axons (the arcuate fascilus) that run from sensory association areas of the Parietal Lobe, underneath Wernicke's Area (language), Broca's Area, and terminate in the "cognition" ares of the Frontal Lobe. Aphasia is frequently caused by damage to Broca's Area or the arcuate fasiculus.

Alexia: Also known as visual aphasia, this is a failure of language and speech generation - in this case the failure to recognize and understand words. Alexia is usually visual, and shows as the inability to recognize that printed or written characters represent language, i.e. "word-blindness." There are auditory forms, but those are usually associated with obvious hearing disorders. If the person retains the ability to speak and write words, then they have alexia without agraphia and the damage is between the visual cortex and Wernicke's area and confined to the lateral Parietal Lobe. Damage to Wernicke's Area also causes loss of ability to write and speak coherent language. Note the similarity to "dyslexia" and you can see how important the Wernicke/arcuate fasciculus/Broca linkage is to transforming sensory input to language.

So there, five new "A-words" to add to amnesia and spice up the plot of that new novel or movie. The unfortunate thing, though, is that these disorders are not new, and doctors face them every day with stroke, head trauma and battlefield trauma patients. Then again, the best stories come from real life incidents.

Thanks for reading, and tune in next time for some book reviews and a refresher on brain basics for The Lab Rats' Guide to the Brain!

The GUIDE: "How does the aspirin know where my pain is?"

2012-01-18T23:59:00.000-08:00

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In yesterday's discussion of headache, I deliberately left out the discussion of common pain medication for headache. If the headache is just that - a short-term disturbance of blood flow that causes an indefinite "ache" of the head, then "common" medicine is usually the best treatment.

Certainly there are rapid treatments available in the lab or hospital setting - breathing oxygen is a rapid way to cause the blood vessels in the brain to constrict, stopping the feedback loop of irritation, blood vessel dilation, inflammation and further irritation that causes the headache. For severe cases, you need to block the serotonin and histamine release, and in very severe cases, there are other neurotransmitters and chemicals that need to be blocked...

... but headache and common body aches and pains have one feature in common, and one common treatment. The common feature is inflammation, and the common treatment is aspirin or other Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). Damage or stress to cells of the body - whether muscles or blood vessels - results in the release of cytokines - chemical agents that act on other cells. The common feature of cytokines is that they tend to "irritate" other cells in the body. The body reacts by causing inflammation - swelling, increased fluid in the tissue, increased blood flow, and an increase in the immune cells entering the area. One of the key inflammatory chemicals is arachidonic acid. Through the pathway at the right (figure by JFD Wolff, via Wikimedia Commons), Arachidonic acid is converted to various compounds called prostaglandins and thromboxanes. PGE2 is one of the critical agents that causes and prolongs inflammation.

The stage indicated "PGH2 synthase" is more commonly called "cylcooxygenase" or COX and there are COX-1 and COX-2 inihibitors for the two different forms of COX enzyme present. Aspirin - acetylsalicylic acid - inhibits both COX-1 and COX-2, as do most of the NSAIDs: acetaminophen/paracetamol (Tylenol), ibuprofen (Advil), naproxen (Aleve), etc. There are selective COX-2 inihibtors that appeared even more effective, since that COX-1 is less involved in inflammation, but the risk of cardiac side effects has removed them from the market.

So, the aspirin doesn't need to know where the pain is, it just needs to block this one reaction that is present wherever pain occurs. Overall, NSAIDs are the most effective relief of inflammation-related pain that we have - and it (aspirin) all started as willow tree bark.

See you next time!

Stop SOPA & PIPA

2012-01-18T08:04:00.000-08:00

Graphic borrowed with permission (the APPROPRIATE way to handle internet content) from Howard Taylor's Schlock Mercenary website.

Since I post science information that is supplemented from material found online, anyone with an accusation of copyright infringement could have my site blocked and all content removed - even though I've sent over a year writing my book! There is no protection of free speech, no due process and no recourse in SOPA/PIPA. It may be defeated by the Supreme Court, but the process will take years and too much damage could result. Better to never let it get out of Congress.

Please join in telling the U.S. Congress not to pass the SOPA and PIPA bills.

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The GUIDE: Migraine

2012-01-17T14:00:00.000-08:00

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Oh. The PAIN!

Headaches occur at a minimum of once per week in persons living in industrialized society. They can be simply a slight pain induced by too much reading, polluted (or stale) air, food triggers, not enough sleep or allergic reaction. It is tempting to refer to all severe headaches as "Migraines", especially if they occur with regularity. However, not all headaches are migraines, and not all migraines are the same.

Let's start with some definitions and descriptions. First, headaches are really neural in that they don't mean that the cells of the brain are acting in any manner different from normal. Instead, headaches are a vascular problem. Metabolic imbalances cause tiny blood vessels to expand, the increased blood flow causes changes in other blood vessels and in brain activity. In addition, there is release of the neurotransmitter serotonin, and its close chemical sibling: histamine. Those chemicals cause further reaction of the blood vessels, leading to the sensations we know as a headache.

The involvement of histamine means that there are many ways of triggering headaches - sinus congestion, allergy, food reactions, excess carbon dioxide in the atmosphere, etc. The CO2 involvement is one reason why breathing oxygen relieves headaches - high CO2 causes blood vessels to dilate (get larger) increasing blood flow in the brain to higher than normal levels, while high O2, low CO2 causes those same vessels to constrict and reduce blood flow to normal levels.

All of these causative factors lead to the same sensation: discomfort and perceived pressure in the forehead area, behind the eyes. The brain itself does not have the nerve endings that signal pain in the rest of the body, so the sensation of pain is really one of pressure, and it results from the "cognitive" areas of the brain trying to find a way to represent the chemical changes that result from the unusual blood flow patterns.

Migraine starts the same way, but adds a new components, because migraines really do involve a change in the electrical activity of the brain. To start with, the majority of migraine sufferers report a "prodrome" or "aura" before the pain sets in. This aura is quite frequently associated with visual changes - light sensitivity, flashing, pulsing, tunnel vision, blurring, spots or even temporary blindness. In this manner, the aura of a migraine is quite similar to that preceding an epileptic seizure (see prior blogs on Seizures and Epilepsy), but is most often visual and does not spread or involve other senses. The aura signals the initial "irritation" of the blood vessels that supply the brain, but the migraine pain itself comes from the later reaction in which neuron activity is suppressed by what is called "spreading cortical depression." No, this doesn't mean depression in the clinical sense, but that brain activity is in fact suppressed and only the strongest (and most noticeable) signals can be processed. The video above illustrates the spreading depression in the orange band that starts in the visual cortex and spreads up and forward to include the Parietal, and even the Frontal Lobes of the brain.

The interesting parallels between migraine and seizure continue, but migraines are not epileptic in nature. Seizures do involve some element of cortical depression, reduction in normal brain activity is necessary to set up the abnormal synchronous activity of an epileptic seizure. After the seizure passes, there can be spreading cortical depression. However, the synchronous activity does not occur in migraine, only the spreading depression, and that appears to result from the serotonin and histamine release from the cells lining the blood vessels. Still, some seizure medicines (sumatriptan - Imitrex) can be useful in treating migraines in that they can limit the spreading cortical depression by altering neural response to serotonin. Preventative medication for migraines often involves blood pressure/calcium blocker medicines such as Verapamil that can reduce the "irritation" of blood vessels. Injection of very small amounts of botulinum toxin (Botox) into the blood vessels that most frequently react to induction of a migraine can also reduce the "irritability" and reduce the frequency of migraines.

Migraines typically last from 4-72 hours and are accompanied by extreme light sensitivity, nausea, blurred vision, fatigue, hypersensitivity to sound and yes - short-term psychological depression. However, it is very easy to call any severe headache a "migraine" even when that is not the case. Allergic rhinitis - i.e. a "stuffy nose" and sinus congestion can trigger headaches that react to pressure in the sinus cavities that surround the nose and sit adjacent to the olfactory bulb - the "smell" center of the brain. The proximity of sinus to the Frontal Lobe means the pressure gets translated to the brain, and the neurons react with activity that signals pain.

And yet, migraines may very well have an allergic component. A well-known trigger for migraine is certain foods and food additives. Nitrites in cooked/preserved meats, artificial coloring agents, phenylalanine in artificial sweetener, food allergens such as tomato or nuts, and surprisingly - yeast breads. The reason is because any trace of food allergy (or mold allergy, in the case of yeast) can cause the histamine increase leading to migraine.

I did mention, though, that not all "migraines" are in fact the classic migraine described here. "Cluster headaches" - so named because the headaches occur in "clusters" that frequently occur at the same time each day, with pain in the same area of face and/or head, and occur for weeks or even months at a time - vary from migraines and conventional headaches because it appears that they *do* involve some unusual brain cell activity. Cluster headaches are not preceded by auras, and the pain is quite often confined to one side of the face and head. They are still treated with some of the same drugs as headaches and migraines, as well as a few specific drugs to disrupt the activity of the neurons that trigger the headache. If these treatment options fail, the docs need to take a look inside the head - not to see if there is anything missing, but to look for unusual blood vessel formation or something that might be causing pressure.

Headache is all about blood pressure and blood flow, since this Guide is all about brain disorders at plot devices, it is important to consider what could cause headaches and migraines to stop or start - and that comes down to anything that disrupts blood flow. Physical head injury, hormonal changes (puberty, pregnancy, menopause), blood loss, allergy, surgery - all of these could trigger the onset, or mark the cessation of a lifetime of headaches. Don't forget the debilitating effects - imagine if during his Labours, Hercules had needed go lie down for 3 days to allow a migraine to pass! Then again, a headache-ridden Theseus may have welcomed the dark and dank Labyrinth and slain the minotaur if only for access to a refuge from sun and sea!

Tomorrow, to complement this blog will be a short article on pain medication. Thanks for reading!

- s2la

NEWS: The Return

2012-01-16T10:02:00.000-08:00

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OK, I've been slacking long enough. The previous six months have seen a flurry of activity in the day job, including grant proposal *re*-submissions, scientific manuscripts sent in, revised, edited, and revised again, plus three major scientific meeting presentations, a bunch of family trips and one SF convention.

So it's a new year and we need to get this show on the road again - literally - I will be participating in Stellarcon, DeepSouthCon50, LibertyCon and Dragon*Con this year, with a possible on RavenCon. I'm taking my appeal for accuracy of Science in Science Fiction to the cons and am pleased to participate in any serious or humorous panels that draw on scientific knowledge and background.

Put simply, SF cons are *FUN* and I enjoy them. If you are attending any of these cons, drop by the panels or the Bar Fly Central (Baen's Barflies) and say hi!

So, for a reintroduction to this blog, I highly suggest clicking on the Tab above: "What is the Lab Rats' Guide to the Brain" which is a "sticky" post that combines many aspects of my prior posts "Back to Basics" and "Brain and Brain, what is Brain?"

My plan for this reboot is to start with today's introduction, jump right back to our discussion of brain disorders with the next several posts on Migraines, The Flurry of A's (Amnesia, Agnosia, Apraxia, Ataxia and Aphasia) and Hansen's Disease, then catch new readers up with a reprise of Brain and Brain and Back to Basics.

---

*For Baen's Bar followers, I am posting this to "Baen's Bar" conference to let you know that the blog is back. Regular mirroring of the blog will still occur in "Sarah's Diner" conference as before.

Happy HOLYdays!

2011-12-23T17:31:00.000-08:00

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Well, folks, it's been a bit rough trying to keep up this fall. Frankly, I couldn't.

I've been working on resuming the final sections of The Lab Rats' Guide to the Brain and will be back in the new year with new content.

I'm also going to do a bit more commentary on Science in the news, as well as SF/F convention reports on panels and topics of scientific interest. The posting schedule may not get back to a daily or even every-other-day schedule... yet... but I will try to have several blogs of new content up each week.

Thanks for hanging in there with me this fall and I hope to see you all in the New Year.

In the spirit of the season, Merry Christmas, Happy Hanukkah, Joyous Solstice, etc. - in other words, Happy Holydays and best wishes to all!

Poking fun at myself...

2011-12-22T22:03:00.000-08:00

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There is a bit of fun going around internet and Facebook this week, regarding how a noted Science Fiction author might order pizza. [http://boards.straightdope.com/sdmb/showthread.php?t=635193 for the link impaired.]

As I write to educate about the brain, and particularly how to incorporate brain science in SF, I also read about the skills that writers must develop. A particular weakness of beginning writers is the tendency to "infodump" and put too much background information into the writing (often in the opening of the novel.)

David Weber is a master at the "As you know, Bob..." method of inserting small background descriptions into his stories, hence the humor in the above link.

Another board has been playing around with the idea, poking fun at SF authros and their writing styles. If I can get permission, I will post links as they go up. One that I created for Novelist Stephanie Osborn is here. [http://www.sff.net/people/steph-osborn/AlienChangeling.html] (To understand the humor in the post, it helps to know that Steph was a NASA payload specialist and spent many shifts in Mission Control. The style and lingo sneak out in her books.]

Then it occurred to me that I might be setting myself up to be parodied in the manner.

Well, far be it from me to resist, in fact, I'll do it myself. So sit back, have a breadstick, and read:

How Speaker to Lab Animals orders pizza...

"First let's look at how speech patterns are generated. Just as important as Broca's area in the left frontal lobe of the brain is Wernicke's area which is located at the junction of the temporal and parietal lobes - in fact it is directly in the path of projections from hearing and vision centers, which is logical since Wernicke's area mainly processes language that we see and hear. The proximity to the temporal lobe memory processing regions is also important since the brain must match sight and sound against memory to determine what is real language vs. nonsense syllables...

"... vocal processing involves many different muscular systems. The actual pitch and tone of speech comes from loosening or tightening neck muscles. The 'vagus nerve' (also known as Tenth Cranial Nerve) controls the throat or internal muscles, while the 'accessory nerve' (Eleventh Cranial) controls external neck muscles. The tongue is controlled by a complex of nerves including the 'glossopharyngeal' (Ninth Cranial), vagus, and 'hypoglossal' (Twelfth Cranial) nerves...

"...thus the mechanism for mouth movements is directly controlled by cranial nerves and does not require much of the spinal cord and conventional motor cortex. This is one reason why 'locked-in' quadriplegic patients learn to use neck, tongue and facial muscles for control of wheelchair and computer. Of course, speech still requires enough airflow to cause the vocal cords to vibrate. Without sufficient spinal cord activity to take a deep breath and let it out slowly, it is not possible to speak...

"...Broca's area is the brain region most associated with speech, and as with many of the specialized brain processing areas, is closely located next to the face and neck areas of the motor cortex. In addition, it sits directly over the arcuate fasciculus, a subsurface bundle of nerve projections from the sensory association areas (including Wernicke's area) to the frontal cortex...

"Extra-large original crust. Extra pepperoni, extra cheese.

"No breadsticks."

(pause)

"Thirty-five minutes? Thanks."

(click)

"The sense of time passing is intriguing, for while there is no specific 'timer' in the brain such as in computers, there are many oscillatory rhythms which may fulfill a similar function..."

This just in... again...

2011-12-21T07:30:00.000-08:00

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So, this week, media reports once again discovered the influenza virus research by the Erasmus Medical Centre in Rotterdam that I commented on here. Note that this research was originally reported at a scientific meeting in September of this year, so it isn't really urgent, breaking news. What is news is that the U.S. Government is asking the journal Nature to censor the research report.

Once again I have been asked a number of questions about the ethics and the practicalities of the work. The language of those condemning the research and public release of the information usually protrays the scientists as "educated idiots" and "dolts" to meddle in something as dangerous as influenza.

Such vitriol does a great disservice to the scientists, hence my vigorous defense of the field.

So, here is a brief mailbag entry from Nate:

S2LA,

Not saying the research should not have been done, just have issues with theapparent handling of it.

Do these universities have the needed controls and security to protectagainst accidental release? I know that here in the States the physicalsecurity varies incredibly.

What level of sophistication would be needed to do this type of forcedmutations? Is it something that can be fired up in a community college levellaboratory or a midsized state U or would it take a specialized research lab?

Is it something like nuclear weapons and most other technology? If you knowit is possible to do it is much easier to reproduce?

What are the steps from where they are at to get to a useful vaccine?

Thanks, Nate

Verygood questions, Nate, so let's look at them step by step:

Likelihoodof release:

Ifthis is a viral research lab, it really doesn't matter which country the lab isin, they have to take precautions to not infect themselves, so there really isno difference between the lab in Rotterdam and one at say, Emory orStanford. It's probably a level 3 biocontainment lab. There *is* adifference between that and a CDC Level 4 or 5 lab but still, the chances ofrelease are low.

So,what if it *is* released – one to 5 people in a typical lab would be exposed tothe virus – however, what form is it in? To infect a human, H5N1 has to enterthe lungs in aerosolized form. What that means is that the virus needs tobe in small fluid droplets with a certain amount of live or newly dead animaltissue in the droplets to keep the virus alive. Sanitary precautions suchas alcohol sanitizer and wipes, disinfectant containing bleach or iodine wouldkill it. Then there is the fact that one virus particle alone is notenough to infect a healthy human, nor is one human enough to start an epidemicor pandemic. Accidental release is unlikely to start a pandemic (althoughdeliberate release might – so we'll discuss that later) it *may* result in afew people getting sick.

How bad is this flu?

From TheIndependent's story: "The fear is that if you createsomething this deadly and it goes into a global pandemic, the mortality andcost to the world could be massive," a senior scientific adviser to the USGovernment told The Independent, speaking on condition of anonymity.
"Theworst-case scenario here is worse than anything you can imagine."

This isfear-mongering, pure and simple. No one talked to a physician about howthe flu is spread, no one talked to a scientist. They sat around and said"OH WOW, We think this is BAD" and published it. I am soabsolutely livid about this sort of thing that it is hard to type the response.

It is true that theH5N1 influenza has had a mortaility rate of about 60%, but there have beenabout 500 cases worldwide – EVER! Only 500. All of those cases weretransmitted from chickens to humans, so the humans did *not* contract a human influenza,they contracted the actual avian version of the virus. This virus infectsthe lower respiratory tract – the lungs – and causes pneumonia. Thepersons who died, did so from pneumonia, not the flu itself.

But what abouthuman transmission? To answer this, I have to lecture a bit on how virustransmission works. First, a human has to come in contact with the viruscontained in a medium in which the virus will grow. Viruses are notalive, they can't be grown in petri dishes or a test tube – at least notwithout living cells. Viruses enter living cells, than take over thenormal cell growth and replication mechanism by inserting their DNA/RNA inplace of the cells' own. The cell is forced to make new copies of theviruses, which then rupture the cell and spread. Without cell material, avirus is inert. When the environment dries out, many viruses becomeincapable of infecting cells. Treatment with heat, soap, iodine, bleach,ammonia, etc. will break down the protein coat of a virus making it"dead."

SO a virus has tobe *in* a cell in order to make copies to infect more cells. Note thatmutations in the virus are likely to occur with each new type of cell entered –but more on that later.

Spreading the influenza virus:

Following the fateof one "golden virus" particle in Patient Zero (P0): P0 handlespoultry in Thailand, he beheads, cleans and plucks hundreds of chickens aday. One chicken is infected with H5N1. On beheading, the bloodsprays everywhere forming a spatter and mist, some of which lands on P0's face,and some is breathed into his lungs. Unlike H1N1, the virus landing innose and mouth does not cause infection, however the mist is breathed deep intothe lungs. The ciliated cells of the nasal (nose) and pharyngeal (throat)mucosa do a pretty good job of catching and filtering out the aerosoldroplets. So do the ciliated cells of the trachea (airway) –unless P0 is a smoker, since nicotine paralyzes cilia.

Nevertheless,99.99% of the droplets are caught before entering the lower lungs. H5N1enters cells in the alveoli (air sacs) of the lungs. One virus entering aweaker cell can produce between 100 and 1000 copies of itself. Once thecell fills with virus particles, it dies, ruptures, and releases thevirus. However, not all cells are susceptible to entry by thevirus. Macrophages (immune cells) in the blood, lymph and lung tissueconsume dead and dying cells, and the virus may not get a chance tospread.

With repeated lowexposure, P0 develops antibodies to the virus and it never gets a chance tospread, but let's suppose P0 gets a large virus exposure and has low resistanceto viral infection. More lung cells are infected, rupture, and the lungsstart to inflame and fill with fluid. This takes about 5-7 days. Once there is fluid build-up, P0 starts to cough. Now he is infectious toothers, because when he coughs, he sprays a mist of fluid, dead and dying cellsand virus into his environment. Note that with a "dry cough"(smoker's cough, asthma or emphysema) there is little to no moisture to supportthe virus. With a "wet cough" (bronchitis, allergy andpneumonia) the fluid in the airway sprays out with each cough.

A person breathingin the aerosol from P0's cough (5-7 days after his infection) can catch H5N1,right? Um, no. Not so far. Once again, viruses tend to mutatewhen they enter new types of cells. The avian influenza virus mostly hasits effect by causing pneumonia – swelling and fluid accumulation in theextremely nutrient, oxygen and fluid-rich environment of the lungs. It hasmutated, and the version sprayed out in each cough does *not* have the abilityto survive in dry air or infect other humans.

Yes, P0 has a 60%chance of dying of pneumonia, as of one year ago, there were 510 reported H5N1infections and 303 deaths, but no proven, ubiquitous human-to-humantransmission.

Again, from TheIndependent: "For the first time the researchers have beenable to mutate the H5N1 strain of avian influenza so that it can be transmittedeasily through the air in coughs and sneezes. Until now, it was thought thatH5N1 bird flu could only be transmitted between humans via very close physicalcontact."

Researchers inRotterdam made five point mutations to the H5N1 virus that *PRESUMABLY* make itsusceptible to human-to-human transmission. They don't know it for fact,it wasn't tested on humans, so it is not completely proven.s, P0 has a 60%chance of dying of pneumonia, as of one year ago, there were 510 reported H5N1infections and 303 deaths, but no proven, ubiquitous human-to-humantransmission.

TheIndependent: Dutch scientists carried out the controversialresearch to discover how easy it was to genetically mutate H5N1 into a highlyinfectious "airborne" strain of human flu. They believe that theknowledge gained will be vital for the development of new vaccines and drugs.

Thediscovery has prompted fears within the US Government that the knowledge willfall into the hands of terrorists wanting to use it as a bio-weapon of massdestruction. Some scientists are questioning whether the research should everhave been undertaken in a university laboratory, instead of at a militaryfacility.

What does it take to perform the forced mutations?

OK,now we get back to Nathan's question about what it takes to do this sort ofmutation and virology, can it be done at community college level? Or doesit take a specialized lab. Offhand I would say that this sort of workrequires a dedicated virology lab. First, you need knowledge of culturingviruses, it's not easy, but can be readily learned. Performing the actualmutations, though, requires gene sequencing equipment and a means to ensurethat the appropriate sequences are maintained in the virus.

Is this like making nukes? Once you know it is possible, it's easy to reproduce?

No,Johnny Jihadi is *NOT* going to be doing this in his bathtub. The truth is thatany lab *capable* of doing the mutations probably already has the knowledge andability to do so. Has anyone noticed how many med school and grad schoolstudents are foreign nationals? At one point, my department was 1/4Chinese, Indian and Middle Eastern students. Many departments are evenhigher. Does anyone *seriously* think that terrorist organizations andadversarial nations don't recruit highly educated people and supply them withwhat they need?

Themutations are likely very easy to introduce. Why? Because virusesmutate naturally.

Letme say this again: Viruses mutate naturally.

OK,now I'm going to shout it: VIRUSES MUTATE NATURALLY!

TheInfluenza A virus which is the root of the "H" strain viruses ishighly susceptible to mutation. I mentioned this before and promised adiscussion later – every time a virus enters a new host or new type of cell, itmutates. Every year we need a new seasonal flu vaccine due to themutations from the previous year. One natural consequence is that mostinfluenza epidemics burn themselves out because the second, third and fourthgeneration of the same virus has mutated to a *less* virulent form.

Infact, Tom Kratman and I had to work quite a bit to come up with a scenario fora Smallpox virus that would become *more* not *less* virulent forCaliphate. Frankly, being (presumably) human transmissible, the viruscooked up in Rotterdam isn't exactly H5N1 anymore, and we don't really know howit will react in the human population.

Influenzais also contagious at the same time that the patient shows symptoms. Thevery coughs and sneezes that are symptoms of the flu are the transmissionvector, so the flu virus that the first generation patients could possiblycatch from P0 is already mutated.

Oneblogger* wrote the following "Some dopes in a Dutch lab have made thethreat a lot more real. By mutating H5N1 into a more human threat, thesescientists have given would-be bio terrorists something to salivate over. Theysay they did it because it could help them develop more effective vaccines inthe future, but to me this falls into the category of things you just shouldn'tmess with, no matter how pure your intentions." [*Please note, the blogger is an IT security type, not a biologist, although I am not at all certain that should excuse his language.]

OK,so which "Dopes" would the blogger rather have – ones whoperformed the mutations to determine how easily it could happen naturally(which it really can!) and then be able to quickly produce vaccines – or oneswho ignored the issue until Nature, or someone with less benign intentions,does it for them.

IGNORANCE*IS* THE PROBLEM.

Thereal issue in all of this research is that the mutations could very well happennaturally, and virologists have been expecting it since 2003.

The unasked question...

Now,should it be classified? HELL NO!

Yes,once it is known that there are only 5 mutations required, it may become easierfor others to do so. On the flip side, once the knowledge is disseminatedand the articles published, it becomes common knowledge, and much harder tohide illicit virus or biological weapon production. We can also haveready-made stocks of vaccines on hand to shut down a pandemic before itstarts. The true scare is *not* what if a terror lab produces the virus –but what if it occurs naturally?

Butdoes this mean it should be done in a military lab instead of acollege/university? Not necessarily. First, military labs andmilitary funding are for research with military priorities. It is naïveto think that research into weaponization of H5N1 isn't being done, butdeveloping vaccines for civilian populations would not necessarily have as higha priority. Research into influenza mechanisms for the sake of puremedical research is also probably not a high priority for a military lab.

I'mnot going to speak about the pros and cons of "entrusting" H5N1 tomilitary labs, but rather look a bit more objectively at the issues withrestricting such knowledge to closed intellectual compartments. Classified and restricted information requires clearances and specialtreatment. If an H5N1 outbreak occurs due to natural or belligerentcauses, do we *really* want the knowledge of how to deal with it tied upwaiting for bureaucratic clearances?

Itreally boils down to the concept that folks who might have the will to use H5N1as a bioterror weapon either don't have the technology to do so, or if theyhave the skills and technology, they probably have the knowledge of what andhow to do through other sources – as I said, influenza viruses mutate, it'swhat they do, and anyone who studies them knows it.

What are the steps to get a useful vaccine?

Asfar as making a useful vaccine – until we know a hell of a lot more aboutmaking human cells resistant to viruses – the first thing you need is theactual virus... in the form which infects humans.

Inother words, you need the virus produced in the Dutch labs.

Again, thanks to Nate for his insightful questions and the opportunity to answer them here. I am sorry that posting has been so irregular this fall, I will do my best to get back on a more regular schedule with the new year, and remember, you can always ask questions and I see what I can do to give reasonable, science-based answers that y'all can understand!

-Speaker

On Research Ethics

2011-11-28T16:52:00.001-08:00

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I'm going to take a small step away from neuroscience for this post. In a startlingly real case of life (i.e. my day job) imitating art (i.e. my online presence), I was asked about the following article on the exact same day I find myself having to think like a microbiologist/immunologist again at work.

Way back in the dim mists of time... as a Master's student, I studied Biology, with a strong emphasis on Aquatic Biology. However, to pay the bills, I taught labs and graded papers... in Microbiology. It's a skill I picked up in the course of my undergraduate studies in Biology and Chemistry, and it contributes to the fact that I am a rather well-rounded scientist, with background knowledge of Biology, Chemistry, Geology, Physics and Medicine in addition to my primary (doctoral) skills in Physiology, Pharmacology and Neuroscience. Under the circumstances that I like to use this forum for Q&A and discussions of research ethics, I thought it would be a good diversion to address the following headline:

Man-made flu virus with potential to wipe out many millions if it ever escaped is created in research lab

One version of the story that is making its way around the internet is here:

http://tinyurl.com/6p2xa5wThe picture at right is from the Daily Mail article, and purports to show the new virulent H5N1 virus. I can't verify the accuracy of the photo, but I will tell you that it certainly looks like the glycoprotein coat of a virus - note, that this is not the active part of the virus itself, it is only the outer shell. The "infectious" part of a virus is the DNA or RNA on the inside.

H5N1 is bird flu. It has the potential to be every bit as nasty as the Influenza pandemic which killed between 50 and 100 million people between 1918 and 1920. It should be noted that the so-called "Spanish Flu" was the influenza viral strain H1N1 - more recent known as "Swine Flu" which was responsible for the influenza pandemic of 2009. H5N1 is not yet in the dangerous state because it is not easily transferred between individual humans except through exchange of bodily fluids - and even then it is not terribly virulent in what would be termed the F1 or F2 generation.

In the article, however, it is revealed that scientists have mutated the H5N1 virus to a more virulent form that is transmissible, and they did so in 5 relatively easy mutations. There is much discussion about whether scientists should be "allowed" to perform such dangerous research, and even then if it should be published. I was asked what I thought about (A) the dangers of this flu, (B) whether it should be published, and (C) the ethics of this research. This is particularly apt because a few years back, and SF author friend of mine proposed an H5N1 pandemic as part of the plot line of his book, and asked me to consult on the medical science. For the interested, that book is "The Last Centurion" by John Ringo, and it is available in eBook form here: http://www.webscription.net/p-770-the-last-centurion.aspx and in hardcopy from Amazon or Uncle Hugo's SF Bookstore.

So, under the circumstances, how could I refuse?

Dangerous Research Ahead...

In response to the questions about "should scientists do dangerous research?" My answer is a qualified "Yes." The qualification is that I feel appropriate safety should be taken to prevent release. In my work as a neuroscientist, we have to work with many chemicals that the Centers for Disease Control (CDC) have declared as "Select Agents" meaning that these are essentially dangerous chemicals. Note that these are not synthetics, they are plant and animal toxins that are collected, concentrated and purified. Botulism, cholera and typhus are terrible diseases, and the toxins are deadly, but from research into these toxins we know how they work and how to prevent and treat the disease. Puffer fish (fugu) and cone snail toxins are deadly, yet they are also essential pharmacologic tools to the neuroscientist to better understand neuron/brain cell function both in normal and disease states.

Therefore, the danger of the subject of study alone is not sufficient cause to stop or prevent the research. Yes, precautions *must* be taken, yet still - viruses mutate on their own! The likelihood that such a virulent strain of H5N1 could develop on its own is NOT unlikely. When it does, you'd better believe that our doctors and scientists NEED to know how it behaves and how to treat it (as well as preventing the spread).

Publish or (and) Perish!

There is fear that publishing the results of the scientific experiments would provide a "cookbook recipe" to terrorists or even disgruntled citizens to duplicate the result and create a terror weapon. Basically this comes down to "once we know, shouldn't we keep it a secret?" To this, I say "No," once we have the information, we should publish it. Again, this is the best way to ensure that scientists and doctors have ALL of the tools they need to treat disease. I'm afraid my answer to the fear that terrorists might get hold of the "recipe" and recreate their own "Superbug" will not be entirely reassuring. In the first place, creating super influenza viruses is not something to cook up in the bathtub. It is not within reach of the casual kitchen sink experimenter. It will require specialized lab equipment and materials - viruses do not grow like mold on bread, they must be specifically cultured in living cells (human cells, if it is to target humans). On the other hand - there is no guarantee that the enemies of civilization do not already have the scientists and equipment working on "weaponizing" H5N1. Choosing to suppress publication is not going to stop them. In fact, refusing to publish may rob our medical researchers of the very knowledge they need to develop effective treatments!

A Question of Ethics

So - is it ethical to perform such dangerous research that could be turned into weapons against civilized peoples? In many cases... Yes. In fact, I would argue that we as scientists have an obligation to research the greatest dangers that face our society. Research into the smallpox and polio have virtually wiped out these diseases from Western society - yet the microorganisms themselves could have devastating consequences if released from a lab. Research into botulinum toxin has resulted in not just a cosmetic treatment, but an important cure for intractable migraines. research into plant and animal toxins results in improved drugs and treatments for neurological diseases. Research with corrosive chemicals led to development of rocket fuels and the space program, with the end results of improved telecommunications, compact electronics, lightweight/high strength materials and improved medical diagnostics. Research with radioactive materials has led to energy production, medical imaging, treatments and food preparation and safety.

Each field of study has its dangers and its detractors. Denying research and publications because "it's dangerous" is short-sided at best, criminally ignorant at worst.

Yes, we need to proceed with caution...

Yes, we need to proceed with safety controls in place...

Yes, we need to proceed with public disclosure and monitoring ...

...but we need to proceed!

An Open Letter to U.S. Retailers

2011-11-23T18:03:00.001-08:00

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An Open Letter to U.S. Retailers:

You wouldn't allow your employees to be intoxicated at work.

Why are you encouraging them to work while sleep-deprived?

The frank truth is that lack of sleep produces many of the same mental effects as being drunk or high, and Black Friday will be staffed by employees operating on too little sleep. The busiest retail day of the year is also the day when clerks and shoppers both are at the greatest risk of making serious judgmental errors at potentially high costs.

The factors that could lead to serious lapses in judgment include:

Sudden shift from working during the day to working during normal sleep hours.
Long work hours
Difficulty in sleeping during the day

Many stores are opening at very early hours on the Friday after Thanksgiving. Shops which normally open at 8, 9 or 10 AM will open at Midnight, 3 or 4 AM. The employees will have to report to work 5-8 hrs early than normal, in fact, they will start work during the times of the day when they are usually asleep and all bodily functions are at a minimum. It is as if they had suddenly traveled from the U.S. to Europe, with all of the symptoms of jet lag, without the elapsed time.

To make matters worse, many of your employees will attempt to go to sleep in the afternoon or early evening so that they get a decent amount of sleep before getting up and going to work. The human body's daily cycles and rhythms involve 6-10 hours of sleep, followed by 16-18 hrs awake. Most people find it difficult to sleep when they have been awake for less than 12 hours, thus even if the employee *tries* to go to sleep at 6 PM (to be up at midnight and at work at 2 AM) they will spend a lot of time *trying* to sleep, but not succeeding. It is a well known factor of "swing-shift" workers that it takes about a week for a worker to adjust their sleep schedules from day to night shifts (or vice-versa) [Kolla and Auger, Cleveland Clinic Journal of Medicine, October 2011, volume 78, number 10, pages 675-684].

So now your employees have disrupted sleep cycles, are working during the time of night when their body is conditioned to be asleep, and they are sleep-deprived. What does that mean for their ability to function at their job? Sleep deprivation slows reaction times, impairs memory and alters judgment. A study in primates a few years ago demonstrated that following a single night of lost sleep, critical brain areas showed reduced activity, while other brain ares have to work harder to compensate [Porrino et al., Public Library of Science - Biology, September 2005, volume 3, number 9, page e299]. When sleep deprived, it is difficult to form and use short term memory - such as ringing sales and making change. It is also difficult to make critical decisions, such as identifying shoplifters or when to allow exceptions to sale terms.

Essentially, people who are sleep deprived show many of the same impairments of a person with a legally impaired blood alcohol level even though they do not show the same physical effects [Citek at al., Journal of Forensic Science, September 2011, volume 56, number 5, pages 1170-1179]. While factories, shops and offices that normally operate evening and night shifts have employees who are accustomed to working in the dark hours of the morning, most retail employees (and shoppers) are not. Thus, not only are your employees *working* impaired, your customers are *shopping* and driving while impaired. The increase in traffic incidents and police responses on Black Friday is commonly attributed to the size of the crowds, however, the increasing trend of early opening and sleep-deprived public has to be be compounding the problem.

Finally, the trend of increasingly early opening is robbing your employees of the very holiday and family time that is provided by closing businesses on Thanksgiving day. In order to *attempt* the sleep necessary to be at work at midnight or 4 AM, your employees have to shut their families out and attempt to sleep or nap during the afternoon or early evening hours. As described above, they may make the effort, but the likelihood of success is low.

It is a nice sentiment to close your business to allow employees to be at home with their families, but it all rings hollow when you steal the time back in order to be the first store open the next day - particularly with employees who are working while impaired..

UPDATE:

This is not a rant against retail or capitalism. For many years I shopped on Black Friday because it was the only time to shop *for* the kids, *without* the kids. I understand that retailers are depending on increased volume of sales at discounted prices in these economic times. From personal experience I know that Black Friday crowds mean that most shoppers will be able to visit only one or two store, thus early opening is an incentive to get shoppers in your store *first*.

My wife works in retail - operations support - and will be busy from 1:30 AM onward fixing the problems that are guaranteed to occur on Black Friday. Thus, I *will* be out in the early hours of Black Friday driving my wife to work to ensure that she arrives safely - but then, I have already adjusted my sleep schedule to be able to function appropriately after midnight, a luxury not afforded to employees working day-light shifts on any other day.

Please understand that this is a reasoned appeal, backed by scientific evidence, to reverse a trend that *encourages* Americans to work, shop, drive and make decisions under conditions that impair all of those functions. We may *not* be able to reverse the trend, but at the very least I hope that by understanding these effects we will be better informed if/when incidents occur due to sleep deprivation.

Monday Funnies

2011-10-24T17:30:00.000-07:00

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I'm back!

Sorry, but *someone* seems to have broken the blog. I can only log in from home, and not from any of my computers that also do work-related material. I have narrowed the problem down to virus/malware filtering which seems to think the site may have content problems. In the next few days I will be trimming content and comments to see if I can find the problems and get back to regular posting.

Enough of that! This is Monday! It's supposed to be Funny!

Today's lab-related humor comes from Brant Parker Johnny Hart's The Wizard of Id.

I frankly had forgotten the lab-type humor that Parker and Hart (and later Brant Parker's son Jeff) often injected into the strip. The Wizard is cast in the role of scientist, with often bizarre lab subjects, such as Ratso, above.

The Wizard of Id is also the source of one of my favorite explanations of the discrepancy between athlete and academic salaries: "No one ever bought a ticket to see a scientist!"

Go search the comic out, find the books, search through old newspapers and archives. It is worth the effort.

Enjoy!

Monday Stuff

2011-10-10T16:31:00.000-07:00

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Guest Blogging Courtesy of K. Mata - the Goddess of Lab Rats!

This blog has commented before about medical marijuana and medicinal cannabinoids. Here's an article about what it's creator calls "A Good Drug Gone Bad." Thelink is to a story in the LA Times about the creator of JWHcompounds, major ingredients of 'spice' and other syntheticmarijuana products sold until recently in gas stations asincense. It should be stressed that the scientist creator did not distribute this drug. The formula was lifted from the lab and form publications. It is manufactured and sold from China as "plant food."

I've included the first few paragraphs below...

http://www.latimes.com/news/nationworld/nation/la-na-killer-weed-20110928,0,2646834.story

Scientist's research produces a dangerous high

John W. Huffman created synthetic marijuana fortests on lab animals. His formulas ended up in the hands of head shops, whichhave created substances that can lead to seizures, hallucinations andconvulsions.

ByDavid Zucchino, Los Angeles Times

September 28, 2011, 3:46 p.m.

Reporting from Sylva,N.C.—

John W. Huffman is abearded, elfin man, a professor of organic chemistry who runs model trains inhis basement and tinkers with antique cars. At 79, he walks a bit unsteadilyafter a couple of nasty falls.

Relaxing on his back porch in the Nantahala National Forest, watchinghummingbirds flit across his rose beds, Huffman looks every bit the wise,venerable academic in repose.

But this courtly scientist unwittingly contributed to the spread of"designer marijuana" so potent that the Drug Enforcement Administrationhas declared some of what he created illegal.

Huffman's years of scientific research at Clemson University on theinteraction between drugs and brain receptors led to so-called fake marijuanawith effects far more powerful — and dangerous — than garden-variety marijuana."Spice," "K-2,""Skunk" and similar products made using the chemical compounds heformulated have surged in popularity in recent years.

That prompted the Drug Enforcement Administration in March to temporarily list"stealth marijuana" products containing three cannabinoid compoundsinvented by Huffman as Schedule 1 drugs illegal to sell or possess.

Some interviewers and critics have blamed Huffman for turning an entiregeneration onto "monster weed."

"It's become a royal pain in the rear end," Huffman said the otherday, reflecting on the unwelcome attention his research has received. "Ihad a TV station in Moscow accuse me of trying to poison America's youth."

In that interview, live on Russian radio, he said, his responses seemed slowbecause of a satellite delay — so slow that the questioner accused him ofsmoking his own creations.

In a separate conversation, a BBC interviewer "basically asked me when Istopped beating my wife," he said. "They accused me of creating allthese horrible drugs."

But Huffman laughs as he describes emails assuming he has created a super formof medical marijuana or hasprofited by designing lucrative marijuana substitutes. "We were not. Itwas all just basic science," he said. To counter misinformation, he andClemson have devised a boilerplate statement describing his research andwarning against consuming synthetic marijuana.

That hasn't stopped alert entrepreneurs from using Huffman's formulas,published in scientific journals. Their products, often sold as "herbalincense" and smoked like traditional marijuana, can produce seizures,hallucinations, tremors, paranoia, convulsions, high blood pressure and rapidheart rate, say emergency room doctors.

Poison control centers have received 4,500 calls over the last two years frompeople using fake marijuana, according to the American Assn. of Poison ControlCenters.

The Value of Repetition...

2011-10-08T14:01:00.000-07:00

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In my guest Blog for Sarah Hoyt last Thursday (Oct. 6 - ) I discussed the value of looking toward the future as a Lab Rat - knowing that as long as conditions remain the same, repeating our past actions is valuable - but the moment conditions change, too much "memory" in the form of repeating past actions, can be detrimental.

I stated:

"A popular saying among some groups such as the Baen Barflies is that insanity is doing the same thing and expecting different results. Likewise, insanity is doing different things and expecting the same results. Yet sometimes we have to change strategies in order to get a better result, as in the transformation from traditional to indie publishing. I’m not an “insider” to this phenomenon, but I certainly recognize the signs and symptoms from behavioral psychology."

There were many good follow-up comments to the blog, and I wish I had been able to engage in the responses and replies. Unfortunately, most took place while I was at work, and it was a particularly busy day. However, one comment merits a response here.

"David" October 6, 2011 at 12:30 pm replied

quote: Likewise, insanity is doing different things and expecting the same results

I take issue with this, there are frequently many different ways to get to one result. some ways may be more efficient than others, and it’s usually true that if you are picky enough the results are not ‘identical’ (after all, the process you go through has side effects), but if you are looking for ‘equivalent’ results there are frequently many ways to get to the result.

David and I have had some give and take on other issues in other forums, but that is immaterial. However, I take issue with David's comment. Granted, equivalent results can be obtained, but the same results never are. Most importantly, how we learn and behave is significantly altered by the approach we take to obtain a result.

I will forever remember the example taught in my first lab psychology/animal behavior course:

A rat is placed in a cage with a levers. If the animal pressed the lever, it heard a tone and received a food or liquid reward. My professor, as a student, was training his rats and had one that would never purposely press the reward lever. The rat would bump up against it, rear up and sniff the cage top and lean against the lever, latch onto the cage top and fall on the lever, but never reach and press the lever. Now this is normally a very easy behavior to train to the rat. The instructor for that course suggested a barrier be placed in the cage, such that the lever was at the end of a corridor, and the rat could not "accidentally" bump the lever. Rats are naturally curious and will usually explore under those conditions. Unfortunately the animal chose to climb over the barrier, stepping on the lever on its way down. If the barrier was removed, the rat would not press the lever. My professor told us he tried for weeks to teach the rat the appropriate response - his other rats learned it in 5 days, but this rat could not learn it in 5 weeks.

So, why did that happen, and what's the "punch-line" for this column? Well, to teach a rat, you need consistent conditions so that there can be an association between the action and the outcome. In this case, the rat obtained an equivalent result - the food reward - but it never learned to associate deliberately pressing the lever with the outcome. To that rat, it was the act of climbing over the barrier that resulted in reward - it obtained food mysteriously whenever it explored, but never learned that it could produce a reward as a consequence of its own actions.

A corollary to this example is something I see quite often when teaching students: They train a rat to perform appropriately when the time delay between action and reward is negligible, but as soon as the delay is increased, the animal performance deteriorates. To fix this, the student decreases the delay, then makes the trial easier by eliminating one or more choices, then they try adding cues, then changing the reward - often all at once or on successive days. What this means to the rat is that it never has a stable context in which to learn the appropriate responses. We can teach animals and humans to do many things as long as there is a stable context - Action A results in B - during the learning phase. We can even teach them to be flexible and learn new mazes, as long as we introduce consistency in the learning/relearning phase.

Alvin Toffler called it "Future Shock" - the inability to cope with rapid change. Deprived of enough stability to learn the rules, some people never learn how to deal with change. What distinguishes the lab rats - and people! - who can cope with change is that they have in fact learned a few basic rules of how to respond to changing context. Most importantly, they learn just how important those "picky" differences are.

So, I argue that there are in fact a few ways to get equivalent results. However, each different method teaches different rules - and if we keep changing the rules, nothing can be learned. Its one reason why rote recitation used to be taught in school - and still is in professional schools. Perhaps it would be more appropriate to say "... insanity is: constantly changing the rules, but nevertheless expecting the same results." On the other hand, I stand by my original statement.

We can learn a lot form Lab Rats.

Guest Blog on "According to Hoyt"

2011-10-06T13:50:00.000-07:00

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My friend Sarah A. Hoyt has been blogging about the craft of writing as well as changes to the traditional models of publishing that are on the horizon. Yesterday she wrote "In the Future we're all Ducks" (http://accordingtohoyt.com/2011/10/05/in-the-future-we%E2%80%99re-all-ducks/) referring to the manner in which Disney's Donald Duck character seems to go from job to job in each episode - one time he's a beautician, next time he's a janitor in Uncle Scrooge's bank. The fact that Donald seems to switch between jobs doesn't seem to matter to him. [By the way, Sarah, my wife reminds me that despite this seeming lack of care, Donald is never truly satisfied!]

Sarah goes on to talk about how we can learn from Donald and improve our skill set by learning things we would not previously consider. For myself, I always thought I'd be a scientist or a surgeon (or a jet pilot, but I was asthmatic and didn't have the eyesight). Computers other than the huge government behemoths didn't exist, but as they were developed, I considered that I might be a programmer. Little did I think I would become all three - I am a scientist who performs surgical procedures in the lab as needed, and I program most of my own analyses. I never really thought that much about being a writer, but here I am working on both nonfiction and fiction for the SF market.

But back to Sarah's post, I argued that we are not Ducks, but Lab Rats. I started to lay out my logic, and Sarah said I should just write it all down and guest-blog it for her. Incidentally it also gives her a bit of a breather since she has been out of town for two weeks and needs to get some things done before getting back to writing.

So head on over at According to Hoyt, and read my guest blog - Not Ducks, but Lab Rats (http://accordingtohoyt.com/2011/10/06/not-ducks-but-lab-rats/). It's a story of behavior and flexibility, and the sad consequences of lacking behavioral flexibility.

Enjoy!

Monday Funny

2011-09-26T14:47:00.000-07:00

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Blatant Plug.

One of my new favorite webcomics is Ninja Nun (http://www.robertahoyt.com/Comic92.html). Click on the crossed rulers below the comic and start from the beginning. No, it's not science based, but I happen to know that artist has a respectable pedigree in science - Robert Anson Hoyt is a published science fiction author, and named for the SF author Robert A. Heinlein (R.A. Hoyt having been born on R.A. Heinlein's birthday). He comes from a family of SF writers and is himself a pre-med student. In fact, he has even been known to refer to himself as a "lab rat"!

If there is any doubt that Robert A. Hoyt has a wicked sense of humor, check out the comics immediately following and preceding the one linked above, then check out this highly appropriate bonus comic (http://www.robertahoyt.com/Bonus3.html). Yes, Robert loves ties. No, we couldn't get him to stop wearing them even in the lab, cleaning rat cages. He'll make a fine surgeon someday with his attention to detail and cutting wit.

So sharpen your ruler, sit back and enjoy the adventures of Sister Agnus Day, the "Ninja Nun."

Reading minds?

2011-09-23T18:56:00.000-07:00

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Hat Tip to Andrew who brought the following to my attention:
http://gizmodo.com/5843117/scientists-reconstruct-video-clips-from-brain-activity

All I can say is WOW! Wow to the technology. Wow to the science, and Ouch, to the poor subjects who spent 3 hours in the MRI scanners.

To the journalist/publicity department... yeah, not so much.

This is really neat stuff. The scientists at UC Berkeley used magnetic resonance imaging to map brain activity as their subjects viewed a number of video scenes. Most of the readers to this blog probably know that MRI is used to take pictures of the inner structure of the brain and soft tissues of the body. Chemists and physicists may remember that the basis of MRI is nuclear magnetic resonance - in a strong magnetic field, hydrogen bonds orient and spin in the same direction. A radio signal causes them to flip orientation, and the resulting energy release can be detected. Water molecules have plenty of hydrogen bonds, brain and soft tissues have plenty of water, thus MRI is used to map the density of water in the brain. MRI can also work with oxygen, and blood contains both water and oxygen.

Functional MRI (fMRI), as used in this study, goes one step further, it maps changes in brain activity on based on the blood flow to active brain areas. The apparatus is a bit cumbersome, and it's not exactly "real-time" but fMRI can tell a lot about overall brain activity.

What this study shows is that the scientists were able to build a database of brain activity in response to video. Then when an image was shown to the subjects, the computer was able to determine which image was shown to the subjects. Essentially what the experiment did was to reconstruct the brain's code for visual scenes.

This is neat stuff!

Understanding the brain's internal coding scheme is a major accomplishment, and this experiment goes a long way to demonstrating exactly that.

But reading dreams? I'm sorry, but that's way too much of a stretch for this experiment.

(1) The fMRIs were taken as the subjects were viewing various scenes. They were not taking while "imagining" scenes, from recollections, or from dreams.

(2) Vision activates multiple areas of the brain that are not active during imagining or dreaming. The primary visual cortex and input pathways are not active unless the images are actually present to be viewed. On the other hand, the sensory association cortex and memory systems are active during both vision and recollection.

So in short, a reconstruction of dreams or memory is missing half of the data that would be present when the subject is viewing scenes, images and video as in the current experiment.

While extremely important and exciting, the UC Berkeley findings are not mind reading or even dream reading (ala "Brainstorm"). Can the technology tell us a lot more about how the brain encodes information? Yes. Is it mind reading? Well, not exactly, and certainly not in "real-time."

However - Go Berkeley! Keep up the Neat Stuff!

The unfortunate truth...

2011-09-18T12:48:00.000-07:00

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Well, this is something I hoped not to have to do.

No, I am not stopping this blog, but I need to adopt an irregular update schedule - in fact, it should be fairly obvious that I already have.

There is an unfortunate truth about blogging... if you do it right, it's a job. The unfortunate part is that it is quite often a second, third or fourth job on top of other duties. I started this blog as a way to talk about Science and provide structure and feedback for writing The Lab Rats' Guide to the Brain. It has been successful. I appreciate the readers and great questions. They have assisted me in writing and refining what I have written for the Guide.

However, I do have a day job. As medical school research-and-teaching faculty, my employer figures that it is a 55-60 hr/week job. That includes time at home working on writing up scientific results and set-up for teaching lectures. Reviewing scientific manuscripts, and grants, and writing my own grant applications is extra. Preparing teaching materials (for those of us with more than 80% research commitment) is extra. Committee work (essential for promotion) is extra. Putting in the additional effort to be promoted... is extra.

So the Day Job is job number one. The ancillary teaching, reviews and extra work that will assist in my promotion and tenure prospects next year is Job 1.5. Family is Job 2, my fiction writing has been Job 3 and I had hoped that the blog would fit in nicely as Job 4.

It hasn't worked that way. I tried an every-other-day schedule and a three-nights-a-week schedule, and this Blog became Job 2, and nearly Job 1.5. I suppose I write too much in each blog, it takes me 1-2 hrs for each Guide post because I am researching details, searching out illustrations (public domain if possible) and comparing results with existing websites. There have been times I could take an hour out of the day job and write part or all of a blog - usually while eating lunch or waiting on a computerized analysis to complete - but those opportunities have become fewer and further apart.

But the most unfortunate truth of blogging is the effect on creativity. I have written before about the fact that I can write science or I can write fiction, but cannot intermingle the two. I have to clear my head of the professional work in order to write the recreational stuff. The Guide has been beneficial, in that it *is* science, and I do not have to completely shift gears from my work in order to write.

But it has nevertheless impaired my writing ability. I have three writing commitments due this fall, and have not been able to work on any of them in three months. I must make time to complete the projects... at a time when I find myself having to do more grant and manuscript writing at work. "Something's gotta give," and I am afraid that it is regular blog posts.

I will still continue to blog. I will post the final sections of the Guide, comment on new and interesting Science, and continue to answer questions.

I appreciate all of my followers and occasional readers, and encourage you to sign up to follow this blog either via Blogger or Facebook (NetworkedBlogs). I will continue to email the blog to Sarah's Diner in Baen's Bar, whatever form that forum eventually takes. Sign up, and you will be notified or emailed the blog when it posts.

Again, I am not discontinuing, just moving to a less regular posting schedule. I will continue blogs at least weekly, and will try to continue Monday Funnies as long as I have material.

Thanks for your understanding...
-Speaker

If it's Wednesday...

2011-09-14T13:51:00.000-07:00

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...it probably means I'm trying to figure out what to blog!

Before returning to the mailbag posts, I want to take the time to post some links to recent video projects. The flip-side to Teddy's Rat Lab is the TR Productions home page which features photos and videos from various science fiction panels. Some of the earlier work can be found at http://teddroberts.com, complete with downloads in multiple file formats. I tried hard to work out a streaming video service for the website, and need to get some of the more recent videos linked on-site.

All of the more recent work can be found at my YouTube channel: http://www.youtube.com/TeddRoberts once the length and size restrictions were eased. Particular features of the channel include the recent Dragon*Con videos. At the upper left is the "Air Shark" swimming through the lobby of the Atlanta Hyatt Regency. Below left is the flash mob tribute to 2011 Campbell Award nominee, NY Times bestselling author Larry Correia and his Monster Hunter International series.

Several of the videos are short subjects, promotions, teasers, and music ("filk") - some are much longer full panels and skits from various SF conventions. For Music, check out "Monster Hunter Ballad" written and sung by Gray Rinehart (by the way, there's more coming from Gray as soon as I can get the video processed). For pure zombie-hunting fun, watch "Killing the Undead" a pro-writer panel from last year's LibertyCon - but for absolute zaniness, there's "The Making of Ghost: The Movie" in several versions, the YouTube HD release of the Dragon*Con 2008 version, and the download version of the LibertyCon preview skit available on the website.

There are many panels uploaded, and more to come. Keep watching for new releases. Like, subscribe or friend the channel, share the videos, comment, and rate them.

Enjoy!

Monday Funny

2011-09-12T19:07:00.000-07:00

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Once upon a time there was a "scientific" journal. Unlike most journals that publish results from experiments that have been repeated and statistically confirmed, the journal specialized in really neat results that `looked real, but couldn't be repeated. Even though founded in 1955 to publish science humor and satire, the Journal of Irreproducable Results had a serious side - being the last resort for publishing results that could not (will never, and probably should never) be replicated.

In 1994, there was a bit of a tiff with the new publishers (who bought out the old publisher), and the editor and most of the staff left to found a new magazine - the Annals of Improbable Research. Like its predecessor, AIR takes a humorous, even satiric look at scientists and science research. It particularly seeks out factual research with a whimsical bent.

The "AIRheads" of A.I.R. invite you to visit their site and read about the aerodynamics of whiffle balls (http://improbable.com/2011/09/11/aerodynamics-of-odd-balls/), find out whether most physicians hang their stethoscope to the left or right (http://www.hopkinsmedicine.org/doctors/results/directory/profile/9451649/emmanuel-antonarakis - linked on the A.I.R. site, Sept. 11, 2011), witness bad poetry readings and satirical songs (http://www.youtube.com/watch?v=p0UlNkag4Vk), or even check out the Ig Nobel Prize ceremony coming up Sept. 29th (http://improbable.com/ig/2011/).

Just remember, if you laugh your funny bone off, it's a humerus!

PS - Addendum: I did not mean to slight The Journal of Irreproducable Results. BOTH journals provide a slightly serious, mostly fun look at science. The J.I.R. site is: (www.jir.com) and I am certain they would appreciate our patronage!

2011-09-09T18:27:00.000-07:00

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I haven’t stopped to answer questions based on the Lab Rats’Guide to the Brain for quite some time. I have received comments in the blog, as well as in the Baen’s Baronline community. Unfortunately Ihaven’t been entirely timely in answering the ones that require more than justa quick answer – but I do save them for later use.

So for the next several days I will work through the backlogand answer your questions about the brain. So without further ado…

[squeak]

What’s that, Ratley?

[squeak]

Um, yeah, I suppose I should.

[squeak]

Right. Ratley isgoing to gather the other LabRats around for this. Since I still have a scientific conferenceand Dragon*Con this week, I’m going to let them tackle the mail while I finishmy two presentations for the meeting. So, I’ll just set up this automatic translator and get back to fixingslides.

[squeak... er, excuse me. Hi. I'm Ratley, and I'msupervisor of the LabRats. What Speakerseems to have forgotten is that it has traditionally been the job of theLabRats to answer the mail. The factthat he hasn't let us out of the lab much these past few months is one of thereasons we've gotten so far behind in reading the mail. We each have our different areas ofexpertise, so the LabRats will share the task of answering questions. For the first couple of questions, I'm goingto let Ratso answer. He's pretty smart,even if he does prefer to spend too much time in the kitchen and talk like ...well, a rat!]

Ratso: Yo, Ratboy, I*resemble* dat remark! Okay, on wit' daprogram heah: Chris writes: “I’m working on a story where my characterhas to get used to his new super abilities. Just how fast does the brain process? If thoughts, movements and reflexes were to be sped up, how hard wouldit be for my character to cope and learn how to use them?"

Well, Chris-boy, it's like dis – da brain is only as fast asits parts. To understan' how fast datcan be, ya gotta figger out how fast is each link in da chain. Da neurons, well, dey's pretty fast. Takin' the time from the first chemicalactivation of a synapse to when da action potential starts is about 2milliseconds. Action potentials (http://teddysratlab.blogspot.com/2011/02/piece-of-action-potential.html)travel to the other end of da neuron at about 10 meters per sec. If da neuron is a *long* sensory or motorcontrol neuron for da body, it has a special insulatin' coating called"Myelin" dat speeds up da action potential to about 100 meters/sec.Once da action reaches da end of the neuron, neurotransmitter chemicals arerelease to start da process all over again in da next neuron. Da chemical part takes about 2-3millseconds.

So each link in da chain, dat is, each neuron"synapse" takes about 5 millseconds, and it takes an action potentialless than 10 milliseconds to travel either from brain to brain area, or frombrain to hands – about 20 milliseconds to get to da feet. Dat's pretty slick, if ya ask me! Multiply dat by about 4 or 5 times forconnections between neurons and parts of brain controlling an action. I like connections. I'm a connections kind of guy myself!

So yeah, da brain can process pretty fast, almost anythingya wanna do can be completed in about 100 milliseconds. If'n ya wants to write a story wit'everything speeded up, ya can prob'ly get about 10 times da speed outta justmakin' the chemical and electrical connections more efficient, but like anygood exercise, ya gotta learn ta use it. In fact, it'll be jus' like any new skill: practice, practice, Practice!

***

Ratley: Thank you, Ratso. Perhaps you should get back to the stockroom, there's a fellow namedGuido back there saying something about kitchen supplied that fell off of atruck?

For the next question, perhaps we should defer to ourresident master of motor skill, Nestor:

Nestor: Why thank youold chap, that's mighty kind of you. Bea good lad and hand me that letter then? Ah yes. In response to “The SixSenses (and maybe more…)” Anonymous asks: “What about the ability to do complex tasks requiring fine motor skill,with your hands out of sight and in all sorts of odd positions? I do that quiteoften when working on cars and other mechanical things. It's like I can"see" with my hands, often it helps if I close my eyes.”

Dear Sir:

What you are describing is commonly misnamed as "musclememory." A skill practiced to apoint where it becomes automatic. Themuscles move the way they are supposed to every time, you don't have to thinkabout it.

In reality, this should be termed "cerebellarmemory." The cerebellum is the partof the brain most responsible for coordinating movements. It is quite heavily connected to all thoseparts of the brain involved in a movement or reflex. For instance – when moving your arm, you mustmove the arm muscles and joints, but you also turn your head, shift your weighton your feet, twist slightly at the waist and often look at the movement. If you don't look, you'll probably do it ok,but you may not be quite as accurate in the motion. Now try to move your arm while keeping therest of your body completely still! Quite a bit of bother, no? Thatis because the brain issues all of those commands, coordinated by thecerebellum, and when you consciously override the reflexes, the cerebellumrequires all new programming. Sort oflike learning to raise a single eyebrow.

Soldiers and athletes understand the concept very well. Actions must be learned so well that they areautomatic – however it really is the brain learning, and not the muscles. As for your question, it's all the same,righty-o? Because we have learnedhow our muscles move while we watch them, it is right simple to imaginethose movements, then perform them with our eyes closed. You "see" with your hands becausethe brain uses all of the information about movement and position and thencalls upon memory to fill in the missing pieces. All of the connections from the cerebellum tothe motor and sensory areas of the brain, plus the connections to visual andauditory tracking centers in the brainstem provide a "map" of thebody in 3-D space. Quite amazing, if Imay say so myself.

Now, if you will excuse me, my tail seems to be caught in a…Oh bother!

***

Ratley: Thanks,Nestor. We'll send the Jaws of Life infor you, don't worry.

Sandra writes: DearSpeaker:

My daughter's domesticated petrats have been vocalizing a lot lately. The other day I walked into her roomand told her it was time to get up. A rat (in the cage) poked its head out ofits sleeping hammock and said *squeak-squeak*. Later, as the two rats were outof their cage, playing, they froze when the big black dog stepped into theroom. I sternly told the dog to leave (she's not allowed in that room) andafter the dog left, the biggest rat rushed to my side, staring at the door, andgrowled and squeaked. I've never heard her (the rat) make these sounds before,and it sounded like she was scolding the dog.
I realize we humans tend toanthropomorphize our pets, but could these rats be trying to communicate? Andwhat about the personalities these rats seem to have? For many people, rats arevermin and pests; for cats and dogs they are prey. How can these rats be socharming?

[squeak!]

Ratley: What's that,Ratface? Cousins you say? Yes, Indeed. They must be!

Dear Aunt Sandra – (for if the rats are our cousins, youmust be our Aunt!) – domestication of any animal is a learned process. What you are describing represents twoaspects of learning that apply to many animals. If you have ever watched circus animals, movie dogs or the "Walrus,Otter, Sea Lion" show at Sea World you have seen the results of what iscalled "operant conditioning." Most folks should recall reading or learning about Pavlov's experimentsin classical conditioning. Pavlov rang abell simultaneous with the smell/taste of food. The dog salivated at the food stimulus, and eventually learned tosalivate at the sound of the bell alone. In behavioral terms, we talk about an "unconditioned stimulus"(UCS) – that is, a stimulus that produces the desired response withoutlearning. In the Pavlov example, smellof food is the UCS and salivation is the response. Then there is the "ConditionedStimulus" (CS) – this is a stimulus (bell) that we *want* to produce thesame response as the UCS. So we presentUCS and CS together for a *lot* of repetitions – usually with the CS occurringbefore the UCS. Eventually theconditioned response (salivation) starts to occur after the bell, but beforethe smell of food. Once that happens, wecall it a "conditioned response" (CR). Once our experiment begins tolook like this: CS – CR – then UCS, we haveconditioned the animal and can even omit the smell of food (UCS) and still getsalivation (CR) just by ringing the bell (CS). Voila - Pavlov's classic experiment in behavioral conditioning, alsoknown as "classical conditioning."

Operant conditioning differs in that we actually teach theanimals a chain of UCS stimuli, and those stimuli require the animal to *do*something. In the Sea World showexample, the sea lion is conditioned to know that ringing a bell means a foodreward will be given. This is classicalconditioning, but then we add a twist – now the sea lion gets a chance toexplore the bell – if it rings the bell itself, it gets a fish! This is the first essential step in operanttraining, the animal makes its own response and receives a reward. To make more complex behaviors, we just trainin one preceding step at a time – before the sea lion can ring the bell, itmust climb some steps. So in this stepwe have two operant phases: (1) climb steps, in order to be able to (2)ring bell, to receive the reward. It'sjust like training dogs, horses, or even people. Once enough steps are "chained"together, our sea lion becomes the star act and appears to be behaving justlike a human – but it's only conditioning at work.

Your pet rats have become conditioned. They know which humans feed them, take themout for exercise, and protect them from predators. This is where the second aspect of learningcomes in: dominance. Normally, dogs arepredators to rats, as are humans. Trustme. We lab rats know all aboutthat! However, in caring for ourcousins, and keeping the other predators away (!) we come to recognize youhumans as the dominant creatures in our environment. As long as we remain conditioned to you, andyou protect us, we'll act submissive to you.

Now submission comes in many forms. Speaker tells us stories of working withprimates. If there's one big mean monkeyin a colony, the other monkeys are submissive, and most will not challenge the"Alpha." However, if the Alphaattacks a smaller monkey and a human intervenes, the lesser monkeys lookto the human as Alpha (and sometimes even the Alpha will defer to thehuman). The human is the more dominantcreature and protector. In animalbehavior terms, that's usually called "mate," but is also"companion" with the commonly domesticated animals such as dogs andhorses.

So what you are seeing is a bit ofanthropomorphization (hmm, Ratfink must have left that word lying around here)but also a result of the conditioning and dominance hierarchy among animals.

But then again, it might just be that our cousins are a bitsmarter than you think!

***

Oops, here comes Speaker, time to get back to work.

Speaker: Thanks,Ratley. My meetings are over, as isDragon*Con. There's a few more lettersin the mailbag here, and I'll try to get to those next week. I hope the answers were informative, but youcan never tell with LabRats!

Until next time….

Dragon*Con After Action Report

2011-09-07T15:01:00.000-07:00

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Last weekend was Dragon*Con - the largest Science Fiction / Fantasy / Comic / Anime / Gaming / Media convention in the southeastern U.S. For those of my readers not familiar with Dragon*Con, but who may have heard of San Diego's ComicCon, Dragon (or D*C) is a bit smaller... "only" 45,000 in attendance. Whereas ComicCon is essentially a tradeshow, originally about comics and graphic media, it grew to be the premier "trade" show for SF and Fantasy TV shows and movies.

On the other hand - D*C is about fans - yes, there were panels filled with the stars, writers, directors and producers of TV and movies - but there were also tracks for anime, producing animated music videos, costuming, writers, survivalists, dark fantasy, noir detectives, alternate history, SF literature - and yes, science. These tracks gave a chance for interaction between fans, writers and all interested parties. THis is the first of several blogs regarding D*C, but the only one to run exclusively in this blog space, so I will concentrate on giving an overview of the "Science in Science Fiction" nature of the panels I experienced at D*C.

To start with, I participated in panels in the SF Literature, Apocalypse Rising and Science tracks. Panel titles included: "Year 2" (rebuilding civilization after the apocalypse), "Science and Science Fiction" (how science informs the arts and how art informs science), "Global Insurgency" (how wars will be fought - and survived - in the future) and "Zombie Science" (a look at fact and speculative fiction about zombies).

For "Science and Science Fiction, my co-panelists included Stephanie Osborn, Les Johnson, and Chuck Gannon. Steph and Les are real rocket scientists and Chuck is a professor. All three are published Science Fiction writers, so we really did know what we were talking about. The panel subjects discussed how good science fiction relies on believable science (and sometimes on just so-so science) so as not to be fantasy in reality. We discussed how much can be left to the reader, what needs to be explicitly explained, and when the accuracy of science has to make way for good storytelling. One of the most notable outcomes of the panel was the revelation that so much of what we take for granted in modern society - wireless telecommunications (cell phones and satellites), realistic broadcast entertainment (HD TV), weather forecasting (satellites again), transportation, personal computers and even voice-sensitive computers you can carry in your shirt pocket (smartphones) have been inspired by science fiction.

In the Apocalypse Rising panels "Year Two" and "Global Insurgency", SF writer and SurvivalBlog contributing Editor Michael Z. Williamson scared us all into realizing that urban environments are not conducive to survival after the fall of civilization. On the other hand, they'd make great resource areas (if they can be reached and aren't picked clean) for rebuilding civilization. Conversations on these panels included such topics as rebuilding the sciences, what trades and knowledge are essential for survival, how to find information on basic medical care/first aid, and how to prepare for "everyday" emergencies such as storms, floods, fires, and earthquakes.

Finally, in "Zombie Science" we discussed the real science behind zombies. The undead represent fear of the unknown, the psychological uncertainty of "the other," and a pretty good metaphor for disaster preparedness. With 4 scientists and 2 writers, we discussed where the zombie myth comes from, dissed the various fictional settings and sources of zombies (Parasites, Yes! Radiation, No.) and talked about actual biological parallels to the "mindless" behavior that is one definition of zombiehood. We also used biology and physics to come up with the best means of defense and dealing with zombies (thermobaric explosives for the win!).

All-in-all, Dragon*Con is a great place to talk science and science fiction, not to mention engage in some great conversations (such as the one mentioned Monday where regarding things that go Boom! and the fun of model rocketry gone awry!). I'll be writing some more blogs to be posted in other venues, but I'll link them here when they are up. I'll also post links to videos and podcasts of the panels as I get them prepared.

---

Up next - Mailbag posts where I *finally* answer those questions you've mailed in.

Until next time - take care of your brain - after all, the Zombies will if you don't!

Monday Funnies - Dragon*Con version

2011-09-05T18:58:00.000-07:00

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Just returned from Dragon*Con. Lots of fun, not a lot of sleep. Today's humor links are not specifically science related, but... I was listening to the panel on webcomics...

For context, I was specifically waiting for Howard Tayler, creator of Schlock Mercenary (which I linked in a previous post), and he was moderating a panel on webcomics. There were two panelists in particular whose work I appreciate - who sometimes include humor that touches on science - and whose humor not only includes some things with which I am familiar, but who will have some Dragon*Con-related content in the near future.

I'll get to those links in a minute. But first:

Howard Tayler is one of those authors who can easily "hold court" in a room of fans and friends irrespective of location. In the car, in the restaurant, in the hospitality suite - Mr. Tayler can sure tell a story. That is why his webcomic, Schlock Mercenary is more than just a daily comic, it is a story told in graphic, serial format. He claims that someone else is the inspiration for his "resident mad scientist" Kevyn Andreason, but considering the tales he told of Boy Scout camp cooking, model rockets gone awry, and miscellaneous things that go boom, it is clear that Howard Tayler retains a bit of that mischievous mad scientist nature himself. I will reiterate that of all of the webcomics I read, Schlock Mercenary remains at the top of those that tickle my funny bone.

And now for those other webcomics: "The Devil's Panties" I admit, I don't always follow it, but when I do, I find it to be a great humorous look at life. Then there's the artist. Spend any time around Jennie Breeden and you can't help but feel her infectious energy and enthusiasm. From the big boots to threatening men in kilts with a leaf-blower, SF conventions without Ms. Breeden in attendance do not know what they are missing. "Kevin and Kell" One of the great mismatched couples of SF and fantasy. Bill Holbrook is acknowledged as one of the most experienced and skillful graphic artists. The link is to his Sunday Dragon*Con tribute strip. I think he captured it pretty well.

Over the next week I will resume regular blogging. Thanks for your understanding, I needed this break to recharge. Up next we have mailbag posts featuring Brain Science questions from readers, a couple of science and science fiction panel reports from Dragon*Con, then we will resume The Lab Rats' Guide to the Brain with topics on "Brain disorders as plot devices."

Thanks for your patience, welcome to new readers. Check out the backlist of blogs at right for content from The Guide and other brain science topics.

Enjoy!

Monday Stuff...

2011-08-29T17:00:00.000-07:00

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This past week, while teaching the medical students, we discussed the origin of gastric ulcers. Until the last 25years or so, the medical field thought that stomach ulcers were caused by a combination of stress and the foods we ate. Spicy foods, rough foods, certain combination of carbs all increase stomach acid. Stress and lifestyle can also lead to increased stomach acid. These factors, when combined, must be producing ulcers, right? After all, what is the main complaint of people suffering from ulcers? Pain with eating or ny time stomach acid is increased.

Actually, no,about 70-90% of stomach ulcers are associated with a bacterial infection. Heliobacter pylori is the culprit, and it has been found to cause gastritis (inflammation of the stomach lining) and significantly contribute to ulceration. What? A bacterium living in the highly acid environment of the stomach? No way!

Back in the 80's Australian pathologist Robin Warren and Australian physician Barry Marshall isolated the "acidophile" (acid-loving) bacterium H. pylori in the lab and put forth the highly controversial theory that a bacterium caused gastritis and ulcers (Marshall BJ, Warren JR (June 1984). "Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration". Lancet 1 (8390): 1311–5. doi:10.1016/S0140-6736(84)91816-6). It was hard to get the medical establishment to take the theory seriously, in fact, it took 10 years for the National Institutes of Health to publish a consensus statement that ulcers could be successfully treated - even cured! - with antibiotics (http://consensus.nih.gov/1994/1994HelicobacterPyloriUlcer094html.htm).

To prove his point, Dr. Marshal drank a beakerful of H. pylori culture. He became ill within days, and by ten days, endoscopy showed that he had full-blown gastritis with the beginnings of an ulcer. A one-week course of antibiotics cured the condition. Ergo, treating ulcers with antibiotics has become the accepted therapy of the 21st Century - not to mention that Warren and Marshall received the Nobel Prize for Medicine in 2005.

So... one of my students asked me: "Dr. R- Would you have made such a sacrifice in the name of science?"

I paused. Would I? Like that? No. Probably not. "Not even for the Nobel Prize?"

Well, maybe, but understand, Warren and Marshall did not know that they would win the Nobel. In fact, most recipients do not receive the Nobel until 20-30 years after they made their breakthrough.

So again, no, likely not - after all, Mrs. Speaker would probably be very mad at me.

Still, I do know scientists who have sampled their own products - usually in the pharmacology realm. The famous case of course is Dr. Timothy Leary and LSD, but I also know of at least one instance of a scientist testing a drug on themself that they hoped could some day provide relief from dementia and Alzheimer's disease. In fact, I can say that based on my work with neural prosthetics, if I ever find myself in need of one, I would volunteer to test a brain-machine interface.

After all - isn't that part of what Science Fiction is based upon? The noble, famous (on infamous) doctor slaving away in the lab, making the ultimate sacrifice for the betterment of Mankind? (or at least to come up with a better Frankenstein Monster!).

On that note - Here's the latest installment in Monday Funnies: Quantum Vibe - about a slightly mad scientist and his assistant. http://www.quantumvibe.com

I particularly like this recent one: http://www.quantumvibe.com/strip?page=179 "For most scientists, life is all about laboratories and endless incremental experimentation and publishing in journals."

But some do jump in with both feet, drink the culture, and make history.

That Medical Student Syndrome...

2011-08-24T17:00:00.000-07:00

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...No, not that one [where the think they've got every disease they study]... the other one...

It's the one where students try hard to ask their professors a question that the professor can't answer.

To be fair, Medical Students aren't all like that. I may have mentioned that I am currently working in the medical school curriculum, and some of my students may even be reading this. They are smart and curious, it's a prerequisite for medicine, but some students can take it a bit too far - and they often know it.

Also, believe it or not, this is meant to be a humorous post. In retrospect, I have found these incidences to be quite humorous.

Back to the Medical Students: We have a program that emphasizes "Case-centered" learning. Students are presented with a patient case, starting with the chief complaint, then the history, physical and test findings. The info is provided in stages, just like an office or ER visit. In between bits of info, the students have to brain storm possible causes, eventually leading up to the point where they can start diagnosing diseases. Along the way they identify stuff they don't know and need to learn. Students meet in groups of 6-8, with two professors. One of the professors is a clinician, the other (me) is in a "basic science" field, our job is to keep the discussions within boundaries, help out (a little) when they are stalled, and act as an expert resource when asked. What we don't do is lecture to them. They do have some lecture courses, and some laboratory work in anatomy, histology, etc.

However, it was not always that way. We used to provide nearly all medical school content through lectures and labs. I attended those lectures nearly 30 years ago, and I used to teach them before the curriculum changed to the case-centered system we now use.

What does this have to do with Teddy's Rat Lab? Be patient, let me explain a bit more...

In those lectures there was always one or two students - we called them "gunners" (" 'gunning' for the top") and apparently the term is still in use - that tried their darnedest to be at the top of the class. Grades weren't enough. All of the students - and professors - needed to know that they were "the" top student in the class. In a sense, all of the med students are "gunners" compared to their undergraduate classmates, so you can just imagine what it takes to be thought a "Gunner" in a class of 108 others.

What this meant, is that in any lecture there would be questions. Questions are good, they show that the students are thinking, and they reveal what needs better attention in the lectures. However, out of every class, there was usually someone who would as THE IMPOSSIBLE QUESTION (or TIQ). Mind you, I like questions. I judged a classes interest on the students that came up after lecture with follow-up questions. Since I taught the basic neurophysiology of ion channels and action potentials, I got questions from chemistry and physics majors wanting more info, or history and music majors that needed more background info. But I dreaded TIQs.

Usually what happened was that a student had read something brand new in the New England Journal of Medicine and realized they had something that wouldn't be covered in a lecture that was based on material written 5 or more years ago. TIQs were verbal traps for the professors (not realizing that the NEJM article was likely based on 20 years of research with which the professor is familiar!). When a student asked a TIQ and it was answered with "I don't know," the student had scored, or "counted coup" on the professor. Obviously, if the professor couldn't answer it (and the student could) then the Gunner was smarter than the professor, right? The Gunners prided themselves on how many times they could score against the professors.

However, TIQs weren't necessarily impossible to answer, they just took time. See, med school lectures were 50 minutes long. I was allotted 4 lectures to cover 2 textbook chapters of material, giving mainly the highlights with the students required to read the rest for exams. If I was 30 minutes into a 50 minute lecture with at least 15 minutes worth of material left and was then asked a TIQ, I had a problem. So, what shoud I do?

Take 10-20 minutes to answer the TIQ, dropping the rest of the lecture and making the students read the rest (or squeeze it into the next lecture)?
Try to squeeze in a 5 minute version of the answer, confusing or boring the rest of the class?
Tell them to see me after class (but we only had about 7 minutes actual time between the lectures)?
Tell them to see me during office hours? (except I don't really have office hours, I don't have an office on that campus, and they would likely spend at least 40 minutes waiting and riding shuttles to get to my office).
Or say "I don't know" (or the more appropriate "That's too complicated to explain in the time allowed" - but the students would interpret it as not knowing the answer).

I had about 10 seconds to decide: #1 and #2 needlessly aggravated the whole class, #2 and #3 didn't provide sufficient time for a decent answer, #3 and #4 frustrated the ones asking the questions, and #5 made it look like the student was smarter than the prof. I generally opted for #3 and #4, because I could answer the question given enough time, but I know professors that used #5 on a regular basis.

Students asking a TIQ and getting response #4 or #5 generally considered it a win. Hey, they're back there virtually high-fiving each other. However, professors talk to each other. They kept track of who asked the most TIQs and if a particular student did so too often, they were "troublemakers." Asking questions is the path to knowledge; asking THE IMPOSSIBLE QUESTION (repeatedly) is not.

And you know, I can't help but think that Dr. House, M.D. asked TIQs when he was in med school.

Don't read this the wrong way. Questions are important! I like answering questions. Without questions, we don't learn. However, TIQs are counter productive. Just because you can think up an Impossible Question, doesn't mean you should ask it (or at least not in a public forum), nor does it really call into question the previous education, experience and writings of the professor.

They are amusing, though, when I look back at the patterns of TIQs and responses and compare them with the types of questions that students must ask if they are going to learn.Especially in today's curriculum where they have to ask questions, then go look them up themselves. Sometimes they must ask themselves the TIQs!

So, here's what it has to do with Teddy's Rat Lab blog...

The Aug. 8 blog discussed a number of the issues I have faced as a beta reader and scientific adviser to several friends and acquaintances who write science fiction. I gave several examples of the types of things I would advise against an author using in their story - including an example of XY chromosome-liked genetics.

Boy, did I ask for it! This blog is automatically posted on a bulletin board I frequent, and I often get questions and comments that show up only on that board. O that's when it started. I Certainly got questions - and in fact, I'll share some as Mailbag posts in the week to come.

Yes, I discovered that TIQs are not limited to Medical Students. They weren't exactly impossible to answer, and I'm more amused by the occurrence than upset at them being asked, but I had correspondents going out of their way to come up with obscure instances of genetic conditions that could meet the conditions that I had advised against writing. In my defense, I was trying not to be too specific about the author, novel, or specific passages within the novel. In their defense, they brought up some valid cases, but they were not common, and still did not invalidate my advice in the blog.

What I find amusing is that TIQs are apparently not limited to Medical Students, in fact they aren't really limited to science. Sometimes we *have* to ask TIQs. I suppose they are the consequence of inquisitive and curious people trying to gain a better understanding of what they've read. At the same time, though, I can't help but think that the ones asking the TIQs - much like Dr. House for the first 50 minutes of each show - are somehow missing the Big Picture.

Until next time - keep asking questions, they are the only way we "feed" our brains!

Monday AWESOME!

2011-08-22T14:29:00.000-07:00

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This week's Monday blog is less about the funny, and more about the awe-inspiring. THIS is the stuff that made me want to study science.

Back in the 70's, the Time-Life Science series of books combined incredible artwork with understandable explanations of everything from the atom to the workings of the brain. This combination of eye-catching visuals with science is a great way of catching nascent scientists - it certainly caught me. Now we live in a digital multimedia age - and illustrating science takes something that will appeal to the 3-D CGI audiences of today.

Biovisions, at Harvard University is working on just that.

http://multimedia.mcb.harvard.edu/

I cannot link the videos directly, but please follow the link, click the "X" at left to close the first page, then look at the videos in the middle of the page. At the top is The Mitochondria. Below that is The Inner Life of the Cell. Both are incredibly awesome animations that depict real-life cellular mechanisms. This is stuff that is *way* beyond Hollywood EPIC! [The only thing that would make it better would be an epic soundtrack - http://www.youtube.com/user/TwoStepsFromTheMusic#p/u/20/JNOpKwnAQyw.]

When done viewing the two clips, click on "The Inner Life Series" button at the left, then select the super speed version of Inner Life (lower left) for a narrated explanation of the scenes in the 'music video.' You can also go to the "All Media" link and view some other interesting video such as the Myosin video which illustrates the actin-myosin interactions underlying muscle contraction and intracellular transport.
This is neat stuff, and I can't wait to see what Biovisions produces next.

To continue both the concept of what makes scientists laugh - or cheer! - with getting back to regular blog posting, Wednesday's blog will feature "The Medical Student Syndrome" along with a peak at some of the strange and bizarre stories doctors hear from patients, then a few Mailbag blogs featuring the questions that readers have asked - or comments that deserve more than just a sentence of answer. We'll return to "The Lab Rats' Guide to the Brain next week - just in time for me to be gone a few days to Dragon*Con. I promise to build up some backlog and get back to a normal posting pattern.

Until next time. Treat your brain to some *AWESOME*!

Monday FUnnies (on Monday! this time)

2011-08-15T17:31:00.000-07:00

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Today's Monday Funnies focuses on the humor of Eric Schulman. The good doctor has written a number of humorous works that focus on the less than serious side of science.

For example - from: "How to write a scientific paper":

The real purpose of introductions, of course, is to cite your own work (e.g., Schulman et al. 1993a), the work of your advisor (e.g., Bregman, Schulman, & Tomisaka 1995), the work of your spouse (e.g., Cox, Schulman, & Bregman 1993), the work of a friend from college (e.g., Taylor, Morris, & Schulman 1993), or even the work of someone you've never met, as long as your name happens to be on the paper (e.g., Richmond et al. 1994).

and

You've written the paper, and now it's time to submit it to a scientific journal. The journal editor will pick the referee most likely to be offended by your paper, because then at least the referee will read it and get a report back within the lifetime of the editor. Referees who don't care one way or the other about a paper have a tendency to leave manuscripts under a growing pile of paper until the floor collapses, killing the 27 English graduate students who share the office below (Schulman, Cox, & Williams 1993).

Trust me - he's right on target! The full text can be found here: http://members.verizon.net/~vze3fs8i/air/airpaper.html - Note this was an actual paper published in the Annals of Improbable Research. [Formerly known as the Journal of Irreproducable Results until a bunch of lawyers got involved in science - a situation that should *never* be allowed!]

I highly recommend the "History of the Universe in 200 words" - especially once you see the result of running it through the automatic translation software: http://members.verizon.net/~vze3fs8i/air/histtrans.html

or "Gunga Dean":

...

Now in administration,
Where I had great frustration,
A-servin' to the needs of faculty...
Of all the suited crew,
The worst one that I knew
Was our Arts and Science leader, Gunga Dean.

... http://members.verizon.net/~vze3fs8i/air/gunga.html

The complete collection of Eric Schulman's science humor essays can be found at http://members.verizon.net/~vze3fs8i/air/index.html.

Enjoy, and exercise your brain - and funny bone!

Monday Funnies... on Wednesday

2011-08-10T17:00:00.000-07:00

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[Note this blog was delayed to allow the timely posting of Monday's blog.]

This week's Monday Funnies spotlights two different sites.

First up is Doc Nickel and his Website Doc's Machine, featuring "The Whiteboard" comic strip.

Granted, most of the jokes in The Whiteboard are engineering rather than strictly science, Doc and Roger are inventors, engineers, and accidental scientists. No one knows exactly where the character Doc (The Polar Bear) gets his funding, but his sources seem strangely familiar to me... Hmmm......

My favorite strips are... well, anything where Doc and Roger are inventing!

Inventing the wormhole gun: http://www.the-whiteboard.com/autowb174.html.

Doc discovers super-speed (in more ways than one): http://www.the-whiteboard.com/autotwb1053.html

----------

Next up, Dante Shepherd's "Surviving the World".

Dante does a great job poking fun at science and education/universities in general while also showing a bit of the serious side. In this entry, he has a bit of advice for making science a bit more interesting.

http://survivingtheworld.net/Lesson1133.html

Thanks, Dante, and in fact I think you and I are both working on that "better job of teaching science."

By the way - don't blame me if you waste a lot of time reading the webcomics, although some of my online friends to take pleasure in getting newcomers hooked on certain sites we find....

You have been warned!

Mwahahahahaha!

The care and feeding of Science advisors and beta readers...

2011-08-08T12:38:00.000-07:00

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I almost titled this "Betta" readers to play off of Sarah Hoyt's recent blog: http://accordingtohoyt.com/2011/08/08/you-beta-your-life/. Since this is a timely response to Ms. Hoyt, the Monday Funnies will appear on Wednesday this week. I think you may enjoy this column in its place, if not, come back Wednesday for your dose of funny science.

What I have learned as a Science Adviser / Beta Reader.

First - don't put us in the same aquarium (Oh, sorry, that's 'Bettas' again!) [with apologies to Sarah Hoyt.]

First - I have learned that every author wants something different from a beta reader, but they often want the same thing from a Science Adviser.

I have often heard or read despairing comments from readers that see early versions of a manuscript "Didn't the Author even *show* this turkey to Beta Readers? It's *full* of typos!" As Sarah Hoyt mentions in her blog, she doesn't want her beta readers to be copy editors - she wants them to advise her on the "readability," "likability", "believability" and overall sense of the manuscript. Their job is not to mark every typo or grammar error, but to tell the author when the plot has too many wholes, when a character is inconsistent, or the progression of events is not understandable. In this respect, the reader despairing of typos in an "Advance Readers Copy" is out of luck. Copy editing is not done at that stage.

However, they do have a valid point when it comes to science advising. The role of a science adviser *is* to pick up on the inconsistencies. Examples: (a) "Light years" as a measure of time; (b) space drives that produce 400 gravities of thrust in one section, and 4000 gravities in another; (c) males as "carriers" for an X-chromosome-linked disease that affects only women; (d) viruses treated with antibiotics. I have seen variations of these errors in many published books as well as manuscripts. [By the way - the answer to (c) is that if the disease was on the X chromosome, the male would not be a "carrier," he'd have the disease since he does not have a second X chromosome to carry a normal gene to counter the disease gene. For (d), antibiotics treat "biotic" infections - i.e. bacteria. Viruses are not "biotic."]

The science adviser is supposed to catch inconsistencies. What the science adviser is *not* expected to do is to change anything that would alter the essential plot or characters. Early in my tenure as an adviser to SF authors I had an exchange with an author that went something like this:

Me: "Hey __ - scientifically that's "an epithelial colonization with papules and pustules."
Author: "Speaker - my characters are grunts. To them its a bad rash with pus blisters. Now, if I need dialogue between the scientists who are *creating* the disease, I'll write it differently."

The story is more important than the science. That is not to say that accuracy is not important, after all, the hallmark of *good* SF is a good foundation in science, but there needs to be understanding that other parts of good SF include speculation beyond current capabilities, and above all, it has to be a good story.

Which brings me to Lesson Two that I learned as a beta reader and a science adviser: Make it understandable.

I know plenty of scientists that are excellent at what they do. They publish papers, get research grants, give seminars - but they can't explain what they do to someone without the same level of education that they received. A science advisor has to first explain the concept to the author, then be able to guide the process of getting the idea into the story. Note: you are *not* writing it for the author, you are helping them by saying "no, this is not consistent", "this doesn't read well", "this doesn't make sense." In addition, you can say "this is not accurate" and provide the appropriate information. It's not easy, and anyone that wants to try to position themselves as a science advisor needs to first *read* a lot of SF, then see how well they can explain their own work in SF terms.

SF authors *want* the reader to feel that the science is accurate enough to allow "willing suspension of disbelief." This is important to any form of SF, fantasy, speculative or adventure fiction. Readers are often willing to accept one (or two) unbelievable things if the rest of the science is accurate. For examples, I would draw your attention to Jack Campbell's "The Lost Fleet" series. There are two major "gotchas" in his Space Opera - first is the existence of a faster-than-light drive, second is ships maneuvering at significant fractions of light speed. Yet the rest of his space battles entail the slow ballistic trajectories of missiles and bombs dropped onto fixed outposts such as moons and planet-bound cities. Likewise, David Drake postulates a "sailing culture" for his RCN Lieutenant Leary books, yet he includes many realistic issues such as not having elevators on a spaceship due to various stress which would jam the elevator shafts.

It's a mix of the unbelievable, with science and engineering which is quite believable and understandable that aids the author in setting up the plot. It is the adviser's job to check the accuracy and understandability of the science to a much greater degree than that of a beta reader.

The third thing I have learned is to be careful in how you send your comments back to the author. Some authors prefer that you take the manuscript, mark your changes/comments in line, then send it back. To do so, you need a unique marker that the author can find using the search functions of their word processor. Authors I know use "###" or "///" for the purpose. Make sure you mark both the beginning and the end - and be careful to distinguish between corrections and comments. I once wrote a paragraph of side explanation to an author. I was surprised to find the complete paragraph in the final version of the book. I asked the author about it, saying "It was only meant as a comment for you." His response "Oh, I didn't realize. However, it fit, so I put it in." From this I learned that comments to the author - particularly long, involved ones - should be sent separately, so as not to confuse the poor author suffering from brain strain as they try to reconcile five sets of beta reader comments.

The most important thing I have learned as both a beta reader and science adviser is to find out what the author wants from you. Do they want "gobbledygook" and "handwavium" that they can use to give the impression of science to a particular scene? Do they want (allow) their scientist/engineer character to have a 500-word infodump to which the grunt characters can respond "Huh?" [Don't laugh, I know a best-selling author that allows his scientist co-author a single 500-word exposition per book!] Do they simply want the scientists to read a passage and comment on whether it "feels right?" It is very important for the scientists to not only have read other SF, but also that author's own works to get a feel for style and composition. Also, keep in mind that even if the author actually says "I need gobbledygook" they don't really mean nonsense such as "unobtanium" or "full-sprocket framistan with punctate lobes." No, what they usually want is science in terms that their readers will recognize as being realistic, without requiring a PhD to read it.

The down side of being a science adviser and beta reader is that when those other readers are saying "Why didn't somebody catch this mistake" they are talking about you. So it behooves the beta to look for the big issues, the ones that leap out of the page and hit you between the eyes. Perhaps the author will decide they don't matter, at which time it is best to leave it alone. But if you approach the task as recreational reading because "Wow, I get to read it *first*!" then you'll probably miss things that you would pay more attention to if you had a checklist from the author of items that they want you to review. On the hand, you *do* get to read it first, and sometimes that can make a difference to understanding how the author's mind, and the craft of writing actually work.

And when you're a neuroscientist that is interested in how the creative mind works, that can be more rewarding as seeing your name in the acknowledgments.

Fair warning...

2011-08-07T16:25:00.000-07:00

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Just to give y'all fair warning - my schedule has become very full over the past couple of weeks and I may need to take a break from the blog this week and/or next. Once the current block of teaching concludes in 3 weeks I'll have more time, but I plan to use this time to work ahead on the Guide and possibly get some other projects completed.

Monday Funnies will continue to post as scheduled, it's the Wed/Fri Guide posts that may have to be postponed. Rather than leave the blog blank I may look at some of the early posts or other material and see if it is worth editing and re-posting - or I may find some special content for filler.

Thanks for your understanding.

-Speaker

Ethanol, the Science behind the story...

2011-08-05T17:00:00.000-07:00

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In the prior blog I provided an example of alcohol effects on the brain in story form. Today I present the science behind that story, courtesy of Guest Blogger Karni Mata. K. Mata takes her name from the Goddess of Rats, or in her case, Goddess (mother) of Lab Rats, due to her position as a laboratory manager. K. has a doctorate in Psychology and works with me on several matters of interest to the readers of this blog. She was a bit too shy to come out here and introduce this blog herself, but believe me, she has very thoroughly researched the topic and is Teddy's Rat Lab's resident expert.

And now... the Science Behind The Story:

Alcohol. Ethanol.

It's a fuel, a disinfectant, an anesthetic, and a foodstuff.

The molecule ethanol - EtOH - consists of two carbon atoms, six hydrogen and one oxygen. It has the characteristics of both a hydrophilic (water-soluble) and hydrophobic (oil/lipid-soluble) compound and easily penetrates the skin, the mucous membrane lining of nose and mouth, the stomach lining, and distributes widely through the blood and body. A set of six enzymes - collectively called alcohol dehydrogenase - breaks it down, and the level of ethanol in the blood remains elevated until it is either broken down by this metabolic method (i.e. "metabolized") or it is excreted via sweat, breath and urine. The primary breakdown product of ethanol is "acetaldehyde" which is responsible for the headaches, upset stomach, and overall discomfort of a hangover. A further breakdown product of acetaldehyde makes "acetone" and "methyl ketone" which produce a sour taste, and are responsible for the bad breath and body odor of alcoholics and the chronically intoxicated.

The name - acetaldehyde - may seem familiar, especially if you have ever heard of the preservative "formaldehyde." In fact, acetaldyhyde is a 2-carbon structure, while formaldehyde has only one carbon. When a person drinks wood alcohol - methanol (ethanol is "grain alcohol") - the same alcohol dehygrogenase breaks down the single-carbon methanol molecule into the single-carbon formadehyde. There is a large amount of alcohol dehydrogenase in the retina of the eye. This is one reason why excess ethanol affects vision, and why drinking wood alcohol can cause blindness as the formaldehyde kills and "preserves" the sensitive neurons of the retina.

Alcohol affects multiple brain systems working overall as a central nervous system depressant. It may seem that alcohol stimulates a person since his or her speech becomes more animated and free, social inhibitions are reduced, and emotional responsivity is increased. However, it actually decreases the brain’s ability to function, resulting in cognitive effects such as hazy thinking and foggy memory, sensory effects such as dulled hearing and impaired vision, and physical effects such as weakened muscles and uncoordinated movement. Depression of self-control and judgment occurs as well, leading to poor reasoning and decision-making.

Within seconds of consumption, it alters the action of neurotransmitter systems. The neurotransmitter dopamine, involved in systems of reward, is initially increased causing euphoria. This feeling of pleasure can be accompanied by increased self-confidence and sociability. These dopamine surges in the brain sends signals that alcohol is important and valuable, and induce the brain to want more. High amounts of GABA neurotransmitters are released, increasing the action of inhibitory neurons, causing many systems to decrease activity, dulling the senses and pain and reaction time. Additionally, glutamate, an excitatory neurotransmitter, is less active, contributing to feelings of relaxation and sluggishness. A fourth neurotransmitter, serotonin, is increased in the presence of alcohol which may increase positive mood. It is also a neurotransmitter that when increased will raise the levels of dopamine and GABA, intensifying their effects.

As the limbic system, a group of several brain structures that work together is affected, emotions become more intense. Hypothalamus dysfunction can increase the intensity of feelings of attraction, or aggression, or sadness depending on the situation one is in. Sexual desire can increase, but the ability to perform sexually is decreased. Additionally, the amygdala is compromised, where emotional control, motivation, and interpretation of nonverbal emotional expression are processed. In the hippocampus, memory processes are also hampered. The thalamus relays information from the sensory organs to the cerebral cortex where they are processed into meaning. When this neural pathway is slowed down, the ability to respond quickly to information from the environment is slower and less accurate, resulting in longer reaction times which seriously hamper the ability to drive.

As blood alcohol rises, the frontal lobes are affected. This is where higher mental processes including thought, reasoning and decision making are largely processed. A dangerous consequence is that an intoxicated person may decide to drive even if he or she knows, when sober, that they should not.

As blood alcohol concentration levels increase in the cerebellum, fine motor coordination is reduced and speech is slurred. The ability to judge distances, and when to stop, is also impaired. The brain stem areas that control movement and balance are also affected resulting in a staggered gait and clumsiness. When blood alcohol levels become very high, the medulla in the brain stem, which regulates life support functions, becomes compromised. The body sends signals that poisoning is occurring, leading to vomiting (poison = toxin; someone drunk is “intoxicated”). Because inhibitory neural pathways are more active, swallowing, breathing and heart rate can also be affected, leading to unconsciousness and even death.

There are benefits from alcohol. The mild depressant action of just one or two drinks relieves stress and enhances mood. Many of the alcohol preparations, such as red wine, contain beneficial antioxidants. Ethanol does have some caloric content - it is produced as a partial breakdown of glucose. It is also used as a "solvent" to dissolve many medicines that would be poorly absorbed by the stomach and intestines. It also serves as a considerable "disinfectant" when added to water and food of questionable purity.

Still, as illustrated in the case of poor Joe from our last blog, it has its dangers as well. In comparison with other intoxicants - such as marijuana - Society as a whole has decided that the dangers of excessive ethanol consumption are acceptable. Only time will tell if Society makes the same decision about other intoxicants.

In the next blog we'll discuss some long-term consequences of ethanol use, as well as a discussion of problems strictly associated with (and indicative of) alcoholism.

Until then, take care of your brain - and if you take it out for a few drinks after work - do so with caution!
(and again - many thanks to K. Mata for today's blog!).

All Boozed Up...

2011-08-03T20:01:00.000-07:00

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16:55. BAC 0.00-0.01

"Hey, Joe! You coming with? Finally? We've been asking for a month. Me and the guys are headed to Harry's for wings and beer. You've put us off long enough, so you'd better show this time."

"Thanks, Buddy, I know I promised, but I can't stay long, I've got a date later."

"What? You? Mister all-work-no-play has a date?"

"Well, kind of a date, my brother's wife's sister's friend. They keep conspiring with my mother to get me married off."

"It's the grandkids, Joe, I keep tellin' ya - once ya give 'em grandkids they'll stop! Anyway, we're heading out in five. See ya at Harry's"

17:30. BAC 0.03

"Hey Harry! Another round! Joe, you need another bottle of... what *is* that stuff?"

"Hardcore IPA, Buddy, I like it, full body, nice rich taste. If you guys would stop drinking that horse piss you call 'light beer' you might find that you like a *real* beer!"

"Not for me, you might like those strong brewskis but I still gotta drive home to the wife. At least it finally got you out of the office and socializing with us for a change, so I guess I can't complain. Harry! Another bottle for Joey!"

17:50. BAC 0.07

"Damn, I'm gonna be late - I've got to catch the train and meet her at Le Bon Temps at 6:30. Let's see 10 minutes to walk to the station, catch the eighteen-hundred, 20 minute ride, another ten minutes to the restaurant. Yeah, I can do this, and the walk will do me good. Hey! Guys! See you on Monday!"

About this time, if you are as old as I am, you're probably expecting a narrator to pop up and say 'I am Joe's Liver' or something like that. Sorry to disappoint. Sure, I'm the narrator, but nothing quite so specific as to describe Joe and his liver on a night like this. No mistaking - it will be a night to remember, unfortunately, Joe won't remember it, or at least not remember *most* of it.

Joe is a typical guy in his 20's-30's. His weight borders on 200 pounds (90 kg). He spends all day in an office and doesn't exercise enough. He likes a beer or two in the evening. Socially he drinks wine, and occasionally something stronger. Tonight will be one of those nights. He's already had two beers: 11 oz bottles each, of a high-alcohol-content beer, and it is started to have an effect. He's socially relaxed, confident - too confident - and his judgment is starting to suffer. His blood alcohol content (BAC) is 0.07% - 0.07 grams of ethanol per milliliter (mL) of blood - and he's already over the legal limit to be able to drive in most countries (except U.S., Canada, U.K., Mexico). He *is* above the legal limit for Colorado. Luckily he doesn't live there and is using public transportation tonight.

18:30. BAC 0.06. Aldehyde 0.01

"Made it. Whew, I'm a bit sweaty, ugh, need some deodorant or something. Good, the vending machine has that spray cologne. Where is she? It was six-thirty, right? Bartender! Gin-and-tonic, with lime. Thanks."

Forty minutes after he finished that second beer, Joe's BAC has dropped by 0.01%. If he stops now, the alcohol dehydrogenase in his body will convert the rest of the alcohol in his blood to acetaldehyde in another 4 hours. If he sleeps for about 4-6 hrs after that, the aldehyde will be cleared from his bloodstream as well (0.01% per hour) and he probably won't notice any lasting effects in the morning other than strong body odor from the aldehyde in sweat.

He's still not noticing much of an effect of the alcohol because at 200 pounds, but 5 feet 10 inches in height, Joe has enough fat in his body to "buffer" some of the alcohol before it reaches his brain. Unfortunately, he skipped lunch and has no food in his stomach except 1 chicken wing and a handful of snack mix.

18:45. BAC 0.08. Aldehyde 0.01

"Damn, she's still not here. Did I get the time wrong? Bartender! I'll take another, easy on the tonic this time around! Oh - and another bowl of bar-mix, I had a meeting at lunchtime and my date is late."

Joe has consumed two beers, one gin-and-tonic and is working on a second. That would ordinarily constitute 4 standard doses of alcohol. The stand measurement for alcohol consumption is one shot (1.5 oz, 44 mL) of liquor - 80 proof (40% alcohol by volume) - or 5 ounces (148 mL) of wine (9-15% alcohol by volume) - or one 12 ounce (355 mL) can of beer (4-6% alcohol by volume) . However, these are 'standard' measures, and vary with the actual alcohol content. Joe's 'Hardcore IPA', for example was 9% ethanol-by-volume and two bottles gave him at least three 'standard doses' of ethanol - it's a good thing he didn't order 'Tactical Nuclear Penguin' (32% alcohol - the equivalent of about 6 beers).

18:55. BAC 0.10. Aldehyde 0.02

"Bartender, ano- Oh! Hello! You're must be Tracey, right? Cheryl told me a lot about you!... No, I haven't been waiting long. Wow, she didn't tell me how pretty you were. I think I'm in love already! Bartender, get the lady whatever she wants. Sure, I'll take one to the table."

19:06. BAC 0.11. Aldehyde 0.02

"Would you like some wine? They have this lovely Australian Syrah... Bordeaux? Sure. let's see, hmm, the lighting is sure low, either that or I'm going to need to borrow your glasses ... Yes, sir, the 1998 Bordeau. Oh, sorry about knocking over the salt - just a pinch over... what was that old superst... uh. legend? A pinch of salt over the left shoulder? Yeah. That's it."

Joe is legally intoxicated in any jurisdiction by this time. His vision is just a bit blurry, his coordination a bit off, and he is making - and correcting - small slips of the tongue and memory. He hides it well, having had a bit of practice in college, but he hasn't drunk this much in several years. At his current Blood Alcohol Concentration, it will take over 7 hours to clear the ethanol from his bloodstream and more than 11 hours to metabolize the aldehydes. We *will* have a hangover in the morning.

20:33. BAC 0.18. Aldehyde 0.04

"What the hell, Jake! No one told me she was a Vegan! How was I to know she'd get sick at the sight of Steak Tartare? Then she stuck me with that damned Bordeaux. I hate French wines! ... What do you mean what did I expect in a French restaurant? Up yours, Buster! Oh, sorry, Lady, and I am *not* drunk! ... 'nother sh-sh-sh-shot of Jack, Jake. Hah! Jack-Jake! Thass funny, that is! Yeah, 'nother Jake-Jack and make it a double!"

Joe is now in trouble. Two strong beers, two-and-a-half gin-and-tonics, three glasses of wine and at least one shot of whiskey has raised his BAC to levels that are clearly affecting motor control, judgment, speech, and vision. If he tries to stand he will discover that the high concentration of alcohol in his blood has actually allowed ethanol to enter the cerebrospinal fluid and the fluid of the inner ear, increasing the effects on the brain as well as directly affecting balance (by suppressing hair cells in the semicircular canals), blood pressure, heart rate, etc.

If he stops now, he'll have a miserable morning, but will have detoxified by the afternoon. Unfortunately the night is not yet over...

21:57. BAC 0.22. Aldehyde 0.06

"Hoo-ey, that's good stuff! You say your brother makes it up in the mountains? Wow, never had it before! Sure glad you came along, sweetie, the nerve of that guy, cutting me off! I'm going to call his b-b-b-boss in the... the... wassname... yeah! mornin' Yeah, wha' kinda beertender does he think he is? Oops, sorry darlin, din' mean ta trip ya. Hoo. You shore are purty, darlin'! Wheah? Ah'm fum Tay-has, din' ah tell y'all tha'?"

Joe's BAC is now in the dangerous levels. If he keeps drinking, he will lose consciousness, lose memory, lose his bladder function and if he ends up in a position in which it is hard to breathe, he could suffocate. He does not understand his own actions, or what is wrong with his behavior. He may find himself attracted to his 'Darling' but will likely be unable to do anything about it. To say that his judgment is impaired is too mild. At this point, Joe has no judgment -after all, he just drank the 2 shots of moonshine (70% alcohol - the equivalent of 3-4 standard drinks).

"Wha's tha' you say, Darlin'? Your place? Wha' Ah thought we *were* at yore place?"

23:59. BAC 0.28. Aldehyde 0.09

[snoring...]

Joe has lost consciousness. When he awakens he will still be highly intoxicated. He will also have The Mother of All Hangovers. He will have no memory of the evening after the failed dinner date. He will remember only that it went badly, but not why. He will not know where he is, how he got there, or what he has done. That may be rather fortunate for him.

07:30. BAC 0.17. Aldehyde 0.13

"Damn! Too loud! Stop that noise! Ohhhhhh, my head! What? Where am I? What happened?....
....

"Oh no!"

------ On Friday, "The Science Behind the Story"

Monday Funnies

2011-08-01T14:07:00.000-07:00

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The Hungarian biochemist Albert Szent-Gyorgyi won the Nobel Prize for Medicine in 1937. His research focussed on Vitamin C. We once defined a vitamin as: "A substance that makes you ill if you don't eat it!"

A couple of my favorite (paraphrased) Szent-Gyorgyi quips are:

"Under the most precise conditions of environmental and behavioral control - the lab animal does what it damn-well pleases!"

"A drug is that substance, which when injected into an animal, produces a research paper."

Truer words were never sp- ..., well, paraphrased.

Today's Monday Funnies is about humorous quotes about science.

SciScoop (http://www.sciscoop.com/science-quotes), lists a page of science jokes and quips, but I didn't find them to be particularly scientific - more commentary and less humorous. Basic Funny Jokes (http://www.basicjokes.com/dquotes.php?cid=16) is a bit more on-topic. There is also a list organized by topic at: http://jcdverha.home.xs4all.nl/scijokes/quote.html

My favorites:

"We can lick gravity, but sometimes the paperwork is overwhelming." - Wehrner von Braun

"When a distinguished but elderly scientist states that something is possible, he is almost certainly right. When he states that something is impossible, he is very probably wrong." - Arthur C. Clarke

"The essence of life is statistical improbability on a colossal scale." - Richard Dawkins

"Basic research is like shooting an arrow into the air and, where it lands,
painting a target." - Homer Burton Adkins

"The most exciting phrase to hear in science, the one that heralds new
discoveries, is not 'Eureka!' but rather 'hmm....that's funny...' " - Isaac Asimov

"Your theory is crazy...but it's not crazy enough to be true." - Neils Bohr

There are many more out there, and as time is short - I challenge you to find them. My apologies for irregularities in the posting schedule, but I am teaching for the next six weeks,therefore a good portion of my daily work has shifted to work in the evenings, at home. This has somewhat limited the time available for blogging. I promise to stick to the main schedule as much as possible, and to work on that backlog of comments on last week's blog posts.

I leave you with this final (humorous) thought: "I know that this defies the law of gravity, but, you see, I never studied law." - Bugs Bunny

Medical Marijuana

2011-07-28T17:00:00.000-07:00

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[I have reprinted a response to a recent article and online debate.]

It happens every six months or so, a news article picks up on a new miraculous cure involving marijuana and I start this argument all over again. On one side is usually a group advocating legalization using medical marijuana as justification. On the other side are strict traditionalists claiming that there are no medicinal benefits, and the legalizers just want an excuse to smoke pot. So where does that leave the scientists and doctors who are actually doing research into the medicinal applications of cannabinoids (the chemical ingredients of the cannabis sativa marijuana plant)?

Well, usually in the middle. And as is true in so many cases, the efforts to identify and bring to practice real medicinal uses are hurt by both sides.

First and foremost, I am not arguing for or against legalization. I really don't care that much what substances you put into your body. Legalization is a question to be decided by a society that debates and votes for their respective stand on the issue. As a researcher of cannabinoids I have a stake only in potential medicinal applications – but also in the use and mis-use of the concept of medical marijuana.

I do not find marijuana to be harmless. There are side-effects. Cannabinoids alter memory, they alter the ability to make critical decisions, in some cases they can affect reaction time, and smoking the unprocessed, unfiltered leaf exposes the lungs to more chemicals than tobacco. It can reveal latent tendency to anxiety, depression or schizophrenia. It is up to society to decide if those side-effects are less than, say, ethanol. This is why I stay out of the legalization argument.

Where I do argue is against the use of "marijuana" as a medicinal agent. There are very few medical applications where smoking marijuana is an appropriate means of delivering appropriate cannabinoids to the body. One of those is cancer pain – by all means, if the marijuana alleviates pain and allows the patient to escape for a few hours, do it.

But there are many other medicinal applications: glaucoma, nausea, loss of appetite due to chemotherapy, bone pain, convulsions, stress, cancer, and now… autism (http://www.ksdk.com/news/article/267091/9/Using-medical-marijuana-to-treat-autism). The recent autism reports are disturbing because there is no research supporting the results, and the probable mechanisms would likely be from compounds other than the widely known ingredients of marijuana. The problem is that so many of these medicinal applications do not rely on the same chemical compounds of marijuana smoke. Smoking marijuana bought from a street vendor – whether a medicinal storefront in Berkeley or a street pusher in Detroit – provides no control over the chemical constituents of marijuana.

Does that matter? In a word – yes. The chemical compounds mean everything with respect to effects. You've probably heard of Tetrahydrocannabinol – THC – the main ingredient of marijuana. But did you know that there is more than one type of THC? There's Delta-9-THC. That's the one usually referred to with marijuana, but there's also Delta-8-THC and 11-hydroxy-THC. Those are slightly different chemical compounds, and have slightly different potencies. How about Cannabidiol? Ever hear of it? Cannabidiol is responsible for some of the anticonvulsive and anti-anxiety effects of marijuana. How about Cannabigerol, Cannabidivarin or Tetrahydrocannabivarin? These are all trace ingredients on the average in the cannabis sativa plant. New research shows that these compounds have some very important medicinal effects – as well as potential side effects depending on what is being treated.

And here's the dirty little secret of medical marijuana – when buying street pot, you don't know how much of these other chemicals are in the plant. Pot is grown – even bred like roses and show dogs – for a particular characteristic, the euphoric feeling or "high." Cannabindiol for one, and some of the other cannabinoids block or reduce that high. About one third of all pot available in the U.S. has negligible Cannabidiol. Now if you were counting on that "medicinal" effect, you're out of luck!

The concept of buying pot from any source and self-medicating is not medicine – it's smoking pot. Pot smoking is not medicinal. If you go to the doctor with severe pain, he doesn't prescribe chewing tree bark (for salicylate, the main ingredient in aspirin), boiling poppies (for opium and its primary product, morphine) or eating mushrooms (for muscarine, and it's derivative acetylcholine). No, the doctor prescribes a controlled dose of a drug that is a purified chemical derived from or synthesized to resemble a single ingredient in those substances. Again, medical marijuana, as practiced in this manner is not medicinal.

I once had this argument online in a discussion group and my opponent started listing research studies that proved the medicinal benefits of marijuana. Yes, there are studies that support medicinal applications. However, my favorite was an article that showed suppression of lymphoma growth: Marijuana Cures Cancer! Unfortunately not true. The discussion stopped cold when I pointed out that the substance used in the test was a synthetic chemical (first identified in Israel where they do a lot of medicinal cannabinoids research) and was not present in the cannabis plant and therefore could never be obtained by medical pot smoking!

At the recent meeting of the International Cannabinoid Research Society – a group of about 400 scientists and physicians that study cannabis and cannabinoids from drug abuse to medicinal potential – less than 10% of the scientific presentations used smoked marijuana – and most of those were abuse studies. The truly medicinal studies used purified extracts and synthetic compounds. Here's a hint: if an article refers to THC it is probably talking about marijuana leaf or at least a purified extract; if it mentions cannabidiol (CBD) is definitely a purified extract; if it mentions chemical designations such as WIN 55212-2, CP55940, HU-210, anandamide, 2-AG, it is talking about synthetic compounds not found in marijuana.

In summary, I really don't have much of a stand on marijuana legalization, but I oppose medical marijuana use as it is currently practiced in this country. Why? Because it is not medicinal. It is becoming more obvious that there are many medicinal benefits to be had from a better study of the cannabinoid chemicals in cannabis. Those benefits are all too easily confused by those who promote use of a drug in the absence of controlled dosing, known chemical composition and physician monitoring. To argue otherwise is contrary to decades of scientific research attempting to understand those medical applications.

Smoke pot, or not. Just leave so-called "medical" pot smoking out of the debate.

[Dr. Tedd "Speaker to Lab Animals" Roberts is a neuroscientist with 29 years research experience studying effects of drugs on learning, memory and cognitive decision making in animals and humans.]

early posts

2011-07-26T20:04:00.001-07:00

Post scheduling glitched and you got the whole week yesterday and today. Very hard to undo, so, enjoy the week, just read one at a time!

Curious things we learned from epilepsy surgery...

2011-07-26T18:44:00.000-07:00

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In the previous series of blogs from The LabRats Guide to the Brain,I mentioned that many surgical treatments have been used to remove the neural tissue that acts as a site of origin for epileptic seizures. One of the pioneers of this work was Dr. Wilder Penfield, who has been mentioned in this blog in the past (click on the content tags for previous blogs). Penfield's medical research involved identifying the point of origin for epileptic activity, then surgically removing that piece of the brain. Before the surgery, however, Penfield and colleagues need to find out what function is served by that area of brain. Very low voltage/amperage electrical stimulation was delivered via hair-thin stimulating electrodes. Clearly some stimulations caused physical body movement, and unfortunately some triggered the very epileptic activity being treated. But some of the other results were astounding: patients described sensations, feelings or complete memories. These studies gave rise to much of the mapping that we know today - including that of the motor and sensory homunculi are courtesy of such recordings as preparation for epilepsy surgery.

Another striking result of epilepsy surgery was the case of patient H.M., very well known to neurosurgery and neuroscience students alike. H.M.s epilepsy originated in the hippocampus, an area near and dear to my... memory. Yes, the hippocampus is the structure most associated with processing of new memories. On September 1, 1953, neurosurgeon William Beecher Scoville removed part of the medial Temporal Lobe on both sides of H.M.'s brain. From that point onward, his ability to form new memories was impaired, although his ability to learns skills and remember past events appeared unaffected. The surgery removed most of the hippocampus, amygdala and entorhinal cortex, thus removing a critical link in the brain circuitry necessary for processing memory. H.M. died in 2008, and for 55 years he became the most studied patient in Neuroscience!

Another strange but true tale involves the split-brain. Epileptic seizures can originate in a small area of brain and eventually spread to involve major portions of both hemispheres. As a last-chance attempt to halt the progress to the opposite hemisphere and limit the duration and extent of seizure, a procedure called corpus callosotomy is performed to cut the connections between hemispheres of the brain. The resulting separation resulted in much of what we now understand to be the lateralization of functions to two different halves of the brain. However, it is the behavior of the "split-brain" patients that is most curious. As discussed in the sections on vision, each retina projects the left half of the visual field to the right brain, and the right half of the field to the left brain. Without an intact corpus callosum connecting the two hemispheres, the patient cannot put both halves of the visual field together. As a result, they constantly scan their eyes back and forth and move their head to allow both halves of the brain to "see" the entire field. Split-brain patients have been observed to be in conflict between intended actions controlled by the separate halves of the brain - expressed as one handing restraining or slapping the other, or two hands attempting to do the same task.

Fortunately these drastic surgeries not performed with much frequency, rather medication and more precise surgical techniques suffice for most epilepsy patients. Still, drastic cases exist, and parts of the brain may need to be removed. The resulting responses, deficits, and conflicts are very important to our understanding of the brain!

Until next time - take care of your brain - you don't want to lose it!

Monday Funnies

2011-07-25T17:00:00.000-07:00

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Today we have a two-fer:

Sidney Harris has been drawing cartoons that poke fun at - and point out the limitations of - sceince for a long time. Sidney's work shows up in all of the science labs sooner or later - in fact, his work is about on par with Gary Larson's The Far Side* in terms of showing up on lab doors, walls, offices, etc.

Today's link is to a comic which tickles my funny bone since it actually hits pretty close to home. When you train a lab rat to perform a particular test, it will get better at that test. Then you have to come up with a harder test. Pretty soon the rat gets good at that test...

Today's Monday Funnies link:

http://www.sciencecartoonsplus.com/gallery/biology/galbio2b.php#

Be sure to go back to the home page and check out more of Sidney Harris' cartoons.

*Now for that Two-fer.

Here's one of those Far Side cartoons that I have seen in many labs:

Anyone who has ever worked with old equipment in a lab has probably felt like they were working with one of these "early microscopes." I had one about 20 years ago that looked pretty much the same. Of course it was already 20 years old by that time.

I have noticed that labs that do not have the latest and best equipment and devices - that have to scrimp and save and do their own maintenance - tend to have this cartoon up somewhere.

Been there, done that.

And for the sake of official copyright, I found this image on the web, linked and copied many times, but Gary Larson and his publisher own all rights to the image. I am just passing it along for the humor value.

As a final note, I'd like to provide a link to this outrageous article: http://www.dailymail.co.uk/news/article-2017818/Embryos-involving-genes-animals-mixed-humans-produced-secretively-past-years.html.

Why am I linking it here? Because in fact it is funny. Any scientist reading the article will realize that the content of the article is distorted, even falsified. The coincidence of the article appearing on the eve of the premiere of "Rise of the Planet of the Apes" movie is ... too good to be true.

Why am I laughing? Because people - especially the press - are gullible. Because I know a few things about how the science is conducted. At present "human-animal hybrids" are not viable. Yes, scientists are looking at genes by inserting a single gene structure into a frog egg or mouse and studying the gene for a better understanding of human disease and medication. At present there is no way to put "animal genes" into humans - after all, where are they getting the embryos? Three universities are named, but not the labs, the people or the specific projects - and that's just not like the historical actions of "whistleblowers" and activists that bring unsafe and dangerous research to light. Someone, somewhere, is laughing at the prank they've pulled on us all.

Be good, be safe, be informed, but above all, learn to laugh.

Introducing the LabRats

2011-07-24T16:32:00.000-07:00

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The LabRat Adventures

It was a raining when the stranger entered the Diner.

“You mean it was a Dark and Stormy Night?”

No. I mean that it was raining. It was daytime, and the rain was warm and gentle. It was a good thing, too, or the stranger would have looked like a ‘drowned rat’.

His fur was black from his head to just above his tail. There was a small patch of white at his throat and at the end of each forepaw. His belly and hind legs were white, giving the impression that he was wearing a tuxedo and tails. “Scoo-bee-doo-bee-doo, bee-doo-bee-doo-bee” he sang quietly as he looked around.

A small black furred head looked out from the back booth. Soon others peaked out from under other booths and one even looked out from the window into the kitchen. The first rat made his way up the the stranger and introduced himself. “I’m Ratley, manager of LabRats, Inc. and supervisor of this crew. What can we do for you, Sir?”

“M’name’s Dean, my good fellow. I seem to have misplaced my Pack and thought I’d stop in for a cuppa Joe.” He looked around at the other rats. "Any chance of that,Sir?"

"Sure" said the large rat. He raised his voice and called back to the kitchen: "Ratso, cup of coffee for the customer!" Turning back, he saw that the newcomer was looking around at the other rats. His gaze lingered on two under the jukebox. "That's YouDirtyRat imitating a dust bunny and Nestor is the one tangled in the electrical cord. Ratso helps out in the kitchen and handles supplies. Ratface is the one chasing his tail and Ratfink is off somewhere up to no good. We're the cleaning and maintenance crew for this Diner. We've also been known to help out with serving."

"And the humans? They *allow* this?" the newcomer asked.

"Sure, ever since Speaker to Lab Animals found us we've been helping out here. The people are nice if a bit strange and we get all the scraps we want. Speaker's that great big human in the booth. He thinks says he's a scientist or something, but he lets us get away from the lab for a bit each day.

"So, what lab are you from, and what experiments have you participated in?" asked Ratley.

"Well, that's a long story" said Dean.

"That's okay, we've got time. It will take the lads a while to carry that cup of coffee all the way out here…"

[to be continued next week in "Life in the Lab"]

Seizures and Epilepsy

2011-07-22T17:00:00.000-07:00

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So, what constitutes or causes a seizure?

To explain, let me back up and describe normal activity in the brain: Individual neurons respond to a stimulus by creating an electrical current called an "action potential." This current is caused by a rapid movement of positively charged sodium ions into the neuron from the fluid surrounding it. This electrical activity - called a "spike" or "unit discharge" when speaking of assemblies of neurons - is the essential information carrying actviity of a neuron.

Normally when a neuron generates a spike, neighboring neurons are quiet. This is because a combination of neural connections and neurotransmitter chemmicals at those connections act to block the spikes generated by the nearest neurons. This ensures that the neuron is responding to its own inputs, and not that of its neighbors. It also keeps the representation of information "sparse" to allow a lot of *diifferent* information to be represented.

If the inhibitory connections (using the neurotransmitter GABA - gamma aminobutyric acid) are too weak, the activity of a given neuron can influence or even spread to its neighbors. If the inhibition is too strong, the activity tends to "bounce" or oscillate between active (not inhibited) and inactive (inhibited) states. Either instance can cause neurons within a region to begin firing spikes that are synchronized - all firing at the same time.

This is the essence of a seizure. If the synchronous activity is limited to just a small area, it is termed a "focal seizure" and the patient may experience nothing more than a slight muscle twitch, speech disturbance, visual disturbance, etc. If the synchronous activity spreads, the patient experiences a "generalized seizure" with convulsions and even loss of consciousness. The initial synchronous activity can mimic sensory inputs and cause the patient to "see", "hear" or "smell" something unusual. This "aura" commonly signals to the patient that a seizure is imminent, since it precedes the generalization of seizure activity that leads to convulsions.

If the seizure originates in prefrontal or limbic (hippocampal) regions and does not spread to motor cortex, the patient experiences an altered state of consciousness where they are unaware of and unresponsive to their surroundings - but without convulsions. This is called an "absence" seizure, and can be rather difficult to treat because the symptoms can be easy to miss. Absence seizures are more common in children and youth than in adults; they usually last for less than a minute, and are typically not preceeded by an aura.

Following a seizure, neurons act like any other cells of the body that have had an extreme workout - i.e. they are fatigued. Doctors call the period of a seizure the "ictal phase" and the lethargy, dullness and depression that follows a seizure the "post-ictal phase." In many patients the siezure itself may be undetected (lasting <2 min), and only the post-ictal phase (lasting tens of minutes) is observed.

In many ways, brief focal seizures and TIAs can have similar effects - a transient disruption of brain function that passes in minutes. A key difference is that seizures will tend to always occur in the same part of brain, and the "aura" with seizure onset allows the patient to always predict when an event will occur. Critical to diagnosing the difference between a vascular event and a seizure is the EEG. TIAs and strokes are characterized by a reduction in neural activity while seizures demonstrate an increase and a synchronization simuilar to the EEG shown in the previous blog.

What then, constitutes epilepsy? Is an convulsion or seizure reason to worry about a diagnosis of epilepsy with all of the attendant social issues (fear of seizure in public, loss of driving privileges, etc.)?

No. As mentioned last blog, convulsions can be caused by fever or head trauma and never recur once the fever is lowered or the trauma is treated. Focal seizures without loss of consciousness - especially if preceded by an aura - need not occur with sufficient regularity to warrant medication or treatment. However, recurrent seizure, with altered consciousness, and impairment of thinking, vision, hearing or movement following a seizure *is* epilepsy. Like so many other brain disorders, it represents a continuum from mild seizure to severe, full-body conculsion that can lead to serious injury.

Epilepsy is diagnosed primarily by recorded the EEG from multiple sites on the skull during a seizure. Synchronous firing of neurons in wide areas of the brain signifies an epileptic seizure, and is considered "proof" of diagnosis. Causes of the disease vary, but the consensus is that the "focus" of a seizure (its point of origin) is a region of brain that is predisposed to fire synchronously. Neurologists call this an "irritable" focus, and may indicate that the normal recurrent inhibitory connections which prevent synchronous firing are damaged. As stated before, an irritable focus may result from injury, stroke or disease, and can sometimes be detected on MRI or CT scan.

Treatment of epilpesy and mild seizure disorders is usally via medications that can prevent synchronous firing from developing. Since the medication targets unusual activity, it typically doesn't alter the patients sense of their own brain activity, but if high dosages are required, the patient can feel dull, listless, lethargic or have "fuzzy thinking." Neurologists and pharmacologist have attempted to develop drugs to treat seizures via manipulations of GAB neurotransmitter, but have not been as successful as with other systems. The GABA drugs *do* make good medications for intractable nerve pain, however. If the seizures cannot be controlled with medication, but the "irritable focus" can be accurately identified, it is possible to perform neurosurgery to remove that brain area and stop the initiation of seizures.

The results of such surgeries have been... interesting... to say the least.

Since this blog is now running quite long - I'll stop here and resume next time with "curious things we learned from epilepsy surgery" which should provide plenty of inspiration for the imaginations authors and readers alike!

Stay tuned for LabRat Adventures this weekend and Monday Funnies next week.

All seized up..

2011-07-20T20:18:00.000-07:00

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To follow up on the discussion of stroke and TIA (transient ischemic attacks)... Repeated ischemia can leave scar tissue that is prone to unpredictable electrical activity. The irony is that such unpredictable activity is in fact quite ... synchronized. The EEG traces at right show the random, irregular pattern of normal brain activity at first, then large, synchronous pattern of seizure activity for 5-10 seconds, and a return to normal EEG.

So - what is a seizure?

Most people, upon hearing the term, think of convulsions and epilepsy. However, seizures do not have to involve convulsions, and not all seizures or convulsions indicate epilepsy.

Definitions: A seizure is an episode of periodic, synchronous activity in brain cells that normally do not fire synchronously. A convulsion results from a seizure that involves the motor cortex, resulting in muscle twitches or spasm. Epilepsy is a disease of recurrent seizures - with or without convulsions - that originate in the same area of brain.

Seizures can be one-time events or recurrent - even without a diagnosis or epilepsy. They can be caused by scar tissue from stroke or TIA, from head injury, vascular irregularities, congenital defect or none of the above. Convulsions can result from seizure, infection or fever - anything that causes the motor cortex to fire the neurons out of sequence. A diagnosis of epilepsy generally only comes once seizures are diagnosed as recurring uncontrollably, do not respond to baseline medications, and involve an altered state of consciousness. In this manner, tics, spasms, tinnitis and optic flashes are all forms of seizure (if they originate in the brain) with no stigma of epilepsy involved.

Convulsions come in many different types - the petit mal seizure evokes hardly any muscle twitch, while the grand mal can involve muscle spasm throughout the whole body. Partial seizures may involve a single limb - right hand and arm up to the elbow, for example - or perhaps part of the face. Complex seizures progress from one area of the brain to another - thus producing a "march" of convulsions until they involve the whole body. [A "complex-partial" seizure starts as a partial seizure - generally involving a single limb, then progresses to whole body convulsion.]

The next blog will complete the discussion by exploring the various forms of epilepsy, with discussion about medication, diagnosis and the lifestyle impacts of seizures.

Monday Funnies

2011-07-18T19:22:00.000-07:00

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After much consideration of the amount of time I had available to prepare blogs, as well as what direction I wished to take this blog when The Guide is finished, I have decided to change up the posting schedule. I had the great good fortune to attend LibertyCon this past weekend in Chattanooga this past weekend. I participated on Science panels, spoke at length with many authors, and with the inestimable Pete Abrams, creator of the long-running "Sluggy Freelance" webcomic (http://www.sluggy.com). Among other things we spoke of science and webcomics. It occurred to me that this blog would be a good place to link to stuff that makes me laugh - as a Scientist!

The Classic example of Science Humor is the sadly no-longer-drawn Far Side comic. Gary Larson just had a way of poking fun at Science and Scientists while still capturing the essence of what makes us tick. It is still around in calendars, web links and taped to walls of student cubicles and academic offices!

For today, I'd like to link to PhD Comics. "Piled Higher and Deeper" is a phrase quite often used to describe the futility and absurdity of advanced degrees. Jorge Cham's main characters suffer many of the indignities that we all faced in grad school - the distant professor, the unappreciative undergrads, and misunderstanding public. One of my favorite comics describes the "Science News Cycle" (link below) that shows how a grad student's statistical correlation turns into sensational news. Many of us have been there. We have a love/hate relationship with the press and the public. Everyone *needs* to know what we discover, but few of us can have the expository genius of an Isaac Asimov or a Carl Sagan - or even a Jorge Cham.

It's funny - to us at least. I hope it's funny to you as well!

So - for the inaugural "Monday Funnies"

http://www.phdcomics.com/comics.php?f=1174

Enjoy (and don't blame *me* if you lose sleep reading the archives!)

TIA - the "temporary stroke"

2011-07-16T17:00:00.000-07:00

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This is part two of a four-part series on the interrelated subjects of stroke, TIA, seizures and epilepsy.

In the previous blog, I spoke of strokes - cerebral infarctions which are analogous to the myocardial infarction of the heart (heart attack). Just as the heart has symptoms of angina from temporary interruption of blood flow, so does the brain have TIAs - transient ischemic attacks. TIAs are essentially miniature strokes,without the long-lasting obvious effects of a stroke.

TIAs can result from three factors - (A) low blood-pressure-induced lack of blood flow to the brain, (B) spasm of the blood vessels interrupting blood flow to the brain, (C) breakaway clots that temporarily block blood vessels in the brain. The key feature of all is that they are transient. TYpe A requires two factors - a malformation of blood vessels in the brain that cause the blood flow to be decreased under normal conditions, and an event that further reduces blood flow. The former can be caused by previous blockage, arterial plaques (i.e. atherosclerosis), scar tissue, or malformed vessels. The hypotensive or low whole-body blood flow event can be caused by rapid posture change (usually standing up), using the bathroom (especially if constipated), or medications to lower blood pressure. One example of TIA is thus a person suddenly standing up, getting dizzy, feeling pain, and losing consciousness.

An important issue about blood pressure is that there are two pressure states - the highest pressure is encountered as the heart is actively pushing blood into the highly elastic arteries at the peak of the heart beat. As the heart rests and refills, the pressure in the blood vessels is largely a function of the elasticity of the vessels and smooth muscles lining the vessels which can constrict the diameter and regulate the blood pressure. Thus the high pressure is the result of the heart's ability to pump, and the low pressure is a result of the rest of the circulatory system regulating the pressure via blood vessel size. This minimum pressure is import for being able to force blood through the smallest vessels (capillaries) that provide the actual exchange of oxygen, carbon dioxide, glucose and metabolic wastes at the cells themselves. If there is a partial blockage anywhere, or an area that restricts the blood flow for only a short space, the area downstream will have lower blood pressure and less "perfusion" of blood through the capillaries.

Thus if the whole body blood pressure drops - such as when a person on heart and blood pressure medication stands up suddenly - the pressure downstream from a partial blockage may be too low to perfuse a particular brain area. The neurons are temporarily deprived of oxygen - i.e. transient ischemia - and for a very brief time the patient has symptoms of a stroke - albeit a small one.

A similar temporary occlusions can result from spasm of the smooth muscle fibers that regulate the size of blood vessels. Spasm can be due to drugs or medications, stress, environmental conditions or seizure-like activity (see the next blog!). A vasospasm is also likely to occur if there is an unusual shape or configuration or even damage to blood vessels in the brain. The source can be congenital or due to head injury or even prior strokes.

The final cause is from mobile clots or debris in the blood. The technical term is "emboli" and typical sources include clots due to a damaged heart valve, traumatic injury with extensive bleeding (and subsequent clotting) or peripheral artery disease in which clots form in the legs of patients who have been immobile for too long. Emboli will travel through the blood until they are either broken apart or reach a blood vessel narrower than the clot. If the clot reaches the brain, but once lodged in a vessel it breaks down further, a TIA results. If the clot cannot be dislodged or more clots build up, a stroke results.

TIAs resulting from blood pressure drops or vasospasm may occur anywhere in the brain, but will most likely involve the same area each time if there is a malformed or partially occluded blood vessel that is sensitive to low perfusion. TIAs due to emboli will most likely be different each time since the eventual destination of the clots will vary with each instance.

TIA symptoms vary - essentially they are miniature strokes. Thus the same symptoms of strokes can be applied to TIAs with the exception that they are transient hence the effects may last only seconds to minutes with a complete return to normal function. Some typical TIA symptoms include migraine-like headache that lasts less than 10 minutes, sudden paralysis or weakness that disappears within just a few minutes. Sudden blindness, deafness, aphasia (inability to speak) or incoherent speech that returns to normal before the patient can even seek assistance.

Rarely does unconsciousness result from a TIA, but if it does it may indicate that a more serious condition is developing. Repeated strokes or TIAs may result in scar tissue formation that leads to seizures or even epilepsy. We will begin our coverage of that topic in the next blog.

Teddy's Rat Lab

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Ethanol, the Science behind the story...

All Boozed Up...

Monday Funnies

Medical Marijuana

early posts

Curious things we learned from epilepsy surgery...

Monday Funnies

Introducing the LabRats

Seizures and Epilepsy

All seized up..

Monday Funnies

TIA - the "temporary stroke"

Monday FUnnies (on Monday! this time)