May 2011
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Month May 2011

Teaching Thursday: Clinical Problem Solving in Hematology

My students consistently have problems with clinical problem solving in the Introductory Pathophysiology course I teach. The first time they hit this type of problem is in the first organ system we study, hematology.

This video explains how to break down clinical problems into a manageable set of steps. Of course the hematology is much simplified, but this is the students’ first exposure to the pathophysiology of this organ system.



Under the Spreading Neurotree

We were on the train to Salt Lake City, the student and I. She was considering a neuroscience minor, and I wanted to introduce her to some high-powered neuroscience at the next opportunity.

Our college/working class town doesn’t have much in the way of neuroscience lectures, but luckily, the University of Utah’s Brain Institute is only an hour’s train and light rail ride away, and so we were on our way down to hear an old friend, Dr. Ed Rubel, speak on his research.

Rubel is one of the smartest guys I know, and he’s a wonderful and engaging speaker. I’ve known him since 1985, when I came to work with my postdoctoral advisor, Dr. Vivien Casagrande.

We arrived early, and waited in the lecture hall. As we became bored with watching the proper connections being made to make Rubel’s slides display on screen, I was explaining to Megan, the prospective neuroscientist, my connection to Rubel.

“Well, Ed Lachica was a graduate student in Casagrande’s lab at the same time I was a postdoc,” I explained. “Ed Lachica went to Ed Rubel’s lab for his postdoc, after he finished his degree with Vivien. So I suppose Ed Rubel is like my scientific father-in-law, if Ed Lachica and I are sons of different fathers.”

She laughed. This seemed complicated, and a little bit strange to her, I could tell.

“Neuroscientists are all connected, one way or another. In fact, there’s a website called NeuroTree where they compile the connections and display them as a sort of ‘Neuroscience Family Tree’.”

This seemed fantastical to her, so I whipped out my iPad and proceeded to show her.

As I did, as if on cue, another neuroscientist/educator, Suzanne Stensaas, was chatting with Rubel.

“We’re brother and sister, I think,” she was saying.

Megan’s eyes opened wide in amazement. My credibility increased then and there.

Yes, there is a NeuroTree. The entries there are all made by contributors, to avoid a certain kind of vandalism or perhaps even the claim of a false connection. I’m on there, as are most of my colleagues, and if you want to see how we’re connected, then you can go there too.

It allows for a neuroscience version of the “Kevin Bacon game” or “Six Degrees of Kevin Bacon” (a takeoff on the meme “Six Degrees of Separation“) where one tries to construct a path with the minimum number of steps between Kevin Bacon and anyone

Me (Bowling for Boobies) →

1. Jane Wiedlin (“Bill & Ted’s Excellent Adventure“) →

2. Clifford David (“Pyrates“) →

3. Kevin Bacon! Just three degrees between me and Kevin Bacon!

or Kevin Bacon and anyone in Hollywood.

How many steps between me and Rosanne Cash? Fourteen!

James B. Hutchins (Weber State University)
|    (grad student for)
Frank S Werblin (University of California, Berkeley)
|    (grad student for)
John E Dowling (Harvard University)
|    (grad student for)
George Wald (Harvard University)
|    (trained grad student)
Merle S Bruno (Hampshire College)
|    (grad student for)
Donald R Griffin (Harvard University)
|    (grad student for)
Karl Spencer Lashley (Harvard University)
|    (grad student for)
Robert Mearns Yerkes (Yale University)
|    (trained grad student)
Kenneth W. Spence (Iowa University)
|    (grad student for)
Clark L Hull (University of Wisconsin)
|    (trained grad student)
Neal E. Miller (Rockefeller University)
|    (trained grad student)
Gordon H Bower (Stanford University)
|    (trained grad student)
Douglas L Hintzman (University of Oregon)
|    (trained grad student)
Daniel J Levitin (McGill University)
|    (close friends with, appears in video with)
Rosanne Cash

(I had no idea I was so close to Karl Lashley. There exists no engram in my brain for that information.)

Feel free to post below if you think we’re “related”.


Seven Deadly Sins Sunday: Gluttony Part 5


In Part 1 of “Gluttony”, we set up the concept of Seven Deadly Synapses the book.



In Part 2, we looked at how an Oreo cookie is broken down and ends up either becoming a part of us, or being released in the toilet.

In Part 3, we looked at our motivations for eating, and how they might be altered by chemicals made by our bodies, or even chemicals coming from hitch-hiker microbes.

In Part 4, we saw how our genes may be driving the process of gluttony.

This is the last installment in “Gluttony”. Before we leave this sin, we’ll take a visit to Dante’s vision of Hell, and his view of the Gluttons.


Part 5

Gluttony, then, is when the body takes in more energy than it needs. “Need” is defined by a complex mix of hormones, hypothalamic settings and body composition. If the glycogen tank is empty, the first 2000 extra calories are stored as glycogen, ready on a moment’s notice and easily burned. When the glycogen tank is full, at about 2000 reserve calories, then the excess is stored as fat, which is harder to get rid of and not so easily burned. The balance can be tipped toward fat storage by the hormonal makeup of the body, and as we’ll see, the hormonal balance is tipped by fat storage. It’s a complicated example of what scientists (influenced by engineers) call a “positive feedback loop”.

Fat has a lot of chemical bonds. All those bonds in fat contain a lot of chemical energy. When the fat is broken down, that energy is released. Fats in our food give us about 4000 calories per pound; proteins and carbohydrates (sugars), less than half that.

Nutritionists estimate that it takes 3500 excess calories to store one pound of fat. (If a pound of lard contains 4000 calories, the other 500 calories were used to digest, synthesize and package the fat as it moved from our mouths to our bodies.)

Fat (“adipose tissue”, if you want to be polite) is a selfish organ. It uses hormonal signals to command the formation of more fat. More of the body’s energy is then stored as fat, and the cycle spirals ever downward, towards overeating and obesity. The body takes in excess food calories; the extra calories are stored as fat; the fat directs the body to seek out more calories; the body takes in excess food calories. Gluttony ensues.

As Dante and his party descend to the third circle of Hell, not far from the entrance and so inhabited by a sort of minor sinner who is still subjected to unspeakable torture, they encounter the Gluttons.


The health effects of gluttony, and the social stigma that goes along with it, makes its victims want to approach the perfection that Dante’s sinners craved. Still, gluttony is a tough nut to crack. The mechanisms that control “normal” feeding behavior are complex. Our understanding of the ways in which fat works as an endocrine (hormone-releasing and hormone-receiving) organ are incomplete. Over and over again, scientists have identified a “magic bullet” such as leptin, only to find that the system is designed with multiple control loops, all knotted together and all designed to be resistant to any intervention. No single factor seems to be enough to banish gluttony.

The stakes are high. Fat’s effect on health are well-known, and it would only make me a scold to recite them. Obesity almost always leads to a follow-along disease, only defined in the last few dozen years, called “Syndrome X” or, more recently, “metabolic syndrome”.

Metabolic syndrome is comprised of: a waistline that is too broad, too much cholesterol in the blood, increased blood pressure, too much sugar in the blood, a tendency of the body to overreact to damage, and a propensity for the blood to clot.

Let’s take these one at a time. A waistline too broad (more than 40 inches for men, 35 inches for women) explain what you’ve heard about the “apple” body type (lots of fat around the waist) versus the “pear” type. Somehow, fat deposited around the waist seems to be different, probably because it tends to release more hormones.

Cholesterol is needed to make the wrappings which keep your cells intact, but too much of it can deposit in the arteries. Cholesterol can’t travel by itself in the blood; it needs to be shepherded to the cells by a carrier protein. Most people have seen the cryptic terms “HDL” and “LDL” on a lab report after their blood is analyzed. The different combinations of lipid and protein form the different subcategories that labs measure. You know from the last time you made gravy or chicken soup that fat floats; floating means low density; so “low-density lipoprotein” (LDL) contains more fat than protein, and that’s the more dangerous kind of cholesterol.

Increased blood pressure occurs because the body is under constant stress; there are more blood vessels, they are narrower than they should be, and they get clogged with fat and clots.

Increased blood sugar is the hallmark of type II diabetes mellitus. Remember the role of the hormone insulin: to move glucose from the blood into the tissues of the body, which need it for energy. As far as we know, something in the hormonal mix caused by the presence of fat causes less insulin to be released, and the insulin that is released doesn’t work the way we expect. It’s a paradox: cells are starving, and cry out for more glucose, but because they have become “insulin resistant”, insulin is unable to effectively move glucose into the cells. Less glucose is absorbed by the cells and it accumulates in the blood.

Inflammation is the general term for the body’s response to injury. If something damages you, or if an invader tries to occupy your body, it’s the inflammatory mechanism that kicks in right away. Inflammation carries risks, however; inflammation in the absence of injury or invasion is doubly dangerous. Metabolic syndrome includes an increased tendency to inflammation. Currently, we don’t have very good ways of measuring this, but a substance called “C reactive protein” is the best yardstick we have.

Increased blood pressure, more lipid deposits on the inner walls of arteries, and increased inflammation, all lead to blood clotting. Let’s say there’s a hole in you. As blood squirts out, there are ripping forces that stimulate specialized cell fragments and proteins in the blood to form clots and plug the hole. In the case of metabolic syndrome, blood pressure, fat deposits clinging to the walls of blood vessels, and roughening of the walls of blood vessels all work to increase the ripping forces on blood. Clots form where they shouldn’t, inside of blood vessels, and then can travel to the lungs, or heart, or brain, causing tremendous damage wherever they lodge — deep venous thromboses, heart attacks, strokes.

I’ve fought gluttony, and I was aware that something needed to be done long before I was able to do anything. It’s not easy. After my successful weight loss, I became a support group leader. Now, I see others fighting the perceived sin of gluttony, and I can see how hard it is to fight alone. It is clear to me what a powerful adversary gluttony is.

Why do some methods work better than others? None works particularly well. The range of choices lies between near-impossible and total failure. In one recent study, people who followed a diet lost an average of two pounds in a year. People who followed a diet and attended a support group lost six pounds in a year. Most of us would find that a minimal benefit. The secret is in the math: if one person loses sixty pounds, but nine others lose nothing, then the average weight loss is six pounds for those ten people. Even the “best” method doesn’t work well. We suffer under the pressure of our fallible human genes, pushing us to gluttony, and we’re driven by hormones and brain circuits that are mostly out of our control. The two weapons we have are willpower and the moral force of groups.

Studies have shown that people gain, or lose, weight in social groups. Just like the body itself has homeostatic balancing mechanisms to regulate a preferred level of substances like glucose in the blood, it seems that people interact with each other to influence their own set points. We get fat in groups, and we lose in groups. Clearly, social support mechanisms (or lack of them) have a tremendous influence on people’s behavior, which we’ll revisit as we look at “Temperance.” Tiny, atomic-level feedback loops in the body’s chemical reactions are controlled by larger feedback loops in cells and hormones, which are controlled by still-larger feedback loops operating at the level of clubs, churches, friendships and families. No wonder we find it so hard to understand the sin of gluttony, much less control it.

Teaching Thursday: Pedigrees

This Thursday’s teaching video is a primer on pedigree analysis.

Even though their use has fallen out of favor, as we begin to better understand the complexity of genetic diseases, a pedigree is still a pretty good place to start as students begin to learn the basics of Mendelian inheritance: autosomal vs sex-linked modes of inheritance, and dominant vs recessive mutations.

Sure, we know the world is a lot more complex than this. But it’s still good to start with relatively simple pedigrees, so we can build from there. Today’s video is a brief introduction to Mendelian genetics and pedigrees.




Seven Deadly Sins Sunday: Gluttony Part 4


In Part 1 of “Gluttony”, we set up the concept of Seven Deadly Synapses the book.



In Part 2, we looked at how an Oreo cookie is broken down and ends up either becoming a part of us, or being released in the toilet.

In Part 3, we looked at our motivations for eating, and how they might be altered by chemicals made by our bodies, or even chemicals coming from hitch-hiker microbes.

In this Sunday’s installment, we’ll talk about how our genes may be driving the process of gluttony.


Part 4


Before the revolution in gene sequencing of the last three decades, which culminated in the Human Genome Project, the main way for genetic researchers to study disease was to catalog and sift through the spontaneous mutations that arose in laboratory mice. For years now, to make genetic research possible, different strains of laboratory mice have been inbred for hundreds of generations. Now, each individual mouse of a strain is essentially an identical genetic copy of its father and mother, a duplicate of its cousins and siblings, and the original from which its unborn descendants are copied.

For example, a kind of shiny black mouse called “C57Bl” is an inbred strain; all mice of this type are genetically identical, except for mistakes and random changes made in the copying process. In one of these mutations, mice begin to get fatter and fatter starting at about four weeks of age, about the time the mice reach sexual maturity. As adults, they’re grossly obese, barely able to move around their cages. Genes are named with a short designator, and since there are two copies of each gene, one from the mother and one from the father, the names of the two gene types are separated with a slash. Because of this obesity, mice that carry two copies of the mutation that makes them fat are called ob/ob mice.

Teaching Thursday: Liability Threshold

Our Teaching Thursday video-of-the-week is about liability threshold.

This is part of a model of human disease that says that it usually takes multiple “hits” before a cell, a tissue, or even a person suffers disease.

These “hits” can be genetic (say, a mutation); environmental (some sort of chemical insult); or may result from a complex interaction of genetics and environment.

People are born with different genetic, innate differences in disease susceptibility. As they age, they accumulate more and more “hits” which brings them closer and closer to something called the “disease threshold”. The idea is that once you cross the threshold, disease results.

In this video, the disease threshold is a vertical bar toward the right side of the population distributions. The further to the right you are on the curve when you begin life, the higher the chance you’ll have the disease.

The video (I hope) will explain the rest.


The Truth About Cats’ and Dogs’ (Brains)

As a neuroscientist and dog trainer, I’ve always been fascinated by the interface between the two.

For me, the most powerful forms of dog training utilize the secret bonds of empathy and guidance, much like a psychiatrist will act as docent to take a patient on a guided tour of their own brain.



For example, in the therapeutic school called Cognitive-Behavioral Therapy, the therapist acts as neuroscientist, suggesting hypotheses and carrying out experiments in conjunction with the patient. “Let’s hypothesize that you will be harmed by snakes, Mr. Jones. Are you saying that all snakes are harmful, or just some types?”

That’s how good, effective dog training works, as well. I have always been drawn to the power and elegance of the very best behavioral-based trainers, such as Dr. Sophia Yin, Monique Anstee and Dr. Suzanne Hetts.

Seven Deadly Sins Sunday: Gluttony Part 3


In Part 1 of “Gluttony”, we set up the concept of Seven Deadly Synapses the book.



In Part 2, we looked at how an Oreo cookie is broken down and ends up either becoming a part of us, or being released in the toilet.

In this Sunday’s installment, we’ll see how chemicals in our brain and even the bacteria that live in our gut drive this process.


Part 3

The brain not only keeps us from suffering social embarrassment from anal leakage, but also has a huge role in determining when, where, and what we eat. If gluttony is a sin, it resides in the brain, not in the automated parts of the gut that lie outside of our control. The brain is a complex organ. There are, scientists estimate, 100 billion nerve cells, about the same number of nerve cells as there are stars in the Milky Way galaxy. Each of these nerve cells makes connections with 10,000 others, on average. To make sense of such a complex organ, it’s convenient to think in terms of levels of organization, and for our purposes, we’ll consider four levels.

Nerve activity in the gut is in waves, which is what moves materials through the gut by peristalsis. Photo: Rolf Hicker

The intestines form a tube, and all along that tube is a gut nervous system. We saw this earlier when we were talking about peristalsis, the milking action of the bowel. This is a sort of  “housekeeping” function, which occurs to a greater or lesser extent throughout a lifetime. Nerve cells fire in waves, like the ebb and flow of the ocean, and like the ocean the waves can be big or little, or can come in frequently or less frequently, but they’re always there. The gut nervous system, called the enteric nervous system, is influenced by the content of the gut as well. More about this later.