But Not TWO Miles...

For example, if you were to ask a person to walk a mile to get a thick, juicy steak or ask them to walk two miles to get the same thick, juicy steak, it’s pretty obvious that most people would take the easier way to the food.

This has been codified as the Law of Less Work:

If two or more behavioral sequences, each involving a different amount of energy consumption or work, have been equally well reinforced an equal number of times, the organism will gradually learn to choose the less laborious behavior sequence leading to the attainment of the reinforcing state of affairs. — Clark Hull, Principles of Behavior (1943)

By analogy, and probably by common sense as well, it seems likely that we do the same with mental work as well.

However, it’s not that easy to make the leap.

In the case of physical work, it’s pretty simple to figure out how this would work in evolutionary psychology. You wouldn’t want to expend 1000 Calories to get 500 Calories worth of food energy. Similarly, you wouldn’t expend 1000 Calories to get 2000 Calories if there was a way to get it for 500, half the “price”. Animals that consumed more energy than they needed starved to death. That left the “efficient” animals to reproduce and pass that efficient behavior on to their offspring.

But in terms of food energy, it takes just about as much to think of one U.S. President as it does to think of all 43 U.S. Presidents. If you can get that steak by just naming one, what kind of maroon would name all of them, in order?

Well, someone like me, for example.

Psychological research rides to the rescue, in the form of a paper by Kool, McGuire, Rosen and Botvinick published in last year’s Journal of Experimental Psychology (General).

One side benefit of abstracting this paper for my audience is that I can call it “The Kool paper” which seems right somehow. Unfortunately, Kool and McGuire contributed equally to the project so it really should be “Kool and McGuire et al.” but that doesn’t have the same ring to it.

In this Kool paper, they decided to test the mental work version of the Law of Less Work as laid out by Allport:

We like to solve problems easily. We can do so best if we can fit them rapidly into a satisfactory category and use this category as a means of prejudging the solution. — Gordon Allport, The Nature of Prejudice (1954)

Allport, not surprisingly, was concerned with the prejudgments inherent in prejudice (after all, that’s where the word comes from). One view of prejudice is that it simplifies life, by reducing the cognitive demand necessary to make judgments. As the Onion headline puts it, “Stereotypes Are a Real Time-Saver”. For example, if I have an event of extremely low probability (being robbed at gunpoint) and I can find an easy way to simplify my decision-making (all the robbers I know of are black, so I will avoid black people) then I can convince myself with a neat bit of post hoc ergo propter hoc that my prejudices are well-founded and rational. (I didn’t go into that black neighborhood, and I didn’t get robbed, so I must’ve been right.)

In my neuroscientist view, I’ve promoted the same idea. Regular readers of this blog know this dogma already, but for those of you who are new around here:

The brainstem is a small, tightly connected, and essentially hard-wired piece of neural real estate that controls our state of alertness, heart rate, breathing rate, and so forth. It’s tightly interconnected with the hypothalamus, not technically part of the brainstem but still part of the unconscious nervous system. As physiological psychologists are fond of joking (this joke goes back to at least the second edition of Neil Carlson’s magnificent textbook on the subject), the hypothalamus controls the four Fs: feeding, fighting, fleeing, and mating. Ba-dump.

The limbic system, the emotional part of the brain, also appears to operate at a subconscious level. For example, we’ve talked about the role of the anterior cingulate cortex in expressing political views. The anterior cingulate is also important in an “emotional Stroop test“, where a person needs to control an emotional response to words they’re reading. The amygdala, also part of the limbic system, is important for triggering anger and fear in response to appropriate (or, sometimes, inappropriate) stimuli.

All this deciding and doing happens without the participation of the rest of the brain, and is an essential part of your day-to-day activities.

What distinguishes humans is the size, complexity, and variety of their cerebral cortex. Mother, or your ethical framework, or your culture (really, all of the above) reside in the prefrontal cortex, with the rest of the cortex making high-level decisions about Other Important Stuff. We like to think that being human means that the cortex rules, but that’s simply not the case. In many respects, the brainstem and thalamus run the show and the cortex just gets to weigh in on relatively mundane things like what restaurant to go to.

The Kool and McGuire paper didn’t really test my dogma, as stated above, because it looked at two ways of using the cortex, a simple way and a more complex way. Still, I think it gives us some important clues as to how the brain works, and supports the concept of stereotyping as a time-saving device.

Kool and McGuire asked, does the “Law of Least Work” apply to mental work as well as physical?

To test this, they came up with cognitive tasks that, as Tina Turner famously observed, could be done “nice and easy” or “nice and rough”. They call these “demand selection tasks” because participants are choosing the level of cognitive demand they want. The participants were given images on a computer screen that looked like a deck of cards, with a numeral on each. The task was to select either “odd” or “even” when presented with the “card”. In the low-demand “deck”, the even numerals were mostly one color and the odd numerals mostly another. In the high-demand deck, the odd/even category did not match the color category.

It’s interesting to me, because what I do instinctively on slides I present to my students is try to reduce the cognitive demand they put into reading the slide, so that they can focus energy on the cognitive demand of the material itself. For example, in the labeled diagram shown here, I’ve matched the color of the connective tissue sheath in the artwork to the name of the layer by using Photoshop’s eyedropper tool to sample the color on the image and match it to the text. This reduces the students’ cognitive effort to figure out which label goes with which layer of muscle, in the same way the Kool and McGuire task reduces the cognitive demand of choosing odds or evens.

Of course, the first time participants worked at the task, it was 50/50 which virtual deck they would choose. However, over repeated trials, they eventually chose the “easier” deck about 3/4 of the time, as shown in figure 2 from the paper.

I’m interested in how this might reflect, not only on our prejudices, but in our political decisions. Do people choose the candidates and party based on what’s easiest (“my Daddy voted Demmycrat, so I vote Demmycrat too”)? Perhaps our political decisions, as so many decisions in our lives, are not made based on cortical information processing but rather on whatever choice is easiest for us.

Delusions of Gender

It seems the only uninterrupted (read: Internet-free) time I have to read is on airplanes. The time between boarding and achieving cruising altitude, and the mirror-image process of landing, is a time that all electronic devices are stowed, and therefore a perfect time for an old-fashioned, paper and pasteboard book.

I was sitting on the plane to Seattle, engaging in my usual practice of “eavesdropping” on what the person to my right was reading.

It was the book Bringing Up Boys by James Dobson. The passage at the top of the page he was reading (page 15, to be precise) said:

“Think for a moment about the above quotes from Steinem, Greer, and the other early feminists. Most of them were never married, didn’t like children, and deeply resented men, yet they advised millions of women on how to raise their children and, especially, how to produce healthy boys. There is no evidence that Steinem or Greer ever had any significant experience with children of either sex. Isn’t it interesting that the media (to my knowledge) never homed in on that incongruity? And isn’t it sad that these women were allowed to twist and warp the attitudes of a generation of kids?”

What I was reading was like a sort of Ode on a Grecian Urn of Nonsense, a perfection in stupidity. How did Dobson know that early feminists “deeply resented men” and “didn’t like children”? That damn mainstream media dropped the ball again, by refusing to expose the perfidy of people fighting for basic human rights. I’m not even sure what the evidence is for either Steinem or Greer “advis[ing] millions of women on how to raise children”. Sure, I know they wrote on the subject, but as an adolescent at the time, I don’t recall a lot of my peers’ parents following Greer’s advice to raise us like Tahitians. I don’t recall a single lavalava being worn to classes in my high school.

Meanwhile, over in the book I was pretending to read at the time, Delusions of Gender, I could have been reading how a miniscule amount of neuroscience had been turned into a defense and bolstering of Dobson’s moss-backed attitude towards sex roles.

Fine takes issue with the current crop of “Men Are From Mars, Women Are From Venus” books, that claim an innate, immutable set of talents which are possessed by Y chromosome owners as a result of the bathing of brain cells in testosterone in utero. Of course, such books also claim that bathing brain cells in estrogen produces the exact opposite effects: active vs passive, destroying vs nurturing, even folding maps properly vs being charmingly unable to use a map. One can almost hear Rex Harrison as Prof. Henry Higgins singing “Why Can’t a Woman Be More Like a Man?” whilst reading these horrid books.

Fine needs no reductio ad absurdum to demolish these works. They’ve become fully absurd all on their own.

Areas where I agree with her argument, then, are found right up front:

• Genetics is not destiny;
• It’s absurd to reduce the complexities of human behavior to a few bumper-sticker phrases.

She points out, quite accurately, that even where scientists find statistically significant differences in abilities between males and females, these findings obscure two huge concerns.

An underlying concern that is lost when books are written and marketed is that even for tasks in which males and females are clearly different to scientists, the areas of overlap are much larger than the areas of difference.

Plot of male and female scores on the mental rotation test. The scores are plotted on the horizontal axis; the number of people achieving each score is on the vertical axis.

To illustrate this point, I’ve taken one test that Fine covers in her book, the rather famous Mental Rotations Test. Study after study has shown gender differences in the test. One such recent study is by Titze et al. (J Individ Diff 29:130-133, 2008). I plotted this data from this study.

Can you tell, just by looking at these curves, which one represents the male and which the female? This would be considered a huge and robust gender difference in performance, yet most laypersons looking at these graphs would not find them much different. Put another way, if all you had in hand was a person’s score on this test (a number on the horizontal axis), could you accurately predict whether they were male or female?

Second, the findings used may not be universal and genetic, but rather a product of cultural norms.

So far, so good, in terms of my enjoyment of the book and our areas of agreement. It would be sad to think that I only enjoy books that I agree completely with, but I’m willing to accept that as a possibility.

Still, if I find myself as a member of the choir being preached to, I’m likely to tune out the rest of the sermon. I have a lot of science books on my shelf that I read to page 30 or so and then gave up on, because they became boring, obvious and repetitive. I like my perceptions being expanded in new directions.

I believe Fine takes a wrong turn in trying to hammer her argument home. Just because a simplistic, genetics-only explanation is not correct, it does not follow that a simplistic, environment-only explanation IS correct. I studied psychology as an undergraduate in the 1970s, when the environment-only explanations were de rigeur. If a baby smiled, it was because she received positive feedback from her mother and that made her smile more. If a baby had a cranky temperament, it was because the parents made it so. They should stop doing that.

This was, of course, nonsense, and easily destroyed in the crucible of experience and common sense.

Neuroscientists like me avidly participated in the building of what Fine calls, in a wonderful turn of phrase, “neurosexism”. Neurosexism, Fine correctly points out, is taking old notions of gender roles (as exemplified by Dobson) and dressing them up in the new, shiny gowns of neuroscience. This makes them apparently impervious to criticism. “I’m not a sexist! I’m only reporting on what neuroscience tells us!”

So Fine’s mistake, as I see it, is to come down too firmly on the “nurture” side of the age-old “nature vs nurture” argument. In doing so, she ignores a body of literature which argues for the “nature” side. Perhaps she feels that the examples are too familiar. One ignores the power of genetics at one’s peril, however.

This is the missed opportunity: to me, behaviors result from a complex mixture of genetic and environmental forces. The answer to the question “nature or nurture?” I think should be “neither, both, yes”. Just as there are very few diseases that can be attributed solely to genetic makeup, there are very few behaviors that are purely genetically determined.

I know why we search for simple answers, but I also know why people crave Cheetos. That doesn’t mean it’s a good idea to overindulge in either. There is no simple answer to this question. Trying to destroy one simple answer (“it’s genetics that make me act like a typical male”) with another (“it’s culture that makes me act like a typical male”) doesn’t advance the field very much, I think.

In the process of arguing with Fine as I read her words, I learned something new. I credit Fine with opening my mind to a completely new way of thinking. As I persisted through the middle passage of the book and made it to the last third, I found an intellectual gem. I had been trained and schooled to believe “environment” consisted of the direct, one-on-one interactions between two people, or perhaps even the physical world.

Fine makes a strong case for the power of culture, a force that I had not fully considered before. Using both anecdote and literature to maximum effect, she shows how babies respond to cultural cues as they try to assimilate into the new world they find themselves in.

But here’s the problem: if a baby is born with a strong desire to assimilate into the culture he finds himself immersed in, isn’t that evidence of a genetic propensity to do so? The “hard-wiring” that causes an anaphylactic reaction in Fine is here, but for some reason she can’t bring herself to acknowledge it. Instead of a hard wiring due to hormonal influences, this is the idea that a baby is hard-wired to fit in. I suppose that’s something we can all agree on, because I find it uncontroversial and yet still a fascinating insight into what drives gender differences.

(To be fair to Fine, after I read her book I found this video, in which she answers a question about epigenetics with pretty much an ideal answer. I wonder if her near-polemical focus on clasting the icons of neurosexism was the result of editing and marketing, and not necessarily a true reflection of her feelings about the interaction between genetics and environment.)

I’m going to continue to argue for a complex stew of genetics and environment as the dish from which we draw ladles of behavior. However, after reading Fine’s well-written and approachable book, I’ll perceive a new category of ingredients that I had not appreciated before.

I would place culture in a separate category with a powerful pull of its own. Just as genetics has epigenetics as an offshoot of the category of inborn traits, I now believe “environment” or “nurture” should be subdivided into the physical world, interpersonal interactions, and the power of culture. I thank Cordelia Fine for opening my eyes to that insight.

I intended to spend my summer producing and editing videos, but I wanted to do that on my own content. Instead, because of a miscommunication that wiped out wide swaths of our existing lecture content, I have been spending the last few weeks producing and editing videos to be used in our anatomy & physiology course.

Most of these are specific to the course, but this one is a general introduction to molecular biology.

Recently, my Twitter account was filled with a back-and-forth between an earnest young female scientist who had met, and was taken by the intellectual prowess of, James Watson. A number of us old hands, from many different fields, jumped on her a little more than we should have, telling her about the wrongs that he had perpetrated on science in general and molecular biology in particular.

For example, Ivan Oransky of the excellent “Retraction Watch” and “Embargo Watch” blogs had written an Op-Ed on the subject of James Watson’s crude nonsense for the Boston Globe.

No more august an authority on unpleasant behavior than E.O. Wilson called Watson

the most unpleasant human being I have ever met

which is a sentiment you will hear echoed often, from my brief personal exposure all the way to those who knew him best.

It was in the spirit of trying to pass along to a new generation the bitter lessons of the previous generation that informed me as I sat down to discuss what I call “The Original Sin of Molecular Biology”.

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.

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”.

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.

Gluttony

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.

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.

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.

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.

Source: mdsystems.com

As scientists explored this mutation, they found that ob/ob mice lacked a leptin receptor. The iceberg that changes the leptin signal into action was gone, and even though the stomach wall produced plenty of leptin hormone — “Stop eating! Stop eating! You’re full!” — that signal never reached its target. The radio station was strong, but none of the resident mouse cells had a radio tuned to pick up the signal. As a result, the mouse kept eating and eating. In short, a gene mutation, inherited from their parents, saddled them with the sin of gluttony.

These three are the signals sent by the stomach to tell the medulla how that Oreo is progressing: ghrelin to stimulate eating, and leptin to stop eating, along with stomach stretch signaled directly from the stomach muscles to let the brain know how full the stomach is.

Further down the gut tube, the small intestine has its own suite of hormone signals. In the duodenum, the fat in the Oreo filling spikes a hormone called cholecystikinin, “CCK” to his friends. “Chole-” means “bile”, the same word root as “cholera”, thought by the ancient Greeks to be caused by an excess of bile.

Source: BBC

Remember that bile is used to emulsify fats — break them into tiny bubbles that can be absorbed by the gut and passed into the bloodstream. The wheat protein in the cookie wafer of the Oreo also stimulates CCK. The middle syllables, “-cysti-,” refer to a fluid-filled sac, a bladder, in this case the gall bladder. The suffix “-kinin” signifies movement, in this case, the movement of bile from the gall bladder into the duodenum. CCK also signals the medulla of the brain, letting the brain know that the Oreo is larded with lipid.

The sugar part of the Oreo, converted mostly to the simple six-carbon sugar glucose, is absorbed in the remaining twenty feet of small intestine. There, it triggers release of a hormone which also acts as a neurotransmitter, the semi-famous serotonin.

Serotonin is an amino acid, one of the pearls which strung together make up peptides (if there are several or dozens of pearls in the string) and proteins (if there are hundreds of amino acid pearls). Many people know serotonin from its role in regulating mood. For example, the antidepressant Prozac works as a “selective serotonin reuptake inhibitor” (SSRI), blocking the molecular sponges that sop up serotonin where nerve cells come together. The excess serotonin left behind in the synapse elevates and smooths mood.

Source: Good Housekeeping

Many people feel that serotonin from food has an effect on mood as well. Some foods, like your Thanksgiving turkey, have serotonin as a minor component. Other foods, like the Oreo, have a high sugar content that triggers the release of serotonin from the intestines.

Another intestinal hormone signal is peptide YY, which like leptin from the stomach, acts to reduce gluttony. Both the tenth cranial nerve (vagus) leading back to the medulla and a crescent-shaped sliver of tissue in the hypothalamus, the arcuate nucleus, seem to have PYY receptors.

Glucagon-like peptide-1 (GLP-1) is a final intestinal hormone that acts on taste centers in the medulla and also a part of the brainstem called the area postrema. Stimulating the area postrema leads to vomiting, but the GLP hormone seems to have a less dramatic effect.

GLP is a cousin to an enzyme called glucagon which is released from cells in the pancreas. The most famous of the pancreatic hormones, insulin, causes glucose to be mobilized from the bloodstream into hungry cells in all organs of the body. On the other hand, glucagon moves glucose into the starch-like molecular complex called glycogen so that, in times of need, the body can tap its energy reserve — about 2000 calories — held in glycogen storage in the liver and muscles. For example, marathon runners famously “hit the wall” after about 20 miles, a distance that takes 2000 calories of energy to cover. At that point, the glycogen “tank” is empty and other reserves, more difficult to convert to energy, must be tapped.

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.

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.

Source: http://dogsforlife.wordpress.com/2011/02/25/a-dogs-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.

(Video of how Monique makes this work for her and her partner Basil.)

Force-based methods, or methods based on half-baked “theories” like dominance theory, look great on TV but don’t work and may well do significant harm to dogs, just as they would to humans. Ethical, behavioral-based therapies may not work, but they won’t hurt your dog, or your relationship with your dog.

I’m interested in how dog brains work, in the same way a human therapist might be interested in how human brains work.

One open question — and likely a completely unanswerable one — is how dogs’ brains got that way. (For fun after-dinner conversation, or for blogs, nothing is better than an unanswerable question.)

Genetic evidence suggests that dogs were domesticated independently at several different locations at about the same time. Dog domestication probably happened about 32,000 years ago. Paleoanthropologist Pat Shipman believes that dogs were first raised as hunting tools, then became companions and even food in very lean times.

A really good tool. Photo: Jeff Jaquish, zingpix.com

If this is true, it means that dogs and cats were the first animals domesticated for humans as a tool to act at a distance. Some animals were for food. Others were tools used to pull a sled or a plow.

Raptors and carrier pigeons act at a distance, but were used much later and without much domestication. Falconry appeared about 3000 years before present (YBP) and carrier pigeons were developed about the same time.

Dogs and cats could work semi-independently, increasing the range over which a human could act to as much as several hundred meters. Like the atlatl and bow and arrow, both developed in the same range of human prehistory (about 40,000 YBP), dogs and cats allowed prehistoric humans to exert action at a distance. This would be a tremendous advantage over having to (say) club a woolly mammoth to death with a stone ax.

Dogs would have been raised for their ability to work with humans hunting in packs, for example cutting a weak animal from a herd of buffalo so that humans could bring it down and kill it. The dogs would get the entrails and bones as food, and the humans would butcher the animal for the part the dogs were less interested in, such as the muscles and hide.

The story for cats would be different. In the eternal struggle between humans and rodents — rodents always stealing and spoiling human food, causing disease and starvation — humans have only recently gained the upper hand. The enslavement of rats and mice as research animals is their race’s penance for the original sin of starving my ancestors and killing them with biowarfare agents such as the bubonic plague.

Cats would be the roving secret agents in the war on rodents, allowed to operate independently with minimal supervision.

Dogs, on the other hand, would be allowed to live in close proximity with humans, even sleeping with them. Dogs who could “read” their masters and could work as a brainy tool at a distance would be prized. We see this as the dog sports of obedience, herding and agility to this day. Each of these sports consists of utilizing the invisible leash between humans and dogs to spectacular and pleasing effect.

(For wonderful still images of dogs herding, see Jeff Jaquish’s Flickr page. For books about dog agility, including mine, see Cleanrun.)

Early genetic evidence suggested that dogs were developed in East Asia. More recent studies suggest that another location, perhaps the Middle East, is the most likely origin. Others have argued for domestication at about the same time in multiple locations. Genetic studies are complicated by the ability of wolves to interbreed with domestic dogs, although there are no native wolves anywhere near some of the supposed domestication sites.

What were the ur-dogs? vonHoldt et al. argue based on the genetic evidence that they resembled the modern breeds of: basenji, Afghan hound, Samoyed, saluki, Canaan dog, New Guinea singing dog, dingo, chow chow, Chinese Shar Pei, Akita, Alaskan malamute, Siberian husky and American Eskimo dog. This makes sense both based on the genetics of these dogs, but also the many uses of domesticated dogs. For example, the dingo and its cross with a now-disappeared British herding dog, the Smithfield, produced the Australian Cattle Dogs pictured above. As you look down this list, you see “alarm” dogs, protection dogs, livestock management dogs, and sled-pulling dogs. This probably points to the reasons for domestication.

This also supports Shipman’s theory that dogs were working tools before they were food, since there seems to be more diversity based on working style than on body type.

What did domestication do to the dog’s brain? A number of years ago, a friend and colleague who studies the prefrontal cortex — the part of the brain where our “mothers” live, responsible for “conscience” and social behavior — made a provocative statement at her seminar. Grazyna Rajkowska said based on fossil cast evidence, “dogs and cats started with the same amount of prefrontal cortex,” but through domestication, dogs developed a prefrontal cortex while cats did not.

She was referring to studies by Leonard Radinsky that correlated hunting behavior in canids with the development of various brain regions. Since brains don’t survive the fossilization process, paleontologists are forced to infer the structure of the brain from the skull that surrounds it. This works pretty well because the inside surface of the skull is soft in infants and is partially molded by the development of the brain. Radinsky sadly died at the age of 48, so he’s not here to defend himself, but I will try to do justice to his work.

Radinsky focused on the prorean gyrus (Greek πρωρα + Latin gyrus) a bump (gyrus) that resembled the prow of a ship (πρωρα, prora) to some early neuroanatomist. The brains of pack-hunting animals have a larger prorean gyrus than the brains of ancestral canids (dog-like animals) and felids (cat-like animals). Here’s the prorean gyrus in a dog brain:

The prorean gyrus in the dog's brain. Base image: http://vanat.cvm.umn.edu/grossbrain/Pages/BrDivPgs/BrDgLat3.html

Hunting carnivores — dogs and wolves and their ancestors — have a much larger prorean gyrus. Thus, we guess that much of the circuitry needed for hunting behavior is located in the prorean gyrus.

This would include watching other members of the pack (or, later, your human master); watching the prey and the prey’s cohorts; and knowing, without checking, exactly how to modify your attack based on what you see, smell and hear. It’s really a great example of how complicated behaviors can be packed into a relatively small amount of brain real estate.

Cody, a dolichocephalic, lure coursing dog.

Radinsky’s findings are consistent with more recent scientific evidence. Roberts, McGreevy and Valenzuela published a study last year in PLoS One that showed how domestication has changed the anatomy of the dog brain. It’s well-known that dolichocephalic dogs (such a greyhound) are much better lure coursers and hunters than brachycephalic dogs (such as a spaniel).

Brachycephalic dogs (let’s call them “round-headed”) have a brain that is rotated and the olfactory lobe is displaced upward. The correlation between round-headedness (measured by the cephalic index) and upward displacement of the olfactory lobe is quite strong, with a correlation (r) of 0.971. This means that about 94% of the variation in olfactory lobe position is explained by the cephalic index, and vice-versa.

As Roberts et al. put it (p. e11946):

Because differences in cranial morphology across dog breeds were closely associated with major neuroanatomical changes, whether these also lead to differences in behavior is a major open question.

It’s provocative, isn’t it? The exact area where domesticated dog brains seem to have changed the most, the prorean gyrus, is exactly where human social behavior (“manners”) tend to reside in the human brain, where brains got bigger in dog-like ancestors that hunt for a living, and where the biggest changes occurred in the domestication of the dog.

It’s time we changed the old joke, “Dogs have owners, cats have staff” to “Dogs have a prorean gyrus, cats don’t.” Okay, so maybe I need to work on that.

For those interested in this topic, I highly recommend the book Dogs: Their Fossil Relatives and Evolutionary History by Wang X and Tedford RH. I downloaded it to my iPad while working on this article. I love this modern world.

Thanks to Tracy Smith and Rosemary Hoffman for comments leading to critical edits in the human prehistory and tools section.