The Doctor Weighs In

By Dov Michaeli , MD, Ph.D

This question often puzzled me. I can understand the need for a God, as an embodiment of people’s moral ideals. So the fact that our society, which views itself as based on moral principles, is fertile ground for the belief in an über-moral deity. The Brits, on the other hand, have a long history of scandalous, sometimes murderous, behaviors of their political leaders and royals. They are well-versed in their Shakespeare and, like him are cynical about assertions of moral superiority of authority figures. Is there any wonder why only a small minority of the British go to church? This could also be the reason why the most ferocious critics of religion are British. See, for instance Richard Dawkins “the God Delusion”, in which he argues that God is, well, a delusion, religion is a virus, and the U.S. has slipped back to the dark ages. If this sounds extreme, try “God is not Great: How Religion Poisons Everything” by Christopher Hitchens.

Why should a belief in a deity clash with acceptance of science? In fact, Dr. Francis Collins, a physician and scientist par excellence, is the director of the Human Genome Project. He is also deeply religious.

But consider this little nugget: In a 2005 Pew Trust poll, 42% of respondents said that they believed that humans and other animals have existed in their present form since the beginning of time, a view that denies the very existence of evolution. And in a 2008 Republican presidential debate, none of the five, or was it six, candidates raised their hands when asked whether they believed in evolution.

This is not the only domain where people reject science: Many believe in the efficacy of unproven medical interventions; the mystical nature of out-of-body experiences; the existence of supernatural entities such as ghosts and fairies; and the legitimacy of astrology, ESP, and divination.

It all begins in childhood.

In a review titled “Childhood Origins of Adult Resistance to Science”, two Yale professors of psychology, Paul Bloom and Deena Skolnik Weisberg, posit that the winter of our ignorance began in childhood. They review evidence from developmental psychology suggesting that some resistance to scientific ideas is a human universal. This resistance stems from two general facts about children, one having to do with what they know and the other having to do with how they learn.

"The main source of resistance concerns what children know before their exposure to science. Recent psychological research makes it clear that babies are not "blank slates"; even 1-year-olds possess a rich understanding of both the physical world (a "naïve physics") and the social world (a "naïve psychology"). Babies know that objects are solid, persist over time (even when out of sight), fall to the ground if unsupported, and do not move unless acted upon. They also understand that people move autonomously in response to social and physical events, act and react in accord with their goals, and respond with appropriate emotions to different situations.

However, these intuitions also sometimes clash with scientific discoveries about the nature of the world, making certain scientific facts difficult to learn. The problem with teaching science to children is thus "not what the student lacks, but what the student has, namely alternative conceptual frameworks for understanding the phenomena covered by the theories we are trying to teach". An example offered by the authors is the concept that the world is round; if it were a sphere, the people and things on the other side should fall off, right? Personally, I had difficulty understanding this concept until fourth or fifth grade.

This example concerns  people's common-sense understanding of the physical world, but their intuitive psychology also contributes to their resistance to science. One important bias is that children naturally see the world in terms of design and purpose. For instance, 4-year-olds insist that everything has a purpose, including lions ("to go in the zoo") and clouds ("for raining"), a propensity called "promiscuous teleology". Additionally, when asked about the origin of animals and people, children spontaneously tend to provide and prefer creationist explanations. Just as children's intuitions about the physical world make it difficult for them to accept that Earth is a sphere, their psychological intuitions about agency and design make it difficult for them to accept the processes of evolution.

Another consequence of people's common-sense psychology is dualism, the belief that the mind is fundamentally different from the brain. This belief comes naturally to children. Preschool children will claim that the brain is responsible for some aspects of mental life, typically those involving  mental work, such as solving math problems. But preschoolers will also claim that the brain is not involved in a host of other activities, such as loving one's brother, or brushing one's teeth. This dualism is not restricted to young children. The strong intuitive pull of dualism makes it difficult for adults as well to accept what Francis Crick (Nobel laureate for discovering, together with Jim Watson, the double helix structure of DNA) called "the astonishing hypothesis”: Dualism is mistaken—mental life emerges from physical processes. People resist the “astonishing hypothesis” in ways that can have considerable social implications. For one thing, debates about the moral status of embryos, fetuses, stem cells, and nonhuman animals are sometimes framed in terms of whether or not these entities possess  souls.

What about culture?

There are substantial differences, for example, in how quickly children from different countries come to learn that Earth is a sphere. There is also variation across countries in the extent of adult resistance to science, including the finding that Americans are more resistant to evolutionary theory than are citizens of most other countries.

When faced with information, one can occasionally evaluate its truth directly. If I claimed that rain comes from clouds, this is something that “everybody knows”, the evidence is all around us. But in some domains, including much of science, direct evaluation is difficult or impossible. Few of us are qualified to assess claims of the role of mercury in autism.  So rather than evaluating the claim itself, we instead evaluate the claim's source. If the source is deemed trustworthy, people will believe the claim, often without really understanding it. Consider, for example, that many Americans who claim to believe in natural selection are unable to accurately describe how natural selection works.This suggests that their belief is not necessarily rooted in an appreciation of the evidence and arguments. Rather, this scientifically credulous subpopulation accepts this information because they trust the people who say it is true.

This is not restricted to science, or to people who are not qualified to make judgments on their own. In California we have a referendum system, whereby we vote on specific issues proposed by individuals or groups. Countless times  I cast my vote on certain issues after checking who endorsed the initiative and who opposed it.

The developmental data suggest that resistance to science will arise in children when scientific claims clash with early emerging, intuitive expectations. This resistance will persist through adulthood if the scientific claims are contested within a society, and it will be especially strong if there is a nonscientific alternative that is rooted in common sense and championed by people who are thought of as reliable and trustworthy.

This is the current situation in the United States , with regard to the central tenets of neuroscience and evolutionary biology. These concepts clash with intuitive beliefs about the immaterial nature of the soul and the purposeful design of humans and other animals, and (in the United States ) these beliefs are particularly likely to be endorsed and transmitted by trusted religious and political authorities. Hence, these fields are among the domains where Americans' resistance to science is the strongest.

^{What’s to be done?}

The answer of course is what we knew intuitively all along: education, starting at a young age. This requires serious investment in science education. It requires a national commitment and political will.

Do we have what it takes?

By Dov Michaeli MD, Ph.D

“Go to the ant, my son

Observe her ways

And wisen”

King Solomon, Proverbs (free translation).

Undoubtedly you have seen pictures of those emaciated characters who practice calorie restriction in the name of living a long, long life. The normal daily diet of an adult male contains about 2000-2400 calories. The ‘calorie restriction’ people limit their diet to about half of that. They may live longer, but are they happier? Hard to tell; they are going to die hungry but maybe also happy, for the ordeal is finally over.

One of the organisms that provided the ‘intellectual’ basis for this cruel and unusual experiment in long living is called C. elegans.

Where in the world is C. elegans?

Caenorhabditis elegans (Caeno, recent; rhabditis, rod; elegans, nice), is a free-living, non-parasitic soil nematode that can be safely used in the laboratory and is common around the world. It is small (about 1 mm in length) and has a short life cycle. From egg to egg takes about 3 days, and its life span is around 2 to 3 weeks under suitable living condition. What is unique to this organism is that wild-type (normal, non-mutated) individuals contain a constant 959 cells. The position of cells is constant as is the cell number. Moreover, it is transparent. It is easy to track cells and follow cell lineages. This provides a great tool for research on how genes influence cell fate. These traits enable the study of the biology of a single cell in an intact, living organism.

The genome size of C. elegans is about a hundred million base pairs. This is approximately 20X bigger than that of E. coli and about 1/30 of that of human. But, as its genome is surprisingly similar to that of humans (40% homologous), C. elegans became an attractive organism in the study of human biology and diseases.

The insulin-like pathway of C. elegans

Among those remarkably human-like genes are the ones that control energy metabolism, and specifically those coding for an insulin-like pathway. Genetic analysis now conclusively demonstrated that several of those genes, when mutated, extended life through reducing the activity of this insulin signaling pathway; in other words, life was extended by reducing the metabolic rate. Conversely, there is now considerable evidence showing that senescence (aging) is associated with increased metabolic rate.

Therefore, a logical conclusion would be that an insulin-like pathway drives senescence in C. elegans by enhancing metabolic activity. Right? Not quite…Genetic manipulation has now demonstrated that it is the insulin-like pathway specifically in neurons, not muscle or other highly metabolically active tissues, that regulate life span in C. elegans. And consider this: in humans the neurons most sensitive to insulin are probably the hypothalamic neurons that regulate metabolism and body weight, destruction of which leads to profound metabolic impairment.

Biology never ceases to confound our most ‘obvious’ theories. Although many hypotheses were offered to explain this unexpected discovery, in truth scientists were stymied.

 A tantalizing clue

In a paper published this week in Nature, scientists from the University of Washington in Seattle reported on an intriguing discovery. They screened 88,000 chemicals for the ability to extend the lifespan of adult C. elegans. They found that a drug that was once used as an antidepressant in humans, increased lifespan by 30%. The drug, a tricyclic, is called mianserin and was marketed as Tolvol, before being largely phased out of the market.

Its mode of action is interesting; it blocks two serotonin receptors, SER4 which signals the presence of food, and SER3, which signals starvation, in C. elegans. But the blocking action of the drug is not equal—it blocks SER 4 (food available) ten fold more than SER3 (starvation). The authors state: “In this way, mianserin might potentially create a ‘perceived’ state of starvation that, despite adequate food intake, would activate mechanisms of lifespan extension downstream of dietary restriction”.

Or in other words: it is not the actual caloric restriction and starvation that is responsible for lifespan extension. It is rather the perception of starvation that causes the brain to activate the mechanisms that lead to life extension. Which may explain the original observation that disruption of the insulin pathway in neurons, and not in muscles or other ‘obvious’ tissues, that leads to prolongation of lifespan.

Another example of mind over body. Or is it perception trumps reality?

Whatever the philosophical musings this experiment evokes, the practical implication is awesome: we won't have to spend a lifetime in starvation in order to live an extra few years. Drugs will be available that would allow us to literally have the cake, eat it and live long enough to tell the tale to our great-great-great grandchildren.

Dov Michaeli MD, Ph.D is in the biotech industry

By Dov Michaeli MD, Ph.D

Have you ever wondered why do people reach for food, any food, when they are under stress? With most people, this stress reaction is mild and episodic. But in others, it is extreme and frequent; they can consume 6, 7, 8 thousand calories in a single day. This syndrome of binge eating has attracted much attention among psychologists for a long time; and now neurobiologists have taken notice as well.

What’s going on?

I remember from my marathon racing days that at about 18-20 miles I would hit a psychological low. I would be dragging my feet, having lost my motivation to make a new personal best, struggling with my rationalizations that I should just quit, even vowing to myself to never again engage in this idiotic effort. But then I would pop something sweet (called Goo) into my mouth, and literally within a minute or two I would undergo a radical change: full of energy, motivated to pick up the pace, almost euphoric—I would sprint to the finish line. What an exhilarating experience! I didn’t waste any time registering for the next event.

Was it the extra shot of energy that caused the turnaround? Although this is the belief among runners, it couldn’t even begin to account for it. First, such an immediate effect could not be explained by increase in calories; sugar takes longer to get absorbed through the gut (and Goo is formulated for slow release). Second, the amount of calories could not sustain a runner for more that a mile or two; the mood-elevating effect lasted for many more miles.

In a recent issue of Scientific American Mind Prof. Michael Macht of the University of Wuerzburg, Germany, examines this question. He cites the classic research by Jacob Steiner of the Hebrew University of Jerusalem, which showed that a liking for sweet tastes is innate. When Steiner gave newborns a sugar solution, the babies made sucking movements, licked their lips and relaxed their faces, looking satisfied. When given a bitter substance, the babies reacted with disgust, scrunching their eyebrows together and sticking out their tongues. Psychologist Elliott Blass of U. of Mass. Amherst found that a pacifier dipped in sugar solution lessened the pain of circumcision far more then an unsweetened one. The pain suppression occurred quickly, with a maximum effect achieved in 2 minutes. (My parents did even better: they dabbed sweet wine on my lips; my screams of protest turned into an angelic smile). Whatever the case may be—the time frame of two minutes is suggestive of a brain mechanism, rather than a digestive one.

Pathways of addiction

Princeton University Professor Bartley Hoebel and his coworkers made rats sugar-dependent using a regime common to addicting rats to alcohol, heroin, nicotine, and other addictive substances: they repeated for one to four weeks a schedule of fasting and intermittent sugar availability. The rats gradually tripled their sugar intake and learned to binge on the sugar as soon as it was offered to them. In the sugar-addled brains of these rats they detected a sharp increase in the neurotransmitter dopamine, specifically in the reward system. This is exactly the response shown by animals and humans addicted to drugs. What caused this rise was not related to digestion of the sugar—it was present even when the investigators removed the sugar from the stomachs of the rats using an implanted fistula. Most likely, the rise in dopamine was related to the sweet taste of the sugar.

How can binge eating be controlled?

Certain drugs inhibit craving in addicts. For instance, the drug Naloxone is widely used in counteracting intoxication with morphine-based drugs. Interestingly, Naloxone also causes suppression of appetite. I am not familiar with any drug trial that is aimed to specifically suppress binge eating. But who needs drugs? This is like fighting fire with fire.

Stanford psychologist Christy Telch and her colleagues experimented with 44 women with binge-eating disorder. Some received no treatment (the control group), whereas others underwent so-called dialectical-behavior therapy or DBT. In this Marxist-sounding therapy the subjects learned to deal with negative emotions in ways other than eating, Over 20 sessions, a therapist explained the genesis and role of emotions and taught the women strategies for coping with stress, among other tactics.

Results: by the end of the experiment, the women who had DBT were having many fewer eating attacks than the control subjects, and 89% of those treated had stopped binge eating. Six months later 56% of the treated women were still abstinent.

Yet again, we are seeing the inextricably intimate connection between body, brain and behavior. So I am off to the kitchen for a piece of superb Scharffenberger chocolate to celebrate this axis of bliss.

Dov Michaeli MD, Ph.D is in the Biotech industry, and loves chocolate.

By Dov Michaeli MD, Ph.D

Leptin is a hormone secreted from fat cells that provides information to the brain about energy stores. If energy stores are abundant, circulating levels of leptin are high, and the brain’s response is reduced food intake. On the other hand, in the fasted state leptin levels are low, and the response is increased food intake. It had been known that the regions of the brain where leptin exerts its influence are the nucleus accumbens and the associated nerve bundles called the striatum, regions where the reward/pleasure centers are located (and are the seat of addiction as well). However, there is little or no information about how these  brain centers integrate leptin’s signal with the rewarding properties of food.

Now a group of scientists from Cambridge university in the UK provided the missing link. In a paper published recently in Science they report on a study done on a 14 year-old boy and a 19 year-old girl who suffered from a very rare condition of leptin deficiency. This condition causes hyperphagia or excessive eating and gross obesity. But when they were injected with synthetic leptin eating was reduced to about normal levels. The investigators used fMRI (functional MRI) to visualize the nucleus accumbens and striatum. They presented the subjects with visual images of food, and for control-- visual images of non-food, in the leptin-deficient and leptin-treated states. They used a 10-cm visual analog scores to rate hunger, satiety, and the “liking” of the various food images.

And the results…

What they have shown is that leptin markedly affects neural responses to visual food stimuli; the appropriate reward centers showed markedly elevated blood flow, indicating increased metabolic activity in those regions. The responses to the questionnaire rating hunger, satiety and “liking” of the food images indicated that leptin did not affect the “liking” but rather the “wanting” of food. In the leptin-deficient state, images of well-liked foods engendered a greater wanting response, even when the subject had just been fed. After leptin treatment, well-liked food images engendered this response only in the fasted state. Thus, wanting of food appears to drive the correlation between activation of the reward centers and liking.

Why is it important?

At first blush, the whole exercise looks like splitting hairs: what difference is there between wanting and liking a food? My son used to hate anything that lived in water. But when he was famished enough he wolfed down a salmon steak and asked for more. In neurobiological terms, his low leptin level told his brain: you want this fish, liking it is not an issue right now. Which reminds me of a conversation I had with an orthodox rabbi about arranged marriages. What about love, I asked. That will come after the wedding, he answered.

From an evolutionary point of view it makes a lot of sense. Roaming the Savannah in search of food after several days of fasting there is no advantage in being too choosy; just give me that piece of meat, and I don’t care where it came from. I suspect that liking a certain food is a relatively recent addition to our behavioral repertoire, after the invention of agriculture about 10,000 years ago and the availability of reliable and abundant supply of food. Before that we didn’t eat—we devoured.

Dov Michaeli MD, Ph.D is in the Biotech industry, and he really likes good food.

By Dov Michaeli MD, Ph.D

No, I haven’t become a “new age”, “positive thinking”, “psychic energy” guy. I have seen a lot of willpower, grit and optimism overcome physical limitations—but that does not correct a physical limitation. Wouldn’t a way to change the brain’s perception of pain, or alter the brain’s pathways that determine an addictive behavior be a better solution than the panoply of drugs that we addle our brain with?

Technology to the rescue

One of the advantages of living in Northern California is being plugged in to the new and emergent technologies that are all around us. Superb universities that are incubators of revolutionary ideas, startup companies budding all over the place like mushrooms after the rain, many of them folding, other going on to do great and wonderful things (heard about the latest one? It has a funny name, something like Google)—what an exciting time and place to live in.

So it was really just a question of time before somebody took a stab at exploiting the brain’s plasticity (its adaptability or capacity to change) in order to deal with medical and psychiatric problems. Indeed, several startups are already hard at work doing just that.

How do they do it?

The technique of fMRI or functional MRI measures the blood flow in different regions of the brain, and displays it on a screen. This is how radiologists can determine areas in the brain that are metabolically hyperactive (pain perception, hunger, thinking) or hypoactive (stroke, some tumors). But now, a few companies are developing ‘real-time fMRI’, which means that you can view your own brain MRI in, well, real time. And that opens up some exciting possibilities.

Remember the old EEG (electroencephalogram) biofeedback technology? Subjects would be hooked up with electrodes which measure electrical feedback across the brain. They would then use a visual representation of the brain waves to control their blood pressure, for instance, using techniques of biofeedback such as meditation or visualization. The results were encouraging but were not translated to clinical use.

The new fMRI technique actually shows the subject which areas of the brain have increased blood flow if they suffer from chronic pain, for instance. The patient lies inside the scanner and watches a computer-generated flame projected on the screen of virtual-reality goggles; the flame’s intensity reflects the neural activity of regions of the brain involved in the perception of pain. Most people can control the flame’s intensity by concentrating and using visualization techniques. One could imagine bathing the neurally active region with a soothing drug, or dousing the area with a cold liquid, the flame would wane and patient would feel relief of the pain. Amazing but true.

This is actually an old concept. Paul Eckman, a professor of psychiatry at UCSF, wrote extensively about the mutual interaction between the body and the brain. We know, for instance, that a happy thought brings a smile to our face. But he showed that conversely, using the facial muscles involved in smiling activates the pleasure/reward centers in the brain. Result: you feel happy for no reason at all. Just try smiling every morning, or singing “Oh, what a beautiful morning” when you get out of bed, and you’d be amazed at the results. I read a few years ago about an Indian man who would go out to the park, and would laugh out loud without any reason. He claimed that it put him in a happy frame of mind for the rest of the day. Soon, other people joined him. They formed a laughing club, meeting daily in the park. This laughter became infectious, and thousands of people around the globe formed their own clubs. Sounds wacky, but it works, and it has a neurobiological basis. Try it!

The possibilities are mind boggling

What else can be controlled?

• I already mentioned the craving for drugs; addiction should be eminently amenable to this technique, since it is restricted to distinct brain regions.
• Hunger and feeding control.
• Psychiatric diseases such as depression.
• Behavioral disorders, such as uncontrolled anger, fear, phobias.
• How about stroke? Recent experiments have shown that by forcing stroke patients to use their paralyzed limb rather than the functional one, they begin to regain function. Underlying this “miracle” is the capacity of the brain to adapt and generate new pathways to serve the functions of the damaged ones. One problem with these experiments is that improvement is painfully slow and uneven. It is quite plausible the visualization of the new areas, which should have increased blood flow, could improve the outcome of these experiments.

I am sure that assorted libertarians and privacy watchdogs will warn about the sinister possibilities of this kind of brain control. Frankly my dear reader, I don’t…Just smile and be happy.

Dov Michaeli MD, Ph.D is in the biotech industry and is engaged in development of pain control medication.

By Dov Michaeli MD, Ph.D

Here are the results of a survey of 1011 people 50 years old and over, conducted by the AARP.

• 94% believe in God.
• 70% believe in Hell.
• 86% believe in Heaven. Of those, 40% believe that heaven is an actual place; 47% believe it is “state of being”.
• 23% have the cake and eat it too: they believe in Heaven, but also in reincarnation. The percentage was highest in the northeast (31%) and among people in their 50’s and 60’s (in other words, boomers).

Near Death Experience

Among people believing in the afterlife there is an almost universal acceptance of Near Death Experiences or NDE as “proof”. The most common manifestations of NDE are euphoria, a bright light (sometimes at the end of a tunnel), encounters with dead relatives, or an out-of-body experience. The sense of euphoria and the bright light can be easily explained: they can be induced by reducing the supply of oxygen to the brain (hypoxia). In fact, among teenagers in search of bigger and better thrills the  ‘in’ thing is strangulation (in most cases terminated by friends, in others terminated by complete anoxia and death when the friends are distracted or intervene a bit late).

What about the out of body experience? This is a close cousin of the concept of the soul leaving the body after death. People feel as if they are hovering over their physical bodies. Polls show that 4-5% of Americans claim to have had this experience. This concept, called in Jewish tradition “Neshama Yetera” (extra soul), is on full display in Marc Chagall’s surrealistic paintings, with its floating souls hovering over their bodily ‘owners’. How to explain that?

Out of body experience                                                                                

Until recently, there was no satisfactory explanation. It was left to the realm metaphysics and mysticism. But those pesky scientists do not seem to leave well enough alone; they keep usurping the territory of faith in metaphysics, sometimes to the detriment of their own well being (just ask Socrates, Galileo, Copernicus, and many many others). Now the time of the ‘out-of-body experience’ has come.

Out-of-body experiences are associated more with tabloid newspapers, New Age Web sites, and large doses of hallucinogenic drugs than serious scientific discussion. Yet they're often reported by reputable people who suffer from migraine headaches, epilepsy, and other neurological conditions. Intrigued by such accounts, some researchers are trying to figure out how the brain creates an aspect of human consciousness so fundamental that we take it for granted: the perception that the "self" conforms to the borders of the physical body. Two papers by neuroscientists were published in the August 24 issue of Science, and summarized by Greg Miller.

Two teams of cognitive neuroscientists independently report methods for inducing elements of an out-of-body experience in healthy volunteers. Both groups used head-mounted video displays to give people a different perspective on their own bodies. Each team also drew upon the sense of touch to enhance the illusion. Although details of the experience differed, the people in both experiments reported feelings of dissociation from their bodies. The researchers say their findings will pave the way to new brain-imaging studies of body perception and could have practical applications, such as helping virtual-reality programmers design environments that make users feel as if they are really there .

For one of the studies, a team led by Bigna Lenggenhager and Olaf Blanke, both of the Swiss Federal Institute of Technology in Lausanne , asked people to stand in front of a camera while wearing video-display goggles. In one experiment, subjects saw the camera's view of their own back, computer-enhanced to create a three-dimensional "virtual own body" (see picture above). When the subjects' backs were stroked with a highlighter pen at the same time they saw their virtual back being stroked, they reported that the sensation seemed to be caused by the highlighter on their virtual back, making them feel as if the virtual body was in fact their own body.

Moreover, when the researchers turned off the video display, guided the subjects back a few steps, and then asked them to blindly return to their former position, subjects overshot the spot where they'd actually been standing and walked to a point closer to the apparent location of their virtual body.

Adopting a similar strategy to attempt to induce out-of-body experiences, Henrik Ehrsson of the Karolinska Institute in Stockholm , Sweden , asked men and women to sit in a chair and don a video headset connected to two cameras that provided a stereoscopic view of their backs. As a subject viewed his or her own back from behind, Ehrsson used two plastic rods to simultaneously stroke the subject's chest and a location behind the subject's back. Although people felt the rubbing on their chest, in the headset they could only see Ehrsson's arm moving behind their back, reinforcing the sense that they were sitting at a location behind their actual body. The experience often elicited surprised giggles, says Ehrsson, who has tried it out himself. "You really feel that you are sitting in a different place in the room and you're looking at this thing in front of you that looks like yourself and you know it's yourself but it doesn't feel like yourself," he says. "It's almost like you're looking at a dummy." Nearly all subjects reported similar impressions on a questionnaire.

Ehrsson also repeated the illusion with electrodes attached to each person's fingers to measure skin conductance, a physiological measure of emotional arousal. Then he swung a hammer in front of the cameras so that it appeared to hit the region where people perceived themselves to be. The hammer posed no physical danger, but changes in skin conductance indicated that subjects registered a threat (they also reported feeling anxious). By showing that people respond emotionally as if they were located at a position behind their physical body, the findings provide additional evidence that the subjects buy into the illusion, Ehrsson says.

What are the implications of this research?

• Olaf Blanke, the Swiss resercher, summarized it well: "Previous research has pointed to several brain regions, including the intersection of the temporal and parietal lobes, that may be involved in producing out-of-body experiences in neurological patients, Blanke says. The new illusions can be used to examine which of these brain regions contribute to which aspects of these strange experiences, and that in turn, says Blanke, could lead to a better understanding of how the brain generates a concept of self. " This is not a trivial matter: our sense of self is considered one of the fundamental components of consciousness, a trait that separates us from lower animals.
• These experiments open a new avenue of research into the mechanisms underlying a veriety of diseases that are characterized by visual and auditory hallucinations,such as schizophrenia. It could also provide a neurobiological explanation to claims of sightings of religious figures like Jesus and Mary, as well as aliens and their flying machines.
• Last but not least, it may explain yet another paranormal phenomenon. At this rate, maybe one day Religion will be stripped of its accumulated metaphysical barnacles and only its essence will survive: a code for living a moral and ethical life.

By Dov Michaeli MD, Ph.D

In my previous posting I reviewed a paper published in the New England Journal of Medicine which showed that obesity can spread among friends and family just like any infectious disease. But unlike infectious diseases, physical proximity did not count for much: obesity did not spread among neighbors. It did spread among family members, regardless of geographical location. The strongest influence on the spread of obesity was friendship, in particular mutual friendship. This was a totally unexpected finding.

The paper had some unavoidable flaws. For instance, in assessing the effect of friendship, the investigators had data on an average of 0.7 “contacts” (or friends) per case. This hardly gives a complete picture of the social network of the average person. So, at this stage I am skeptical but hope I am wrong. I hope that additional studies will corroborate the basic finding of the relationship between social contacts and disease. Why?

Our current understanding of disease

We have been educated to look for physical explanations to biological/medical phenomena. As physicians we were taught to look for the “disease genes” ( for instance Huntington’s disease, sometimes called Guthrie’s disease after the famous folk singer Woodie Guthrie who died of this disease), or the metabolic dysfunction ( diabetes type 2), or environmental influences ( lead poisoning, pollution-induced respiratory diseases), or combination of those ( cancer as a consequence of genetic predisposition and environmental mutation-causing substances). We viewed with suspicion the ancient art of ‘alternative medicine,’ in my view justifiably so. When subjected to rigorous scientific examination, most if not all of those folk remedies turned out to be just, well, folktales.

But ‘hard science’ Medicine is also wanting, and the example at hand is the spread of obesity. Several genes that predispose to obesity have been identified, but they account for only a minority of cases of the ‘disease’. What accounts for the rest? We all answer reflexively: lifestyle. But that’s too glib. Why do some people have to fight mightily to avoid obesity, while others barely move off the couch with nary an ounce of weight gain? Again, metabolic differences sometimes exist, but many times they are at least not readily apparent.

Enter social networks

The surprising finding that friendships are powerful factors in the spread of obesity, if corroborated, would go a long way toward explaining the puzzle of the ‘obesity epidemic’. And not only obesity: many other diseases are now becoming susceptible to this analysis. Why is it that we are having an ‘autism epidemic’? Why is it that certain school districts have an inordinately higher prevalence of autism? No suspected physical agent, including the much abused vaccination of children, stood the test of rigorous examination. Increased awareness? Erroneous or loose diagnoses? They don’t account for the rise.

The possibilities are even more amazing. If you examine the genes of obesity and diabetes type 2, you’d find that these two diseases share at least three genes. Which raises the possibility that there exist networks of diseases, all interlinked. This may explain, at least in part, why a certain drug given for disease A would affect disease B, or cause side effects unforeseen by our knowledge of the drug’s mechanism. A wonderful example is the drug imatinib (or Gleevec), designed to work specifically on a mutation of the enzyme tyrosine kinase (called Bcr-Abl) that causes CML or Chronic Myelogenous Leukemia. Lo and behold, despite its great specificity it turned out to inhibit another tyrosine kinase called c-kit, that is responsible for rare a stomach cancer called stromal tumor. What’s the connection? The drug action uncovered an unsuspected close link between the two enzymes; both evolved from a common ancestor gene, and the two cousin proteins resemble each other like twins. But wait, there is more... even more unexpectedly, it was discovered that the drug activates a certain immune cell (IKDC) that is active in killing infectious organisms and tumor cells. The mechanism for that is largely unknown. This is only one example, but it hints at as yet- undiscovered complex networks of diseases.

Question: all these examples deal with molecular networks, which makes it intuitively easy to visualize interactions between molecules and the effect of these interactions rippling through the networks. But how would something spread through social networks? The answer: through memes.

Memes, and spread of ideas (and diseases)

What is a meme? The definition I like the best is from the Wikipedia:

meme , (IPA: /mi:m/ ) as defined within memetic theory, comprises a unit of cultural information, cultural evolution or diffusion that propagates from one mind to another analogously to the way in which a gene propagates from one organism to another as a unit of genetic information and of biological evolution. Multiple memes may propagate as cooperative groups called memeplexes (meme complexes).

Biologist and evolutionary theorist Richard Dawkins coined the term meme in 1976. in his book “ The Selfish Gene”. He gave as examples tunes, catch-phrases, beliefs, clothing fashions, ways of making pots, and the technology of building arches.

Amazing; units of cultural evolution spread like genes or viruses, which like genes, are packets of DNA or RNA, and obeying Darwinian laws. No wonder we use such phrases as “an infectious idea” or “the virus of extremism”. Or here is David Brooks of the New York Times on the subject of naming newborns:

“Naming fashion doesn’t just move a little. It swings back and forth. People who haven’t spent a nanosecond thinking about the letter K get swept up in a social contagion and suddenly they’ve got a Keisha and a Kody. They may think they’re making an individual statement, but in fact their choices are shaped by the networks around them. “

Well, networks networks everywhere… from the molecular level, to the cellular level, to whole organisms, to social units, to nations, to the whole human race. I remember reading in the early 70s the essays of Lewis Thomas, “Notes of a biology Watcher”, published periodically in the New England Journal of Medicine. It was poetry in science, and science in poetry. This is from his introduction to the collection of his essays, “The Lives of a Cell”:

“Viewed from the distance of the moon, the astonishing thing about the earth, catching the breath, is that it is alive”. And later: “It has the organized, self-contained look of a live creature, full of information, marvelously skilled in handling the sun”.

In today’s less poetic terminology we could call this earth-creature 'an infinitely interconnected complex networks'.

The battle of the memes

Memes, like genes, spread among people, only they do it a lot faster. The idea of agriculture, invented in Anatolia (today’s Turkey ) about 10,000 years ago, spread all the way to the Iberian Peninsula within 2000 years. This is lightening speed, considering that a new mutation would need hundreds of thousands of years to establish itself in a given population. Or take the meme of the industrial revolution: within 100 years industry spread throughout the ‘industrial world’ of today. Or the computer, or the iPhone, or… what’s the next meme to spread like a virus throughout the world?

But not all memes are created equal. Like genes, they have to be accepted by the individual’s mind, and if need be demolish competing memes. An example: the idea (or meme) of monotheism, displacing polytheism that had reigned supreme for thousands of years. What was needed for it to triumph was the cultural readiness to be accepted. The early Christians were mocked, tortured and fed to the lions. But with time they became tolerated, tacitly accepted, and finally, following an approval from an authority figure ( Emperor Constantine , 312 A.D.), the whole Roman Empire converted. Mind you, the people did not have to be coerced—they were ready, the meme of Christianity had already infected them.

What does all that have to do with obesity?

Just like many other memes, the beginning of the obesity meme may have been hard. The sight of an obese person clashed with the body image of most people. An obese woman in shorts? Unheard of! With time, with more and more obese people in shorts and swim suits it ceased to be novel; in fact, it became sort of accepted. And the road from acceptance of obesity to the powerful influence of an obese friend on his close friends to become obese is quite short, and plausible.

Why doesn’t it work in the other direction, you might ask? Why doesn’t the thin person influence his or her obese friends? I think the answer lies in the biology. Our metabolism is geared toward storage of energy as fat. To go the other way is energetically (in the metabolic sense) and psychologically an uphill battle. So in the battle of the memes, obesity wins because biology is on its side.

Are we doomed to everlasting obesity?

A perfect example of how to win the battle of competing memes is the reversal of the smoking epidemic. Education and peer pressure rendered our mind ‘unready’ to accept smoking despite its addictive properties. Intensive education, coupled with unrelenting peer pressure and regulation can form a countervailing force to resist the path of least resistance offered by the biology.

Will it work? There are encouraging signs . There is a website, http://www.peertrainer.com/, that brings together people who are trying to lose weight, and even more difficult--to maintain it. The whole premise is for the members of this network to publish daily their diet, their elation at success and the heartbreak of failure. The other members of the network are supportive, cheering on, encouraging, and when appropriate--dispense some tough love. Judging from the enthusiastic testimonials and almost fanatical belief in the network's help--it works. Yes, these are still testimonials, but to paraphrase senator Everett Dirksen, a testimonial here, a testimonial there, and pretty soon you are talking  real sample.

Epilogue

So here we are , at the end of our journey through biological networks, linked to social networks, and then completing the circle in the biological network again. I fervently hope that it will turn out to be true. Wouldn’t it be wonderful if the World-Wide Web assumed a new meaning, that of a brand new vision of life on earth? All interconnected, all intimately dependent on all. 

Dov Michaeli MD, Ph.D. is in the Biotech industry and has an abiding interest in all things biological.

We modern humans have a tough time curbing our appetite. The reason for that is that our primitive ancestors, leading a life of hunters/gatherers (or scavengers, as recent research suggests) did not have a steady, predictable supply of food. So our physiology has evolved to store calories when we could get them, in the form of fat. The need was to maximize conservation of energy (or calories), and an elaborate system has evolved in the gut and the brain to accomplish that.

This state of affairs served our species well until relatively recently. When the industrial revolution arrived about 200 years ago, farms became more efficient and produced more food, people became more affluent working in factories and offices, being able to afford the cornucopia of food and drink. At the same time work, and life in general, demanded less and less effort (or expenditure of calories).The consequences are evident today on every street of the industrial world. Unfortunately, our metabolism has not been able to adapt to this relatively recent change in lifestyle. Such things require an untold number of genetic mutations and take thousands of generations.

Is there nothing to be done about it?

The only way we can change our metabolism is through drugs. So far, all the heavily promoted and hyped diet pills, which are basically attempts to change our metabolism chemically, have been either very limited successes, or total failures. Fortunately, we are a species endowed with a high degree of awareness and the capacity to quickly adapt through changes in behavior. Remember Pavlov’s drooling dog? We are better. Being aware of what triggers our brain to send ‘hunger’ signals allows us to counteract them through behavioral strategies.

The biological clock

No, this is not really a ticking clock; but, biologically speaking, a lot more powerful. A clock is neutral, it just keeps time. There is no inherent functional meaning to 3AM or 3PM. It is us who invest it with the meaning of afternoon or early morning. The biological clock, on the other hand, doesn’t only tell time, it gives time a meaning. For instance, around 6 PM I get terribly hungry. Or around 6:30 AM I wake up regardless whether I got enough sleep or not. And when I travel across time zones, either to Europe or the Far East, my biological clock and my whole physiology still lives in California, and is totally screwed up.

We can see then, that this clock actually controls much of the brain function. One of these functions is the sensation of hunger. I am used to eating breakfast at a certain time of the day, and if I don’t get it I feel that something is missing, I am unhappy and miserable to be around, I can’t function at peak performance. If you think about it, the clock didn’t just control hunger, it controlled mood (great omelet--happy; it’s 11 AM and I haven’t had my breakfast yet--unhappy).

The nice thing about this all-powerful clock is that it can be trained to suit our whims. Try skipping lunch and the first few times will send you trawling for food the whole afternoon. But after a while, your need for lunch becomes less and less urgent until eventually you really don’t feel the need to eat in the middle of the day. But don’t carry it too far. I am reminded of one of my professors at UC Berkeley ( who will remain anonymous for obvious reasons), who studied the metabolic effects of calorie deprivation in the German cockroach (Blatella germanica; and I am not making this up). He slowly habituated the critters to a progressively lower calorie diet. One morning he came to the lab and was dumbfounded to find his meticulously habituated cockroach colony totally, irreversibly dead. Theories as to the causes ranged from the sublime to the ridiculous. To my simple-minded suggestion that they may have died of run-of-the-mill starvation, he responded plaintively,” but they have already got used to it…”.

Sight and smell

Why are the French such foodies? My theory de jour: it’s the presentation. When we walked in the market in Beijing and saw row after row of hanging Peking ducks at the butcher shops, I was mildly disinterested. But when they wheeled in the duck in a fancy restaurant the thing looked irresistably delicious and we devoured the whole thing. How do you think did Ray Croc make McDonald’s such a success? He stood outside a small hamburger diner and took in the smells. He immediately knew that he stumbled upon a winner, bought the restaurant and its formula for Freedom (aka French) fries and hamburger patties, and the rest is, as they say… fat kids with diabetes. Both the rhinencephalon (or the smell center) and the visual cortex communicate with the hypothalamus, the area in the brain that controls hunger, through extensive neural connections.

Don’t eat when you are cold

One of the important functions of our physiology is to maintain normal body temperature. For instance, the shivering response to cold is a way for the body to raise its temperature. Metabolism creates heat, and when we are cold the normal response is to eat more, and more frequently. That’s why we tend to eat more in the winter (and, alas, gain more weight) than in the summer. Can you imagine yourself being ravenous on a 100° day? All I can think of is crushed-ice margaritas.

What can we do?

The answer is: a lot. The biological clock and the relationship between smell, sight and hunger are all subject to habituation, or more plainly—to our will. This is literally the old 'mind over body', and all we need is the will and the persistence.

And yes, don’t forget to heat up the house before you sit down to dinner.

Dov Michaeli MD, Ph.D

We were watching tonight a great program on PBS about Billie Jean King and her wonderful tennis career. Her 1973 match, or dare I say grudge match, against Bobby Riggs, was a delight to the eyes and the soul. We relished her strategy of running ragged this aging fool from one end of the court to the other. There she was: a skilled, rebellious young woman facing a male chauvinist who taunted her to test her mettle against his. But the match had a much larger meaning; it was emblematic of the new generation, of a new world upending the old order and its tired prejudices, not in a bloody revolution fought in the streets—but in a fair, civilized match on the tennis court. How many of you remember a single feminist demonstration? but we all remember this historic match; such was its impact.

However riveting her life story was, what caught my attention was her secret weapon: her tremendous ability to focus, to remain calm under pressure, in fact to relish stressful situations. As she herself said, minutes before a match all her anxieties and insecurities would be replaced by determined calm and focused planning. How could she do that?

It’s all in your head

The neurons in our brain talk to each other through chemicals that are called neurotransmitters. One of those is called dopamine, and its function is invaluable; when we have a pleasurable experience of any kind, dopamine is released. We thus learn to associate this experience with reward and pleasure and tend to repeat it. This is important to our brain’s unconscious decision- making. Just think of it: if on every occasion that we encountered a delicious meal, or a glass of wine, or making love, we had to gingerly try it first to see if we liked it—we would be paralyzed with indecision. Billie Jean King did not have to convince herself that she loved the game every time she stepped on the court—her brain had already made this decision for her.

What happens when dopamine levels in the blood are elevated?

The physiological and psychological effects of elevated dopamine are wonderful: a sense of optimism, exhilaration, even euphoria; a sense of increased energy that can escalate to hyperactivity, sleeplessness, loss of appetite, increased heart rate and hyperventilation. As part of this behavioral complex, there are a few other traits: extremely focused attention, motivation and goal-directed behavior. Do you recognize these as ‘symptoms’ of falling in love? Can the pounding heart be the reason for the association of love with the heart? Can it explain the rapt attention of the young lover earnestly listening to her mate’s nonsense?

What about Billie Jean’s uncanny ability to focus on the game? She loved the game, she was in love with it. And I’d bet her dopamine levels were sky high as well.

It is a cliché that love made the world go round. Unfortunately, my friend, I hate to disillusion you—it’s all in the dopamine.

Dov Michaeli MD, Ph.D

Genes

In 1993 scientists reported on a Dutch family, 14 members of whom were sociopaths, involved in aggressive crimes such as bullying, physical violence, rape, and arson. They all had in common a mutation in a gene that makes an enzyme called MAOA. The function of this enzyme is break down neurotransmitters such as serotonin and noradrenaline (or norepinephrine, a chemical first cousin of adrenaline). The ready conclusion was: defective enzyme caused elevated level of serotonin and noradrenaline, resulting in overactive brain circuits that serve aggressive behavior.

Case closed? Not so fast…

In a wonderful summary of the topic in Newsweek magazine ( April 30, 2007 ) one of my favorite writers on the subject, Sharon Begley) describes a 2002 study in New Zealand of 442 men who were followed since their birth. Indeed, men with low MAOA were more likely to engage in persistent fighting, bullying, cruelty and violent crime. But not all of them; only men who had been neglected or abused as children fit the bill. Men who grew up in a normal environment exhibited none of the violent traits.

Neuroanatomy

In previous postings we waxed scientific about the amygdala, two almond-shaped structures deep inside the brain, that are the seat of primitive emotions such as rage and fear; these constitute the emotional basis of the fight or flight reaction, which is mediated by noradrenaline. These waves of seemingly overwhelming emotions are checked and inhibited by another, more modern structure in the brain: the prefrontal cortex. This structure is the seat of judgment, planning, abstract thinking. It inhibits inappropriate or impulsive behavior, and is engaged in constant self-monitoring (could it be the anatomical seat of the Freudian super ego?). So in typical Ying/Yang fashion, the outcome of our behavior must then be the product of the amygdala and prefrontal interaction. Remember the then famous case of Kip Kinkel, a 15 year old who in 1998 killed his parents and two dozen schoolmates in Springfield , Oregon ? His brain scan showed a completely silent prefrontal lobe; he had nothing to check and balance his raging anger emanating from his amygdala.

Is this it? Not quite…

Hormones

Women love to point out, without much evidence I might add, that men’s aggressive behavior can be traced to their testosterone-addled brain. Only partly true. The level of testosterone is within normal limits between 20% and 200% of the mean; that’s a huge range of normal. However, if the level of testosterone exceeds 400% of the mean, then indeed women are right—men with these levels are more prone to violence. In fact, testosterone is an equal opportunity hormone; in a species of hyenas (I forget which) the first newborn in a litter, be it male or female, will eat the rest of the brood within days of birth. It turns out that this vicious sibling has inordinately high levels of testosterone in its brain, much higher then the other hapless siblings.

But to assume that we are simple automatons, following helplessly the script written by our genes, brain circuits and hormones, would deny a self evident fact—we don’t behave automatically, we do have a certain degree of free will.

Psychology

The interaction of biology and the life one leads turns out to be of paramount importance in shaping the criminal mind. The most important characteristic of the behavior of mass killers is paranoia. They have the sense that the whole world is against them, that everybody but themselves is responsible for their troubles, that the world is unfair. They are usually depressed and socially isolated.

This kind of personality, you might say, could be the product of brain circuitry gone awry. But here is a fascinating finding from animal and human studies: behavior can change brain circuitry and function-- an outstanding example of nature/nurture interaction. So what are the non-biological roots of violent behavior? We finally arrive at the inevitable:

Society and culture

It is the social environment that allows, indeed encourages, psychopathic criminal behavior. Many societies have members with genes gone awry, with malfunctioning brain circuits, with males suffering from raging hormones, with children raised in violent homes. But, sad to say, we have the dubious distinction of being the champions of gun violence in the civilized world. In 2004 there were 29,645 deaths due to gun violence in the US , or 10.08 per 100,000. For comparison, France had 4.93, Belgium 3.67,and Spain 0.75 per 100,000.

In 5 years of war in Iraq about 3200 of our soldiers got killed. Yet, we tend to see the situation in Iraq as intolerable but we dismiss  the carnage in our own streets with a helpless shrug: "It’s the culture… "

We mentioned the case of Kip Kinkel. Yes, his prefrontal lobe did not do its job. But here is rest of the story: a psychotherapist actually suggested that his dad buy him a gun so they could have something to do together.

As Pogo said: we have met the enemy, and it is us.

Dov Michaeli MD, Ph.D

A few weeks ago, a fascinating story about the effect of the mind on physical well-being was widely published in the newspapers. A group of hotel room maids received a physical exam and were told that their work, making beds, cleaning baths, and vacuuming rooms is equivalent to daily moderate exercise and is good for their health and fitness. Another group of maids, in another hotel, received the physical exam only. Three weeks later, the maids who had been told that they were in good physical shape reported feeling in good health, had a low rate of absenteeism, and reduced their blood pressure from the initial exam. None of these were evident in the control group. Impressive, but hardly compelling. The usual criticisms of small groups, non-random selection, the short observation time—all these are real experimental issues, and “more studies are necessary” is the usual caveat following such experiments.

Enter the immune response.

During the last two decades sporadic reports were published in the scientific literature, claiming that both in animals and humans, state of mind had a significant effect on immunity. Stress in animals suppressed their immune response and increased their susceptibility to infection and cancer. Similar results were shown in humans, albeit under less controlled conditions.

Now comes a report in the April issue of the Journal of the American Geriatric Society, by Drs. Irwin and Holmsted of UCLA and Dr. Oxman of UCSD. They examined the effect of tai-chi on elderly people’s immunity to shingles, caused by a virus called varicella zoster.

The randomized, controlled clinical trial included 112 healthy adults ages 59 to 86 (average age of 70). Each person took part in a 16-week program of either Tai Chi or a health education program that provided 120 minutes of instruction weekly. Tai Chi combines aerobic activity, relaxation and meditation, which the researchers note have been reported to boost immune responses. The health education intervention involved classes about a variety of health-related topics.

After the 16-week Tai Chi and health education programs, with periodic blood tests to determine levels of VZV immunity, people in both groups received a single injection of VARIVAX, the chickenpox vaccine that was approved for use in the United States in 1995. Nine weeks later, the investigators did blood tests to assess each participant's level of VZV immunity, comparing it to immunity at the start of the study. All of the participants had had chickenpox earlier in life and so were already immune to that disease.

Tai Chi alone was found to increase participants' immunity to varicella as much as the vaccine typically produces in 30- to 40-year-old adults, and Tai Chi combined with the vaccine produced a significantly higher level of immunity, about a 40 percent increase, over that produced by the vaccine alone. The study further showed that the Tai Chi group's rate of increase in immunity over the course of the 25-week study was double that of the health education (control) group. The Tai Chi and health education groups' VZV immunity had been similar when the study began.

In addition, the Tai Chi group reported significant improvements in physical functioning, bodily pain, vitality and mental health. Both groups showed significant declines in the severity of depressive symptoms.

Is this study convincing?

The study was well-designed, well-controlled and carefully executed. It is the first study in humans that lends credibility to the notion that our immune response is controlled by the brain. This study is a harbinger of more serious studies, not only demonstrating the mind/body connection, but also the physiological mechanism by which this is accomplished.

Is the day when we could will ourselves to better health far off? How exciting!

Dov Michaeli MD, Ph.D