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Epigenetics: the hidden switches of the mind / Eric J. Nestler

Life experiences may trigger mental illnesses in a surprising way: they create "epigenetic" changes in the brain that turn genes on and off without changing the genes themselves 

Epigenetics, from the website
Epigenetics, from the website

Matt is a history teacher. His twin brother, Greg, is a drug addict. (The names have been changed to avoid identification.) The boys grew up in the Boston area and did well in high school: they were good students, did well in sports and got along well with their friends. Like many young people, the brothers sinned here and there with beer or cigarettes, and also with marijuana. When they got to college, they experimented with cocaine. Greg, this experience derailed you.

At first, he was able to function normally, attend classes and maintain relationships with friends. But soon the drug was the most important thing in his life. Greg dropped out of school and worked several simple jobs in grocery stores and fast food restaurants. He rarely lasted more than a month or two and was usually fired for being absent too much or arguing with clients and co-workers. His behavior became more and more unpredictable - sometimes violent - and he was arrested time and time again for stealing to finance his addiction. All his rehabilitation attempts failed, and at the age of 33, when a court sent him to be evaluated in a psychiatric hospital, Greg Der Rehov was helpless: cut off from his family and enslaved by his addiction.

What made Greg so sensitive to the siren song of cocaine, that the drug ruined his life? And how was his twin brother, who shares exactly the same genes with him, saved himself from a similar fate? How does it happen that certain people who are exposed to a drug are condemned to lifelong addiction, while others can throw the memories of youth behind them and continue with a full and fruitful life?

These questions are not new, but neuroscientists are beginning to develop a new approach to finding the answers, and they are using discoveries from other fields to do so. In the last ten years, as part of the biological research on the development of the embryo and on cancer, an extensive set of molecular mechanisms has been revealed that allow the environment to change the behavior of genes without changing the information they contain. The genes do not undergo mutations, but "epigenetic" changes that affect the level of activity of the gene. These changes can sometimes be fixed for life.

In my lab, and in other labs working in the field, we are now discovering signs that epigenetic changes caused by drug consumption or constant stress change the way the brain responds to experience: whether in the ability to quickly recover or in succumbing to addiction, depression, or other psychiatric disorders. Although we are only in the early stages of understanding the molecular interplay between genes and the environment, we hope that what we learn will lead to improved treatment of these difficult situations, and perhaps even to new insights into how mental illnesses are transmitted from generation to generation.

beyond the gardens

Our studies of epigenetic influences on mental illness fill the void left by decades of early research into the genetic roots of addiction, depression, autism, schizophrenia, and other psychiatric disorders. As in many medical conditions, these neurological injuries also have a strong hereditary component: about half of the risk of addiction or depression is genetic, and it is higher than the genetic risk of high blood pressure or most types of cancer. But genes are not the be-all and end-all. As we saw with Greg and Matt, even identical genes do not guarantee that two people will develop the same disease. Environmental signals, such as exposure to drugs or stress accelerate the onset of psychiatric problems in people with a genetic predisposition to it. And sometimes, even random molecular events that occur during development can affect the outbreak. No two people have exactly the same experiences or the same developmental history.

The question is therefore: what is the mechanism leading to mental illness induced by environmental signals? On one level, the answer is clear: nature and environment meet in the nerve cells of the brain. These cells process everything we experience - watching a movie, hugging, smoking cocaine or thinking about dinner - and then share the information with each other through the release and recognition of substances called neurotransmitters. A neurotransmitter can activate or suppress individual nerve cells and turn many different genes on or off. Identifying the genes it affects A particular will help determine how a nerve cell will respond to an experience that will ultimately shape the person's response to that experience.

Most of these effects last a short time. For example, exposure to cocaine will activate the reward center in the brain and cause a transient euphoria. This feeling soon fades, and the system returns to normal. It is not yet clear how drugs, stress, or other experiences can create long-term effects and cause a person to succumb to depression or addiction. Here, many neuroscientists believe, epigenetics comes into play.

Give them signs

To understand why epigenetics has attracted our attention, you need to know a little about the way genes are regulated. A gene, in a simple definition, is a section of DNA that usually defines the composition of a protein. Proteins carry out most of the processes in cells and thus control the behavior of the cell. DNA is not randomly distributed within the cell nucleus; It is wrapped around clusters of proteins called histones - like a thread on a coil - and continues to fold into structures called chromosomes. The combination of protein and DNA in chromosomes is called chromatin.

The packaging of the DNA in this way maintains order in the nucleus, and mainly helps to control the behavior of the genes. When the packaging of the genes is tighter, access is prevented from the mechanism that activates them, and they tend to be in an inactive state. In a nerve cell, for example, genes that code for liver enzymes are pushed into tightly packed regions of chromosomes. When the gene is needed, the section of DNA where it resides opens up a little, and then the gene becomes accessible to the mechanism that copies the DNA into a strand of RNA. In most cases, the same RNA will then be used as a template for the production of the coded protein. Stimulation of a nerve, for example, may cause the cell to increase the transcription of the genes that contain the code for creating certain nerve messengers, which will lead to an increased build-up of these communication molecules in the nerve cells.

A section of chromatin will be relaxed (ready to be activated) or compacted (off temporarily or permanently) depending on epigenetic marks: chemical tags attached to histones or to the DNA itself. These tags can take different forms and together create a kind of code indicating how tight the chromatin should be and if the genes at its base should be transcribed [see box on the right]. A certain gene may be more active, or less active, depending on the marking on its chromatin.

Epigenetic modifications are carried out by a variety of enzymes, some of which attach chemical tags and others remove them. Charles David Ellis from Rockefeller University, one of the leaders in the field, called these enzymes, responsible for the epigenetic code, "writers" and "erasers". For example, the enzyme histone acetyltransferase, which binds the chemical group acetyl to the histone protein, is "writing", while the enzyme histone deacetylase, which removes this mark, is "erasing". These epigenetic marks attract other proteins that act as "readers". Readers bind to specific epigenetic tags, and can loosen or compact the chromatin in the region of the tags by recruiting other regulatory proteins, which stimulate or repress transcription of local genes. Histones to which many acetyl groups are attached, for example, attract readers that open the chromatin and other proteins that promote gene activation. Conversely, histones with many methyl groups attract readers that can either repress transcription or stimulate it, depending on the exact location of the methyl marks. [For more on the methylation process and its discovery, see the spotlight article with Professor Haim Sider on page 14 of this issue.]

The environment can influence gene activity in regulating the behavior of epigenetic writers and erasers - and thereby influence the labeling, and the rebuilding, of the chromatin. Sometimes the tags stay on for only a short time, it is said, to allow a neuron to respond quickly to a strong stimulus by producing a sustained wave of neurotransmitter release. And sometimes, the tags remain in place for months or years or even the entire life of the organism: strengthening or weakening the neural connections involved in storing memories, for example.

The addition and removal of acetyl and methyl groups, and other markers, can help the brain respond and adapt to environmental challenges and experiences. But my lab and other labs are now finding in animal studies that these beneficial epigenetic processes can go awry in conditions like addiction and depression, where disrupting the normal set of changes can create intense cravings, instill feelings of failure, or otherwise trigger an animal's propensity for a lifetime of undesired behavior. standardization. Examination of postmortem brain tissue suggests that the situation may be similar in humans.

prone to addiction

The findings regarding addiction build on previous studies that examined how addictive drugs take over the brain's natural reward center. Many studies have identified, for example, extensive changes in gene activation in response to cocaine, opiate drugs, or other addictive substances. Some of these changes in gene "expression" remained even after months of abstinence, and the researchers had difficulty finding the mechanisms that cause this fixation. To try and explain the long-term effects of epigenetic changes, my lab began about ten years ago to examine whether cocaine can change the activity of genes in the brain's reward center by changing their epigenetic tagging. Cocaine is a strong and addictive drug, in animals as well as in humans, so it is possible to examine its long-term effects under laboratory conditions.

One dose of cocaine causes extensive and stable changes in gene expression, as can be seen from messenger RNA concentrations - which are a direct measure of gene activation. An hour after mice receive their first injection of cocaine, nearly 100 dormant genes are activated. Even more interesting is what happens when the animals are constantly exposed to the drug. A handful of the genes that are activated upon initial exposure to cocaine are silenced when the exposure becomes daily. These genes cease to be sensitive to the drug.

But a greater number of genes do the opposite: they are activated temporarily in response to the initial exposure to cocaine, but constant exposure to the drug increases their activity levels even more - in some cases for weeks after the last injection. Moreover, these genes remain particularly sensitive to cocaine even after a prolonged period of non-exposure to the drug. That is, constant use of cocaine prepares these genes for future activation and allows them, in effect, to "remember" the rewarding effect of the drug. This is where the roots of drug relapse and addiction among drug users lie. It turns out that the high sensitivity is due to epigenetic changes in the genes.

Using sophisticated methods to catalog the epigenetic marks across the entire mouse genome, we were able to show that constant exposure to cocaine selectively changes the array of acetyl and methyl tags on hundreds of genes in the reward center of the brain. All of these changes tend to loosen the chromatin structure, and as a result, the genes become more accessible for activation when exposed to cocaine. Again, many of these changes are temporary - they pass after a few hours. But some of them remain for a long time: we have documented changes that remain in place for at least a month, and we are starting to look at even longer periods.

We are also beginning to understand the mechanisms that create the permanent changes over time. In our laboratory we found that constant exposure to cocaine suppresses the activity of some of the erasers that remove acetyl groups, as well as of certain writers that add inhibitory methyl groups. Chromatin with more acetyl groups - or fewer methyl groups - remains more open, and the genes in it are more exposed to activation. Constant exposure to cocaine also affects the activity of other writers and erasers in the reward center of the brain, leaving behind a group of epigenetic marks that increase the accessibility of genes for activation. In support of this observation, we found that when we artificially stimulate the activity of these writers and erasers to mimic the effect of constant drug consumption, without administering the drug itself, the animals become more sensitive to the pleasure effect of cocaine—one of the hallmarks of addiction.

The changes in the activity of writing and erasing following constant use of cocaine also remain over time, which may explain the long-term changes in the activities of the marked genes - and the way the animal will respond to future experiences. Because the reward center of the brain responds to such a wide range of stimuli - including food and sex - changing the activity of the nerve cells in the reward center can fundamentally change the animal's behavior.

marked for depression

Neural adaptations that affect long-term behavior are also at the root of a common and extremely difficult chronic psychiatric condition: depression. As with addiction, different aspects of this disease can be studied in animals. In my lab, we work with mice that are exposed to constant social defeat. Easy-going mice are paired with more aggressive partners. After ten days of repeated assaults, the submissive mice show many signs of depression: they stop engaging in pleasurable activities (sex, eating sweets), and they become anxious, withdrawn and less adventurous. They can even eat to the point of obesity. Some of the changes last for months, and can be alleviated by regular administration of anti-depressants used to treat humans.

When we looked at the DNA of the mice, we saw epigenetic changes in about 2,000 genes in the reward center of the brain. In 1,200 of these genes, we measured an increase in a particular epigenetic mark: a form of histone methylation that suppresses gene activity. It therefore seems that depression may turn off genes that participate in activating an area of ​​the brain that makes the animal feel good, and it creates a kind of "molecular scar". We found that treatment with imipramine, a common anti-depressant drug, for a month restored many of the changes caused by stress. Similar epigenetic changes were found in brain samples taken from people who were depressed at the time of their death.

Although depression is a common phenomenon in humans, not all people are equally vulnerable. We found the same to be true in mice. About a third of the males who received a daily "dose" of social defeat do not become depressed. Despite the constant harassment, they do not show withdrawal or passivity like the other members of their group. The resistance is also evident in their genes. Many of the epigenetic changes we see in the depressed mice do not appear in the resistant mice. In the resistant mice, a group of additional genes were found in the reward center, in which there are epigenetic changes that are not evident in the depressed animals. The findings suggest that the alternative pattern of changes protects the brain, and that resilience is more than the absence of vulnerability - it involves an active epigenetic program that can be called upon to combat the effects of chronic stress.

We also found that the set of epigenetically modified protective genes in resistant mice includes many of those whose activity returns to normal in suppressed mice after imipramine treatment. A subset of these genes is known to increase activity in the reward center of the brain, and therefore as an antidepressant. These observations raise the possibility that antidepressants in humans work, in part, by activating some of the same epigenetic protective programs that operate in people who are not prone to depression. So, in addition to searching for drugs that will block the bad effects of chronic stress, we may also be able to identify drugs that will strengthen the brain's natural resistance mechanisms.

A mother's legacy

We have seen that the effects I have mentioned so far can last for a month, the longest period we have tested. But epigenetic changes can trigger lifelong changes in behavior, as Michael Meaney of McGill University and his colleagues have demonstrated. Mini examined the effects of maternal care on epigenetic changes and the future behavior of the offspring.

The researchers observed the rats, and saw that some mothers take care of their pups with great devotion. others are less diligent. The offspring of the active mothers are less anxious and produce less stress hormone in response to disturbance compared to puppies whose validations were more relaxed. Moreover, females raised by devoted mothers become devoted mothers themselves.

Minnie's group went on to show that the effects of maternal behavior are, at least in part, through epigenetic mechanisms. The researchers tested sequences that regulate the activity of the gene that codes for the glucocorticoid receptor - a protein found in most body cells and mediating the animal's response to the stress hormone cortisol. They found more DNA methylation in this region in puppies raised by neglectful mothers than in puppies that received diligent care. The increased methylation, found in the hippocampus, a brain region involved in learning and memory, causes neurons to produce less of the receptor. Since activation of these receptors in the hippocampus signals the body to slow down cortisol production, the epigenetic reduction in the number of receptors exacerbates the stress response in the animals and makes them anxious and fearful, traits that remain throughout their lives. The effects on the glucocorticoid receptor may be only part of the story. Frances Champagne of Columbia University and her colleagues found similar epigenetic differences in the genes that code for the estrogen receptor between puppies raised by hardworking mothers and puppies raised by lax mothers. It is therefore likely that it will be discovered that epigenetic marks of many other genes are involved in programming the responses to something as complex as maternal behavior, and consequently in its inheritance.

It therefore appears that epigenetic changes that apply to a gene in one generation can, in fact, be passed on to the next generation, even if the changes are not transmitted through the sex cells. The mother's behavior changes the epigenetic regulation of genes in the pup's brain, then the pup grows up and behaves in the same way, and as a result the epigenetic marks and behavior in her pup change, and so on.

Epigenetic healing

In the coming decades we will face the challenge of using what we discover about the relationship between epigenetic changes and behavior to develop improved methods for treating various psychiatric disorders. Our lab and other labs have found that drugs that preserve the acetyl groups on histones by inhibiting the enzymes that erase these marks have a strong effect on depression. Moreover, although narcissistic mothering is linked to changes in DNA methylation, Minny found that the same drugs can encourage devotional behavior (because increased acetylation can counteract the suppressive effects of hypermethylation).

Although these results are promising, it does not appear that the inhibitors on the market today will be useful in the fight against mental illness. The acetyl erasers, enzymes of the histone deacetylase type, regulate the epigenetic marking in cells in the brain and throughout the body, therefore substances that neutralize them without diagnosis may lead to serious side effects. One possibility would be to develop a drug that would selectively inhibit such enzymes in the areas of the brain most affected in certain psychiatric conditions - the reward center, for example. Another possibility would be to identify new proteins involved in epigenetic changes in the brain alone. But in the end, the best approach may be to determine which genes undergo epigenetic changes in depression or addiction: the genes for neurotransmitter receptors or specific signaling proteins involved in neural activation. Then we can focus our efforts on designing drugs that will act directly on the activity of those genes or on the activity of the proteins they produce.

Pass it on

An important question that remains unresolved is to what extent the epigenetic changes associated with neuropsychiatric disorders are heritable. In experiments of sorts, rats "inherit" certain behavioral patterns and the accompanying epigenetic profiles. But these changes, which are directly affected by behavior, occur in the brain. They are not transmitted through signs on the genes in the gametes that create a new embryo. A more fascinating question is whether such experiences can cause epigenetic changes in sperm and egg cells, which can be passed directly to the offspring.

It is not unreasonable to think that chronic arthritis or an addictive drug can change the activity of the genes in the sperm cell or the egg cell; Stress hormones and drugs are not limited to the brain, but flood the entire body, including testicles and ovaries. But what is difficult to understand is how such a change in sex cells can be maintained over the generations. The acquired epigenetic changes are erased during cell division of the type that produces sperm and egg cells. Also, how will these changes, if they do exist in the fetus, be reflected in their effect on the activity of genes in only certain parts of the brain or in the genitals in an adult?

Still, some fascinating work points to the possibility that epigenetic changes can be inherited. Several groups have found that rodents exposed to chronic stress produce offspring that are particularly sensitive to stress. For example, Isabel Mansoy of the University of Zurich and her colleagues separated mouse pups from their mothers in the first two weeks of their lives, and found that the male offspring showed signs of depression in adulthood. When these males were mated with normal females, the offspring showed similar depressive behavioral characteristics in adulthood, even though they were not exposed to stress in their early life. This transfer of susceptibility to stress is consistent with changes in the methylation levels of several unique genes in both sperm cells and the brain.

We conducted a similar study in our laboratory. According to our model of social defeat, we exposed male mice to chronic stress. We waited a month, then let these males breed. We found that their offspring showed a marked increase in the tendency to depression. We took the experiment one step further. If the epigenetic changes that make the mice prone to depression are indeed allowed, the changes should reach the gametes of the animal. We therefore took a sperm cell from our defeated males and used it to fertilize an egg cell from a normal female. The offspring from this artificial union, we found, were almost completely normal: they showed only slight signs of the withdrawn and anxious behavior that characterized their ancestors.

This experiment is not conclusive, because it is possible that epigenetic marks are somehow erased from the sperm during the in vitro fertilization process. But the results show that the females that mated physically with frightened males treated their pups differently than females that mated with normal males - or who never met the father of their pups. Hence, the depression in the offspring may have resulted from early behavioral experience and not from direct epigenetic inheritance through sperm or egg cells.

This does not mean that such transmission from generation to generation is not possible. However, we currently do not have absolute evidence for this. To try to answer the question, we need to develop experimental tools that will allow us to identify the relevant epigenetic changes in germ cells and show that these changes are both necessary and sufficient to bring about the observed transfer of traits.

The 18th century biologist Jean-Baptiste Lamarck became famous for his theory of the inheritance of acquired traits. According to him, traits that living things develop during their lives, developed muscles, for example, can be passed on to their offspring. Today we know, of course, that genes play a central role in determining physiology and function. But, scientists are beginning to understand more and more how much exposure to the environment and different experiences (including random occurrences) during development and adult life can change the activity of our genes, and hence the modes of expression of these traits. And we now know that epigenetic mechanisms mediate this interplay between heredity and environment. Much work remains to be done to understand how and to what extent epigenetics affects behavioral traits and susceptibility to mental illness, and if such sensitivities are passed on to future generations. Mark and his critics were certainly willing to debate the possibilities.

About the author

Eric G. Nestler is a professor of neuroscience, trustee of the Nash Family Chair and director of the Friedman Brain Institute at Mount Sinai Medical Center in New York City. His laboratory is engaged in the study of the molecular mechanisms leading to drug addiction and depression.

More on the subject

Epigenetic Regulation in Psychiatric Disorders. N. Tsankova, W. Renthal, A. Kumar and Eric J. Nestler in Nature Reviews Neuroscience, Vol. 8, pages 355-367; May 2007.

Epigenetic Programming of Phenotypic Variations in Reproductive Strategies in the Rat through Maternal Care. NM Cameron et al. in Journal of Neuroendocrinology, Vol. 20, no. 6, pages 795-801; June 2008.

Why DNA Isn't Your Destiny. John Cloud in Time, Vol. 175, no. 2; January 18, 2010.,9171,1952313,00.html

Epigenetic Regulation of Genes in Learning and Memory. TL Roth, ED Roth and JD Sweatt in Essays in Biochemistry, Vol. 48, no. 1, pages 263-274; September 2010.

Epigenetic Transmission of the Impact of Early Stress across Generations. TB Franklin et al. in Biological Psychiatry, Vol. 68, no. 5, pages 408-415; September 1, 2010.

The Epigenetic Landscape of Addiction. I. Maze and Eric J. Nestler in Annals of the New York Academy of Sciences, Vol. 1216, pages 99-113; January 2011.

Epigenetics at the University of Utah's Learn.Genetics site:

21 תגובות

  1. Every end is a new beginning.
    You learn a lot from stories about childhood stories. Sounds like you're dreading the day your adventures run out...
    Not sure that you "doubted like me". My doubts and your doubts do not necessarily come from the same source. My problem is not with the phenomena, because there is no point in arguing with facts, but with the accepted explanations.
    The method of tapping from one system to another is not new. It is as old as human thinking, and maybe even more so. Individual successes encourage to continue, but the scientific test is precisely in the failures.

  2. I have already uploaded all the data for solving the puzzle before. I think the issue has been summed up.

    I finished watching the lectures on relativity, but they didn't update me much. I am now trying to find time for lectures on cosmology. Unfortunately, it doesn't seem to me that Susskind himself answers questions on his blog anymore as he used to do in the past. Either way, it's a great way to learn. At the time, when I, like you, doubted the truths of non-locality in quantum entanglement, I devoted time and effort to his lectures, but as soon as I was convinced of the correctness of the claim, the matter immediately ceased and I did not finish the entire series of lectures. If I hadn't been convinced, I would have continued to the end and learned a lot along the way.

    It reminds me of a great story I read when I was a child: a boy in a kibbutz lost his bicycle and goes out with his father to look for it. On the way they go through different adventures and when they finally find them, the boy bursts into tears because the adventures are over.

    That's why I don't have a problem if I don't immediately find the answers to the questions I'm asking. I learn a lot along the way, and it is much more interesting to learn this way than school or university.

    Just a few last words about psychomechanics and time dilation: As I have already mentioned before, I am now working on planning an experiment to see if there is any truth to the subject of absolute time and the inconstancy of the speed of light.

    If I had the choice between the success of this experiment and the success of the experiment in psychotechnology - which, as mentioned, has already succeeded, and all that remains is to check its record over time and its long-term effects on the environment (and hence psychomechanics) - I would without hesitation choose psychotechnology.

    Ruth end.

  3. Israel, you are cute.
    Will you give me time to think of a solution? Say, a thousand years back?
    Until then, maybe tell me what brings you to this riddle?
    And regardless (apologies for deviating from the topic), have you finished watching Susskind's lectures?

  4. jubilee

    If you were short-sighted 1000 years ago, what would you prefer:

    1. Glasses that will correct your vision and allow you to function normally.

    2. Credit for the invention of the glasses includes all honors, but without the glasses themselves.

    You can only choose one of the two.

  5. One hundred percent Israel, go for it. You got a green light from me (as if you needed it).
    If you ask, I will always give you a critique - and I have plenty of that.
    And when the day comes, when your name will hit tsunami waves and make noise in the bows of the cypresses, I will be able to proudly say that I was your chileba.

  6. jubilee

    "The concept of "happiness" can be defined quantitatively based on the degree of oppression"

    Not according to my words. According to my words, we currently do not have a definition for happiness, although we know very well what it is even without a definition. (Same as above regarding blue color, sour taste, and beautiful song).

    "Assuming that by the word entropy you meant heat" No, I didn't mean it. Entropy is not heat, although it can be quantified as the amount of heat differences in a thermodynamic system divided by the absolute temperature. Because of the similarity between thermodynamic entropy and the amount of disorder in systems in general, it is customary to use the concept of entropy as a measure of general disorder, and this is also its use in psychomechanics.

    "You compare a certain emotion, anger in your example, to entropy" Anger does pass from person to person, and so can entropy pass from system to system. I try to take systems whose laws are already known to us, tap into systems that behave in a similar way, and derive the laws of the new systems, in our case psychological systems. This is an accepted method in physics, by sine waves.

    In conclusion, thermodynamics is quite a complex science, although not quite as complicated and unintuitive as quantum for example. It was founded mainly to take care of existing systems, steam engines for example, which were built by inventors with almost no knowledge of thermodynamics (as the Wright brothers had only a little knowledge of aerodynamics, but nevertheless managed to build an airplane before all the giant corporations of their time).

    Psychomechanics also tries to give the theoretical framework to an existing technology, psychotechnology. In comparison, the glasses already exist, the science of optics does not yet.

    And thus it seems to me that we can end the discussion of psychomechanics.

  7. If I understood your words correctly, the concept of "happiness" can be defined quantitatively based on the degree of stress that led to depression, and this is measured by observations of the epigenetic changes which can be performed using tools accepted in biological laboratories. That is, happiness and depression are different numbers on some common axis. After the discussions in that philosophy course, in which we chewed on this exact definition until we decided to throw it up in the face of much more complex definitions (which we also threw up), I can no longer accept it.
    You compare a certain emotion, anger in your example, to entropy and say that according to the second law of thermodynamics the "aspiration" of any system is to lower the level of entropy in which it is charged by the fact that it "chooses" for itself the easiest goal to transfer the excess charge to. I went to Wikipedia and got the following three alternative definitions for the second law of thermodynamics:
    * It is not possible to build a heat machine, which utilizes the heat of a single heat reservoir (Heat Reservoir), and turns it into work (formulation of the second law according to Lord Kelvin).
    * Spontaneous flow of heat will always occur from a hotter body to a colder body, and never the other way around. (The wording of the law according to Clausius).
    * The amount of entropy in a closed system is never small and can only increase.
    I did not find a clear connection between your definitions and what Wiki says. The first two definitions do not talk about entropy but about heat. The third definition does talk about entropy, but it does not relate to the transfer of this entity from system to system. As far as I know, a physical body does not have a voluntary tendency to lower its own heat level (that is, assuming that by the word entropy you meant heat) but heat has a tendency to dissipate. Also, the cooling body does not choose to whom to transfer the excess heat, but all the bodies in the environment absorb the heat according to their specific tendencies. Anti-Semitism is hatred focused on one specific system, therefore it is impossible to define anti-Semitism according to thermodynamics.
    For these reasons I find that the comparison you make is not good.
    I do believe that there is a cause for anti-Semitism, but it is not the natural feeling of hatred that nests in every person. Hatred and rage are only one of the ways in which anti-Semitism is expressed, but its roots are very deep.

  8. jubilee.
    Who is hiding? Look at the dates, they are from two days ago.

    What's wrong with IQ100? Why is the starting point that we have to be above average, doesn't that require someone else to be below? What's more, IQ is in its rightful place, but it is only part of the overall picture, and is such a common measure, perhaps because it can be measured. According to many serious researchers, there are many types of intelligence (humor, movement, drawing, writing, and above all emotional intelligence), which are extremely difficult to quantify, but are just as important as IQ.

    The concept of "happiness" is one of those concepts that are very difficult to define, even though we know very well what they are. (See "arete" or "quality" in Pirsig's "Zen and Art of Motorcycle Maintenance"). In the article above, the mice became depressed to the point of genetic change as a result of social stress. Do you think this would have happened if they were "happy" even though we didn't define what happiness is? So here is the empiricism you asked for. A laboratory experiment in mice, from which it is possible (as the experimenters claim) to tap into human friendships.

    But what is the reason for that strain of the mice in question? From the article: "We work with mice that are exposed to constant social defeat". Note: they do not lack food or security. The reason for the depression of those mice is only other mice.

    If the happy group of Poe and his friends in the Ashdon Forest had been exposed to other, more dominant and errant characters, with whom they could not cope, I assume (true, without proof) that their lives would have been less happy, much less, and this despite the fact that those characters do not pose a physical danger to the original characters.

    This is also the reason, in my opinion, for the seclusion of many of the human societies and their isolation from the majority in a kind of "private paradise of fools" which is still a paradise, because there is no need to deal with the more successful elements.

    And here is the place of psychomechanics, and the second law of psychodynamics.

    Without going into confusing details, take a certain emotion, anger. He goes from one to another: the boss yells at his deputy (thereby reducing his personal anger) the deputy yells at the secretary, who yells at the children, who beat the neighbor's kids, who beat the cat. The sergeant grabs a pair of bicycles with his finger, and hits a protester with a rifle, who will shout at the soldier, beat the other demonstrators, who will throw stones... Had Gadiya, Had Gadiya.

    Each one lowers his entropy so as to raise that of the other.

    And whose entropy is the easiest to raise? of the weak and lacking the ability to defend themselves of course.

    Here come the Slavs and say: hit the Jews and save Russia. The Aryans say: let's get rid of the subjugation of the Jewish man (Aryans... have you seen Hitler, Goebbels, Bormann, Himmler and most of the Nazi leadership? They look like Jews from the shtetl).

    When the German soldiers entered Russia, they were told that the Russians were subhuman. After the battle for Moscow, they changed their minds and started calling the Russian soldiers Supreme Man. I pretty much believe that this is what would have happened to the Wafan SS units if they encountered Shladg or 890 units.

    Because it seems to me that your claim implies that there may be a real reason for anti-Semitism, that if the Swedish Jews were tall, blonde, blue-eyed, there would be no anti-Semitism (who can hate beautiful Nordic girls?).

    This is a weighty claim, but it seems to me that we have stopped for now, what's more, I am not sure that this is indeed your claim.

  9. Israel!
    Somehow I can't shake the feeling that the comment about IQ100 is aimed directly at him. Maybe because the hat is on fire on the thief's head, or maybe it's just paranoia.
    The first written work I was asked to submit in the philosophy course I took four years ago was the definition of the concept of "happiness". We were a class of twenty-five old men and women, including the professor, and we came to the conclusion together that this definition is elusive and far from quantifiable. If I had your definition, I might be tempted to use it and create a revolution in human thinking. And if I had a shred of conscience, maybe I would give a credit card to some Israeli who left the country. Naaa!! Am I a conscientious objector?! in dreams

  10. my father

    A group of hair shavers is on the rampage in Kiev. One of the beaten protests: Hey, why are you beating me, I'm anti-Semitic at all!

    "We don't care what kind of name you are," the hooligans reply, "My name is my name!"

    Yuval - after Apota. Meanwhile from the article:

    "This is the essence of the second law of psychomechanics. Order in the thermodynamic system is compared to happiness in the psychodynamic system, and just as the tendency of order in a closed thermodynamic system is to decrease with time, so the tendency of happiness in a closed psychomechanical system, such as the earth, is to decrease, which causes the system to spread and push the dissatisfaction to the social margins that are left behind.
    If you succeeded through hard work and study to improve your score on the psychometric exam or the QI test, you inevitably pushed someone else down, because I Q100 by its very definition is a measure that reflects average intelligence.

    And the same will happen to you if you are forced to compete for your place at the university with a group of endlessly diligent and talented Kashidim Chinese, who will raise the bar of grades and fix you without a way out on the left side of the bell curve."

  11. Recently, NASA managed to photograph a galaxy made of antimatter, or in short an antigalaxy. Inside the anti-galaxy there is an anti-solar system and inside it an anti-Earth. In the building in the anti-Earth, next to the anti-Shulchan sits an anti-Semite. The author of this grave joke deliberately tells it only in Hebrew.

  12. Before I answer I will refer to your clarification. Please feel free to answer it. From what you said ("According to the argument of psychomechanics, it does not matter at all what the Jews will do, who they are, what they are and whether they even exist. The source of the problem is one group - the anti-Semites - which tries to lower its own psychomechanical entropy by increasing the entropy of another group, the Jews") It is implied that for the anti-Semitic group it doesn't matter who to take care of, as long as some anguish (which you call "entropy") is removed from them. But from my understanding of world history and the face of things, this final hatred embraces the world without a unique group affiliation and is directed only towards Jews. On the face of it, the conclusion that anti-Semitism is unique to one human group (reminiscent of the Protocols of the Elders of Zion, in reverse) seems far-fetched without sufficient substantiation, and if psychomechanics claims this and ignores the facts on the ground instead of providing them with a plausible explanation, then something is flawed in it. It is possible that this is only a single case that should not disqualify an entire theory and then the term "flower sparrow" is out of place.

    Unfortunately, in all honesty, I can't answer the first two questions because I've never watched the corresponding TV series and I don't know the characters who act (I don't share the reason why I don't have a TV with well-known people. I just think that exposure to external stimuli weakens creativity) .
    To your third question: If I accept the postulates of psychomechanics, then your thesis will be self-evident. Twenty years ago I wrote a story describing a reality in which the human male population is extinct (as a result of the use of some biological weapon). All male jobs are taken by women (including the leadership of the Catholic Church, for example) and they come to the conclusion that the reality dictated by men has lost its relevance. Since the men are seen as "Mars" and the women as "Venus", I had to adapt my writing to the conventions, and in a short time all the wars in the world end. However, it is not easy to bend me, and over the course of a few decades a need for leadership develops and part of the population develops domineering tendencies, which creates social classes that correspond to the gender differences that exist in reality. As mentioned, your thesis (as well as mine) needs to adapt its axioms to the reality on which it is defined. "The implication if the theory is verified" is beautiful and interesting, but it is not necessarily the only possible one. And in any case, since I am honestly also an empiricist, I would not be complete with my conscience if I did not point out that this is an unborn egg.

  13. Thank you Yuval. To avoid misunderstandings, you should always read the sentence to the end, and if something is unclear, ask for clarification.

    1. I did not write "it is not clear if the Jewish people exists".

    I wrote: "According to the argument of psychomechanics, it does not matter at all what the Jews will do, who they are, what they are and whether they even exist. The source of the problem is one group - the anti-Semites - which tries to lower its own psychomechanical entropy by raising the entropy of another group, the Jews."

    And I also added: "According to the fundamental law of psychomechanics, our feelings arise from the form in which we perceive reality, even if it is only a simulated reality."

    It is quite clear, I believe, that I did not mean to deny the existence of the Jewish people.

    2. I asked: "Who are the people appearing in the picture that usually appears next to your name?"

    "Usually" by its very nature refers to the majority. If you look, you will see that usually the ones that appear are Pooh and Piglet.

    To the point:

    Pooh, Piglet, Kanga, Namur, Fig, Owl and the rest of their friends live peacefully and comfortably with Christopher Robin in the fantasyland that Milan created for them. For them, this is reality, everyone is friends, life flows smoothly and calmly and is full of exciting adventures. When the group thinks that Iyor is upset, everyone gathers to encourage and comfort him.

    In the following questions I am asking for your private opinion only. No need to back up with credentials.

    Question 1.

    If we refer to the article above, would it be normal for any of the heroes we mentioned to develop chronic depression and start using hard drugs with no way out?

    (You mentioned Piglet, but the original Piglet has a good friend, Pooh, and it is assumed that living in Ashdon Forest he would not have reached depression and addiction).

    Question 2.

    If we were to introduce heroes from other stories into the Winnie the Pooh story, Shirkan, Scar, Gafar, or even positive but jealous characters, Belle, Jasmine, Esmeralda, would that increase or decrease the chances of addiction for any of the original Winnie the Pooh characters (especially a piglet)?

    Question 3.

    In the past I referred to the subject of addiction that appears above in

    Here is a quote from her:

    "An interesting thesis being researched by the group refers to communities of addicts. The assumption is that under constant conditions, a certain and approximately constant percentage of the population will develop an addiction - to alcohol, drugs, food, gambling, etc. Addiction will focus on some people, and ignore others. Now, what will happen if we remove from the system to a lonely island all the drug addicts for example, and leave all the other conditions in the system as they were? According to the data of the original assumption, since the percentage of addicts is more or less constant, after the system reaches a new equilibrium, new addicts will spontaneously form to fill the ranks, while on the deserted island there will be a mass spontaneous withdrawal among the original addicts.
    Although there is insufficient experimental data to substantiate the thesis, the implication, if the theory is confirmed, is that the initial addicts, by their very existence, prevented the latter from becoming addicted, and this without them knowing them or even knowing their role in the system!"

    (Full disclosure: I have no tendency to addiction).

    Do you find any truth in the quote I brought from my article?

  14. Israel, fine. I still feel obligated to you from that time, so I'll flow with you, but first a note:
    I did not rule out "a sparrow is a flower" but only brought up this possibility as derived from the claim that "it is not clear if the Jewish people exists". This was my way (somewhat mass, I admit) to try to provoke you to correct, if you think it is necessary, and to expand and elaborate.
    My current photo was taken in February three years ago. Sometimes I write from other computers (I have five computers at home and sometimes I also write from computers at the university) and on them there are other pictures. One of them is taken from the movie Mowgli (at your request) and shows Mowgli with Baloo the Bear. And the second, more frequent, shows Winnie the Pooh and Piglet. Pooh and Baloo are "good-tempered mice" and Mowgli "aggressive". I do not attribute any of these qualities to the piglet. He is small, vulnerable and fragile and therefore will develop depressions. I identify with him.

  15. jubilee.

    My first question is:

    Who are the people in the picture that usually appears next to your name?


    From the quotes in the article above (under "marked for depression"), which qualities do you think are more suitable for the heroes of your picture:

    1. "Good-tempered mice"

    2. "More aggressive."

    The third question is: If we proceed from the assumption that the results of the laboratory experiment on mice described in the article are applicable to everyone (the assumption in the article, by the way, is that they are applicable to humans), do you think that the heroes of your picture would also become depressed like the mice in the article if they were placed in the same conditions?

  16. How does the reader know where the gene that needs to produce protein (can we say "to milk" in short?)
    Is there a different type of enzyme for each gene?

  17. If I were tested after and while reading this article
    It was determined that I was under the influence of pleasure and pleasure drugs.

  18. Fascinating, and this is a whole layer of information that is often ignored, despite its importance.

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