You can train yourself to deceive the body as if it received medicine.
Marette Flies was 11 years old when her immune system rebelled against her. In 1983, the girl found lupus. Systemic lupus erythematosus is an autoimmune disease in which antibodies damage the DNA of healthy cells. Marett's face was swollen from immunosuppressive drugs, and her hair fell out. Later, the kidneys began to inflame, convulsions appeared and blood pressure rose.
In 1985, antibodies attacked coagulation factors in the blood. Mariett removed the uterus - the girl could bleed out during menstruation. Despite the multitude of drugs, blood pressure increased. Heart problems appeared and the doctors decided to use Cytoxan, an extremely toxic medicine that could kill the girl.
But the human body is able to learn the conditioned reflex not only to the production of gastric juice, as it was in Pavlov's dog, but also to the suppression of immunity. The girl was rescued with fish oil and pink perfumes.
')
© Aaron Tilley and Kerry Hughes
Cytoxan (Cytoxan, active ingredient - Cyclophosphamide) perfectly suppresses the immune system. But among its side effects, in addition to nausea, cystitis and urethritis, disorders of the kidneys, the formation of cancerous tumors and a number of unpleasant and life-threatening things are described. At that time, its use in humans was experimental. Psychologist and pediatrician Karen Olness, who worked with Mariet, was sure: if the girl copes with stress and pain, then this drug will definitely kill her. And then mother Marett showed the doctors one study in which half of the usual dose of Cytoxan slowed the development of lupus in mice.
What's the secret? In that it is possible to train the body to respond to a medicine, so that in the future it will include the same triggers without a drug. Proponents of this phenomenon hope to reduce doses of drugs for the treatment of various diseases, including autoimmune and cancer, in order to minimize side effects and reduce costs.
Have you ever had a poisoning after a meal that you love so much? After such a case, you may not touch this dish for several weeks or months. This is called the "conditioned aversion reflex." In the past, this property helped people to survive - they did not try again food, from which they feel bad.
In 1975, a psychologist from New York studied the conditioned reflex of disgust in rats. Robert Ader of the University of Rochester gave the animals water with sugar . Rats love sweets, but for this experiment, Eider combined the drinking process with cytoxan injections. Then the scientist again gave the rats sweetened water, but they refused it. Therefore, Eider forced the animals with a dropper, after which they died.
Although cytoxan is toxic, rats did not receive a lethal dose. Animals not only learned that they feel bad after sweet water: their bodies remembered the response of the immune system. The response of immunity to sweetened water turned out to be the same as for the real medicine.
The phenomenon in which a signal leads to a physiological response was already known. It is called the "conditioned reflex", it was discovered in the 1890s by the Russian physiologist Ivan Pavlov. It was he who divided the entire set of reflexes into conditioned and unconditioned. In 1904, for his work in the physiology of digestion, Pavlov received the Nobel Prize in medicine and physiology.
Different signals affect the human body every day. They prepare us for food or sex, triggering physiological responses. Sometimes a person, just knowing that a cat is in the house, starts sneezing - even if there was no direct exposure to the allergen. Eider's experiment showed that the conditioned reflex works with the immune system, and that he can kill. The body's fight against disease is controlled in the same way by the brain as the production of gastric juice.
A similar discovery was made again in Russia, in the 1920s. Researchers at St. Petersburg State University continued Pavlov’s work to find out what other physiological responses could be trained. Among these researchers was Sergey Metalnikov , a zoologist and immunologist. Unlike Aider, he calved to strengthen the immune system, not suppress. So he transferred the teachings of Pavlov to immunology.
Metalnikov injected the bacteria into guinea pigs, while simultaneously heating their skin. Then he gave these pigs a lethal dose of Vibrio cholerae. Pigs that did not heat their skin after the injections — that is, they did not give the signal they studied — died after 8 hours. Others lived an average of 36 hours or were completely cured.
In the West, Russian teachings were forgotten, and Eider’s work was ignored. This is because no mechanism has been found by which an animal can memorize the response of the immune system. The immune and nervous systems were considered completely independent of each other, and Eider's theory that they are related seemed to be nonsense. Scientists were confident that the immune system responds to physical signals — infection and trauma — without any help from the brain.
Physiologist from Germany Manfred Schedlovski (Manfred Schedlowski) drew attention to the experiments with reflexes and wanted to use the described phenomenon to help people. He tried to work with various immunologists, but they, as a rule, did not even listen to him. One of the scientists interrupted him in the second minute: “Dr. Schedlovski, if you want to do something like this, become an artist. There is nothing to do with science. ”
The scientist began his own experiments on rats - with saccharin and CsA preparation, which has an effect of immunosuppression similar to Cytoxan. Schedlowski found that the response to saccharin without the drug suppresses the proliferation of white blood cells in the blood and reduces the production of two vital elements of the immune system - the cytokines IL-2 and IFN-Îł, just like a drug.
Shchedlovsky continued the search for areas where such a conditioned reflex can be used in medicine. He was already thinking that it would help people after transplantation, when the recipient's immune system attacks an alien organ. To test his assumption, Shchedlovsky transplanted second hearts into the abdominal cavity of rats, gave the animals sweetened water with ScA, and then removed the drug and gave only water with saccharin. These rats carried extra hearts for an average of 3 days longer than the control group, and as long as the rats that received the real drug.
The following experiment was more interesting. A group of rats that received small doses of CsA, lived an average of 8 days after transplantation. The full course of the drug extended the lives of other rats to 11 days. But those rats in which a reflex was developed, and with which small doses of CsA were added, were able to wear excess hearts for an average of 28 days, and more than 20% of this group then lived for several months.
Schedlowski feared that the learned associations would weaken over time, and the conditioned reflex of the immune system would not help patients for long-term treatment. But if you combine this reflex with low doses of the drug, you can extend the effect.
A few years after the publication of Aider, scientist David Felten from the Medical School of the Indiana University realized that he was criticized in Aider’s work: there was no evidence of a connection between the immune and nervous systems. Using a powerful microscope, Felten began to track the nerve endings in the exposed mice. He found that the nerves are connected not only with blood vessels, but also with the organs responsible for immunity - with the spleen and thymus gland. After that, Felten moved to the University of Rochester to work with Aider and his colleague Nicholas Cohen. All three became pioneers in the field of medicine known as psychoneuroimmunology - it is based on the idea of ​​the brain and the immune system working together to protect people from disease.
Eider tried to understand how this knowledge would help patients. The conditioned reflex can kill mice, but can it cure diseases, as is the case with the Russian scientist Metalnikov and his guinea pigs? And then Eider was called - a 13-year-old girl was desperate for his help.
In 1982, Eider again used the production of conditioned reflexes to treat mice with an autoimmune disease like lupus. He coached them to associate cytoxan with a saccharin solution, as in the original experiment. After creating the association, he continued to give the mice sweetened water and half the usual dose of the drug. The disease in these mice developed more slowly than in those who simply received half the dose. It was this study that Marett's mother brought to the doctors.
Karen Olness phoned Eider and asked if this method could work on Mariet. Is it possible to train the immune system to respond to low doses of the drug in order to save the girl from strong side effects? Eider agreed.
Doctors have teamed up to develop ways to treat Marett. The first question was the choice of signals. They must be unique and memorable. There were suggestions to drink vinegar or liqueurs, there are eucalyptus chips. In the end, they chose a combination of fish oil with perfume with a rose scent.
The emergency hospital approved this treatment, and the next morning, the doctors began the experiment. The girl drank fish oil in sips while Cytoxan was injected into her body through a vein in her leg. At the same time, the pediatrician sprayed perfume around the room.
This ritual was repeated once a month for the next three months. After that, every month Marette continued to drink fish oil and breathe perfume, but received doses of the drug every three months. By the end of the year, instead of twelve doses of the drug, the girl received six. And her body reacted to them as well as the full course . The coagulability factor of blood returned, the pressure returned to normal. After 15 months, the girl stopped drinking fat and breathing the rose, but continued to imagine the smell of the rose, which she believed helped her calm the immune system. The girl graduated from school and went to college.
At nine o'clock in the morning and in the evening, 46-year-old Barbara Novak sets an alarm clock at a kitchen table in her home in Sprokhovel, in the northern part of Germany, and drinks a powerful cocktail of immunosuppressive drugs. This is Tacrolimus, Mowel and Prednisone. But before that, the woman forces herself to drink a strange drink - sweet, bitter, neon green and with a strong taste of lavender.
In 1988, when Novak was 19 years old, she was preparing for exams. And at that moment, she lost both of her kidneys because of lupus. She spent many years on dialysis, sitting 12 hours a week in a local clinic with a large needle in her hand - she still has scars. A kidney from a donor has changed her life. She had the strength to travel around Europe, to participate in geocaching competitions (search for caches by GPS-coordinates) with her dog. But there was also the other side of the medal - twice a day she needed to take drugs to suppress the immune system so that her body did not destroy the new organ. And the side effects of these drugs poisoned her along with the kidney. One of them later began to destroy the red blood cells.
The woman decided to take part in the experiment of the University of Essen, where he worked Shchedlovski. The famous green drink, as Schedlowski’s students called it, is the new version of the rose and fish oil combination that Mariet used. Like Eider, Shchedlovsky wanted to find something memorable and unique, and at the same time stimulated several senses at a time. He took strawberry milk, dyed it with the help of food coloring in green color and added essential oil. This drink was tested on a group of healthy volunteers. The effect of the drug CsA, he replaced by 60-80%.
Novak, along with several other patients in 2013, was scheduled to take her drugs, placebo and a green drink. This is her third transplanted kidney. The first lasted a week, the second - 13 years and refused due to the effects of drugs. She hopes that the third will help her live much longer.
There are many ways to use reflexes, in addition to suppressing immunity after transplantation. This discovery may weaken the side effects and make the treatment more accessible.
In 1996, Eider gave ten patients with multiple sclerosis, an autoimmune disease, a flavored anise syrup paired with cytoxan. Later, he began to give them a placebo syrup, and eight out of ten responded to the placebo with immunosuppression in the same way as with cytoxan. Shortly before his death in 2011, Eider published a study where a quarter or half of a dose of an ointment with corticosteroids after a reflex produced helped to treat psoriasis, as with a full dosage.
In 2010, as part of the experiment, a method of reducing the dose of a drug controlled by placebo was applied. Children with attention deficit hyperactivity disorder (ADHD) were given white-green pills (placebo) along with regular medications. At the same time, the children knew that they were drinking placebo. Later, the dose was reduced, leaving the white-green pills. Children in the half-dose group with placebo had better results than children who just received half the dose. If this method is used in the US, you can save huge amounts of money to the budget - only drugs for ADHD take 5.3 billion dollars a year.
Reducing drug costs is good for people who need treatment, and for the state as a whole. But pharmaceutical companies will by all means discourage this - or they will have to double the price of drugs to keep profits.
Pediatrician Adrian Sandler from Sevena Carolina, who conducted the experiment in 2010, would like to continue his experiments in helping children with ADHD and other diseases like autism. But his applications for funding are rejected.
Ivan Pavlov received the Nobel Prize when he showed that the digestive system is controlled by the brain - until that moment it was believed that it was independent. Despite the fact that Eider and Felten proved that the same principle is valid in immunology, they are little known. Schedlowski, supported by the German Research Foundation DFG, heads one of the few teams working with conditioned reflexes of the immune system: “I like to say that we are the best in the world. Because there is nobody else! ”
Sources:
Can the Immune System Be Taught? (Episode from the movie The Mind Body Connection)
You had
Behaviorally conditioned immunosuppression
Conditioning as an adjunct in pharmacotherapy of lupus erythematosus.
Conditioned Placebo Dose Reduction: A new treatment in ADHD?
Correspondence N.K. Roerich and S.I. Metalnikov
In 1985, antibodies attacked coagulation factors in the blood. Mariett removed the uterus - the girl could bleed out during menstruation. Despite the multitude of drugs, blood pressure increased. Heart problems appeared and the doctors decided to use Cytoxan, an extremely toxic medicine that could kill the girl.
But the human body is able to learn the conditioned reflex not only to the production of gastric juice, as it was in Pavlov's dog, but also to the suppression of immunity. The girl was rescued with fish oil and pink perfumes.
')
© Aaron Tilley and Kerry Hughes
Cytoxan (Cytoxan, active ingredient - Cyclophosphamide) perfectly suppresses the immune system. But among its side effects, in addition to nausea, cystitis and urethritis, disorders of the kidneys, the formation of cancerous tumors and a number of unpleasant and life-threatening things are described. At that time, its use in humans was experimental. Psychologist and pediatrician Karen Olness, who worked with Mariet, was sure: if the girl copes with stress and pain, then this drug will definitely kill her. And then mother Marett showed the doctors one study in which half of the usual dose of Cytoxan slowed the development of lupus in mice.
What's the secret? In that it is possible to train the body to respond to a medicine, so that in the future it will include the same triggers without a drug. Proponents of this phenomenon hope to reduce doses of drugs for the treatment of various diseases, including autoimmune and cancer, in order to minimize side effects and reduce costs.
Pavlov's Dog, Metalnikov's Guinea Pigs and Eider Mouse
Have you ever had a poisoning after a meal that you love so much? After such a case, you may not touch this dish for several weeks or months. This is called the "conditioned aversion reflex." In the past, this property helped people to survive - they did not try again food, from which they feel bad.
In 1975, a psychologist from New York studied the conditioned reflex of disgust in rats. Robert Ader of the University of Rochester gave the animals water with sugar . Rats love sweets, but for this experiment, Eider combined the drinking process with cytoxan injections. Then the scientist again gave the rats sweetened water, but they refused it. Therefore, Eider forced the animals with a dropper, after which they died.
Although cytoxan is toxic, rats did not receive a lethal dose. Animals not only learned that they feel bad after sweet water: their bodies remembered the response of the immune system. The response of immunity to sweetened water turned out to be the same as for the real medicine.
The phenomenon in which a signal leads to a physiological response was already known. It is called the "conditioned reflex", it was discovered in the 1890s by the Russian physiologist Ivan Pavlov. It was he who divided the entire set of reflexes into conditioned and unconditioned. In 1904, for his work in the physiology of digestion, Pavlov received the Nobel Prize in medicine and physiology.
Different signals affect the human body every day. They prepare us for food or sex, triggering physiological responses. Sometimes a person, just knowing that a cat is in the house, starts sneezing - even if there was no direct exposure to the allergen. Eider's experiment showed that the conditioned reflex works with the immune system, and that he can kill. The body's fight against disease is controlled in the same way by the brain as the production of gastric juice.
A similar discovery was made again in Russia, in the 1920s. Researchers at St. Petersburg State University continued Pavlov’s work to find out what other physiological responses could be trained. Among these researchers was Sergey Metalnikov , a zoologist and immunologist. Unlike Aider, he calved to strengthen the immune system, not suppress. So he transferred the teachings of Pavlov to immunology.
Now I am working on the creation and justification of a new theory of immunity. Until now, physico-chemical theories of immunity predominated mainly in medicine and physiology. Immunity has been studied as an autonomous process, which proceeds in the main [th] image [s] in the blood. I argue on the basis of a number of experiments on various animals that the main role in immunity is played by the nervous system and mental factors. I don’t remember if I sent you my latest article “Factoures biologique et psychique de l'immunite” [17]. I am preparing now a book about the "Role of the nervous system and mental factors in immunity." That is why I am now interested in Yoga. The books you sent did not quite satisfy me. Still, it is not clear to me how the will is brought up over one’s own body to such an extent that a person is able to arbitrarily stop the heartbeat or stop bleeding. I am surprised that in India, where there are Universities and laboratories, this has not yet been studied. It seems to me that one of the main tasks of modern science is to free our soul from slavish dependence [on] our body. The master should not be our body and various physiological processes, but my spiritual “I”. S. Metalnikov, from a letter to N. K. Roerich, April 16, 1932. A source
Metalnikov injected the bacteria into guinea pigs, while simultaneously heating their skin. Then he gave these pigs a lethal dose of Vibrio cholerae. Pigs that did not heat their skin after the injections — that is, they did not give the signal they studied — died after 8 hours. Others lived an average of 36 hours or were completely cured.
In the West, Russian teachings were forgotten, and Eider’s work was ignored. This is because no mechanism has been found by which an animal can memorize the response of the immune system. The immune and nervous systems were considered completely independent of each other, and Eider's theory that they are related seemed to be nonsense. Scientists were confident that the immune system responds to physical signals — infection and trauma — without any help from the brain.
Physiologist from Germany Manfred Schedlovski (Manfred Schedlowski) drew attention to the experiments with reflexes and wanted to use the described phenomenon to help people. He tried to work with various immunologists, but they, as a rule, did not even listen to him. One of the scientists interrupted him in the second minute: “Dr. Schedlovski, if you want to do something like this, become an artist. There is nothing to do with science. ”
The scientist began his own experiments on rats - with saccharin and CsA preparation, which has an effect of immunosuppression similar to Cytoxan. Schedlowski found that the response to saccharin without the drug suppresses the proliferation of white blood cells in the blood and reduces the production of two vital elements of the immune system - the cytokines IL-2 and IFN-Îł, just like a drug.
Shchedlovsky continued the search for areas where such a conditioned reflex can be used in medicine. He was already thinking that it would help people after transplantation, when the recipient's immune system attacks an alien organ. To test his assumption, Shchedlovsky transplanted second hearts into the abdominal cavity of rats, gave the animals sweetened water with ScA, and then removed the drug and gave only water with saccharin. These rats carried extra hearts for an average of 3 days longer than the control group, and as long as the rats that received the real drug.
The following experiment was more interesting. A group of rats that received small doses of CsA, lived an average of 8 days after transplantation. The full course of the drug extended the lives of other rats to 11 days. But those rats in which a reflex was developed, and with which small doses of CsA were added, were able to wear excess hearts for an average of 28 days, and more than 20% of this group then lived for several months.
Schedlowski feared that the learned associations would weaken over time, and the conditioned reflex of the immune system would not help patients for long-term treatment. But if you combine this reflex with low doses of the drug, you can extend the effect.
A few years after the publication of Aider, scientist David Felten from the Medical School of the Indiana University realized that he was criticized in Aider’s work: there was no evidence of a connection between the immune and nervous systems. Using a powerful microscope, Felten began to track the nerve endings in the exposed mice. He found that the nerves are connected not only with blood vessels, but also with the organs responsible for immunity - with the spleen and thymus gland. After that, Felten moved to the University of Rochester to work with Aider and his colleague Nicholas Cohen. All three became pioneers in the field of medicine known as psychoneuroimmunology - it is based on the idea of ​​the brain and the immune system working together to protect people from disease.
Eider tried to understand how this knowledge would help patients. The conditioned reflex can kill mice, but can it cure diseases, as is the case with the Russian scientist Metalnikov and his guinea pigs? And then Eider was called - a 13-year-old girl was desperate for his help.
Fish oil and rose smell
In 1982, Eider again used the production of conditioned reflexes to treat mice with an autoimmune disease like lupus. He coached them to associate cytoxan with a saccharin solution, as in the original experiment. After creating the association, he continued to give the mice sweetened water and half the usual dose of the drug. The disease in these mice developed more slowly than in those who simply received half the dose. It was this study that Marett's mother brought to the doctors.
Karen Olness phoned Eider and asked if this method could work on Mariet. Is it possible to train the immune system to respond to low doses of the drug in order to save the girl from strong side effects? Eider agreed.
Doctors have teamed up to develop ways to treat Marett. The first question was the choice of signals. They must be unique and memorable. There were suggestions to drink vinegar or liqueurs, there are eucalyptus chips. In the end, they chose a combination of fish oil with perfume with a rose scent.
The emergency hospital approved this treatment, and the next morning, the doctors began the experiment. The girl drank fish oil in sips while Cytoxan was injected into her body through a vein in her leg. At the same time, the pediatrician sprayed perfume around the room.
This ritual was repeated once a month for the next three months. After that, every month Marette continued to drink fish oil and breathe perfume, but received doses of the drug every three months. By the end of the year, instead of twelve doses of the drug, the girl received six. And her body reacted to them as well as the full course . The coagulability factor of blood returned, the pressure returned to normal. After 15 months, the girl stopped drinking fat and breathing the rose, but continued to imagine the smell of the rose, which she believed helped her calm the immune system. The girl graduated from school and went to college.
Green Strawberry Lavender Milk
At nine o'clock in the morning and in the evening, 46-year-old Barbara Novak sets an alarm clock at a kitchen table in her home in Sprokhovel, in the northern part of Germany, and drinks a powerful cocktail of immunosuppressive drugs. This is Tacrolimus, Mowel and Prednisone. But before that, the woman forces herself to drink a strange drink - sweet, bitter, neon green and with a strong taste of lavender.
In 1988, when Novak was 19 years old, she was preparing for exams. And at that moment, she lost both of her kidneys because of lupus. She spent many years on dialysis, sitting 12 hours a week in a local clinic with a large needle in her hand - she still has scars. A kidney from a donor has changed her life. She had the strength to travel around Europe, to participate in geocaching competitions (search for caches by GPS-coordinates) with her dog. But there was also the other side of the medal - twice a day she needed to take drugs to suppress the immune system so that her body did not destroy the new organ. And the side effects of these drugs poisoned her along with the kidney. One of them later began to destroy the red blood cells.
The woman decided to take part in the experiment of the University of Essen, where he worked Shchedlovski. The famous green drink, as Schedlowski’s students called it, is the new version of the rose and fish oil combination that Mariet used. Like Eider, Shchedlovsky wanted to find something memorable and unique, and at the same time stimulated several senses at a time. He took strawberry milk, dyed it with the help of food coloring in green color and added essential oil. This drink was tested on a group of healthy volunteers. The effect of the drug CsA, he replaced by 60-80%.
Novak, along with several other patients in 2013, was scheduled to take her drugs, placebo and a green drink. This is her third transplanted kidney. The first lasted a week, the second - 13 years and refused due to the effects of drugs. She hopes that the third will help her live much longer.
Children and Placebo
There are many ways to use reflexes, in addition to suppressing immunity after transplantation. This discovery may weaken the side effects and make the treatment more accessible.
In 1996, Eider gave ten patients with multiple sclerosis, an autoimmune disease, a flavored anise syrup paired with cytoxan. Later, he began to give them a placebo syrup, and eight out of ten responded to the placebo with immunosuppression in the same way as with cytoxan. Shortly before his death in 2011, Eider published a study where a quarter or half of a dose of an ointment with corticosteroids after a reflex produced helped to treat psoriasis, as with a full dosage.
In 2010, as part of the experiment, a method of reducing the dose of a drug controlled by placebo was applied. Children with attention deficit hyperactivity disorder (ADHD) were given white-green pills (placebo) along with regular medications. At the same time, the children knew that they were drinking placebo. Later, the dose was reduced, leaving the white-green pills. Children in the half-dose group with placebo had better results than children who just received half the dose. If this method is used in the US, you can save huge amounts of money to the budget - only drugs for ADHD take 5.3 billion dollars a year.
Who is against
Reducing drug costs is good for people who need treatment, and for the state as a whole. But pharmaceutical companies will by all means discourage this - or they will have to double the price of drugs to keep profits.
Pediatrician Adrian Sandler from Sevena Carolina, who conducted the experiment in 2010, would like to continue his experiments in helping children with ADHD and other diseases like autism. But his applications for funding are rejected.
Ivan Pavlov received the Nobel Prize when he showed that the digestive system is controlled by the brain - until that moment it was believed that it was independent. Despite the fact that Eider and Felten proved that the same principle is valid in immunology, they are little known. Schedlowski, supported by the German Research Foundation DFG, heads one of the few teams working with conditioned reflexes of the immune system: “I like to say that we are the best in the world. Because there is nobody else! ”
Sources:
Can the Immune System Be Taught? (Episode from the movie The Mind Body Connection)
You had
Behaviorally conditioned immunosuppression
Conditioning as an adjunct in pharmacotherapy of lupus erythematosus.
Conditioned Placebo Dose Reduction: A new treatment in ADHD?
Correspondence N.K. Roerich and S.I. Metalnikov
Source: https://habr.com/ru/post/390551/
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