You can train to deceive the body, as if it received a medicine
Marette Flies was 11 years old when her immune system rebelled against her. In 1983, a lupus was found in a girl. Systemic lupus erythematosus is an autoimmune disease in which antibodies damage the DNA of healthy cells. From immunosuppressive drugs, Marett's face was swollen, and her hair fell out. Later, kidneys became inflamed, cramps appeared and blood pressure rose.
In 1985, antibodies attacked coagulation factors in the blood. Marett removed the uterus - the girl could bleed during menstruation. Despite many drugs, blood pressure rose. 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 a conditioned reflex not only for the production of gastric juice, as was the case with Pavlov’s dog, but also for the suppression of immunity. The girl was saved with the help of 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, impaired renal function, 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. The psychologist and pediatrician Karen Olness, who worked with Marett, was sure: if the girl copes with stress and pain, then this drug will definitely kill her. And then Marett's mother 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? The fact that you can train the body to respond to the medicine so that in the future it will include the same triggers without the drug. Proponents of this phenomenon hope to reduce the dose of drugs to treat various diseases, including autoimmune and cancer, in order to minimize side effects and reduce the cost.
Have you ever had poisoning after a meal that you really love? After such an event, you may not be able to touch this dish for several weeks or months. This is called the "conditioned reflex of disgust." In the past, this property helped people survive - they did not try food again, which made them sick.
In 1975, a psychologist from New York studied the conditioned reflex of disgust in rats. Robert Ader of the University of Rochester gave animals water with sugar . Rats love sweets, but for this experiment, Aider combined the drinking process with injections of cytoxan. Then the scientist again gave the rats sweetened water, but they refused it. Therefore, Aider forcefully pipetted the animals, after which they died.
Although cytoxan is toxic, rats have not received a lethal dose. Animals not only learned that they feel bad after sweet water: their body remembered the response of the immune system. The immune response 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 has already been known. It is called the “conditioned reflex”; it was discovered by the Russian physiologist Ivan Pavlov in the 1890s. It was he who divided the totality of reflexes into conditioned and unconditioned. In 1904, Pavlov received the Nobel Prize in medicine and physiology for his work on the physiology of digestion.
Different signals affect the human body every day. They prepare us for food or sex, triggering physiological reactions. Sometimes a person, just knowing that there is a cat in the house, begins to sneeze - 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 it 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 might be trained. Among these researchers was Sergey Metalnikov, zoologist and immunologist. Unlike Eider, he calved to strengthen the immune system, not suppress. So he transferred the teachings of Pavlov to immunology.
Metalnikov injected bacteria into guinea pigs while warming their skin. He then gave these pigs a lethal dose of cholera vibrio. The pigs, which after the injections did not heat the skin - that is, 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, they forgot about Russian teachings, and Eider’s work was ignored. This is because no mechanism was found by which the animal can remember 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 connected seemed delusional. Scientists were convinced that the immune system responds to physical signals - to infection and injuries - without any help from the brain.
Physiologist from GermanyManfred Schedlowski drew attention to 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. Schedlowski, 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 a CsA drug, which has the effect of immunosuppression similar to Cytoxan. Shchedlovsky found that a response to saccharin without a drug inhibits the growth 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-γ, just like the drug.
Schedlowski continued to search for areas where such a conditioned reflex can be used in medicine. He already thought that this would help people after transplantation, when the recipient's immune system attacks an alien organ. To test his assumption, Schedlowski transplanted second hearts into the abdominal cavity of rats, gave animals sweetened water with ScA, and then removed the drug and gave only water with saccharin. These rats transferred 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 next experiment turned out to be more interesting. The group of rats that received small doses of CsA lived on average 8 days after transplantation. A full course of the drug extended the life of other rats to 11 days. But those rats that developed a reflex and were given small doses of CsA were able to carry extra hearts for an average of 28 days, and more than 20% of this group then lived for several months.
Shchedlovsky was afraid 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 Eider’s publication, scientist David Felten from Indiana University School of Medicine realized what was criticized in Eider’s work: there was no evidence of a link between the immune and nervous systems. Using a powerful microscope, Felten began tracking nerve endings in open mice. He found that the nerves are connected not only with the blood vessels, but also with the organs responsible for the immune system - with the spleen and thymus gland. After that, Felten moved to the University of Rochester to work with Eider 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 joint work of the brain and the immune system to protect people from disease.
Aider was trying to understand how this knowledge would help patients. A 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 Eder got a call - a 13-year-old girl was desperate for his help.
In 1982, Eider again used conditioned reflexes to treat mice with an autoimmune disease like lupus. He trained them to associate Cytoxan with saccharin solution, as in the original experiment. After creating the association, he continued to give 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 a half dose. It was this study that Marett's mother brought to the doctors.
Karen Olness called Eider and asked if this method could work on Marett. Is it possible to train the immune system to respond to low doses of the drug to save the girl from strong side effects? Aider 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 offers to drink vinegar or liquors, there are chips from eucalyptus. In the end, they chose a combination of fish oil with perfume with a rose aroma.
At an emergency meeting, the hospital approved the treatment, and the next morning the doctors began the experiment. The girl drank fish oil in small 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, Marett continued to drink fish oil and breathe perfume every month, but received a dose 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 bodyreacted to them as well as to the full course . The coagulation factor returned, the pressure returned to normal. After 15 months, the girl stopped drinking fat and breathing a rose, but continued to present the smell of a rose, which, she believed, helped her calm the immune system. The girl graduated from high school and went to college.
At nine in the morning and evening, 46-year-old Barbara Nowak sits at the kitchen table in her house in the city of Sprokhovel in northern Germany with an alarm clock and drinks a powerful cocktail of immunosuppressive drugs. These are 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, due to lupus, she lost both kidneys. 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 changed her life. She had the strength to travel around Europe, participate in geocaching competitions (searching for geocaches by GPS coordinates) with her dog. But there was a flip side to the coin - twice a day she needed to take drugs to suppress the immune system so that her body did not destroy a new organ. And the side effects of these drugs poisoned her along with the kidney. One of them later began to destroy red blood cells.
The woman decided to take part in an experiment at the University of Essen, where Shchedlovsky worked. The Famous Green Drink, as students at Szczedlowski called it, is a new version of the combination of the smell of roses and fish oil that Marett used. Like Eider, Schedlowski wanted to find something memorable and unique, and at the same time stimulated several senses at a time. He took strawberry milk, dyed it green with food coloring and added the essential oil. This drink was tested on a group of healthy volunteers. He replaced the action of the drug CsA by 60-80%.
Novak, along with several other patients, drank her drugs, placebo, and green drink on schedule in 2013. 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 can weaken side effects and, in addition, will make treatment more affordable.
In 1996, Eider gave ten patients with multiple sclerosis, an autoimmune disease, flavored aniseed syrup paired with cytoxane. He later started giving them placebo with syrup, and eight out of ten responded to placebo with immunosuppression just like cytoxan. Shortly before his death in 2011, Eider published a study where a quarter or half dose of an ointment with corticosteroids, after developing a reflex, helped treat psoriasis, as at full dosage.
In 2010, as part of the experimentused a placebo-controlled dose reduction method. Children with Attention Deficit Hyperactivity Disorder (ADHD) were given white-green tablets (placebo) along with conventional medications. At the same time, the children knew that they were drinking a placebo. Later, the dose was reduced, leaving white-green pills. Children in the half-placebo group received better results than children who simply received half the dose. If this method is used in the United States, huge amounts of money can be saved to the budget - only $ 5.3 billion is spent on drugs for ADHD per year.
Reducing the cost of drugs is useful for people who need to be treated, and for the state as a whole. But pharmaceutical companies will do their best to prevent this - or they will have to double the price of drugs to save profits.
Pediatrician Adrian Sandler of Seven Carolina, who conducted the experiment in 2010, would like to continue his experiments by 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 then it was believed that it was independent. Despite the fact that Eider and Felten proved that the same principle applies in immunology, they are little known. Schedlowski, supported by the German Research Foundation DFG, leads 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 nobody else! ”
Sources:
Can the Immune System Be Taught? (Episode from The Mind Body Connection)
You can train your body into thinking it's had medicine
Behaviorally conditioned immunosuppression
Conditioning as an adjunct in the pharmacotherapy of lupus erythematosus.
Conditioned Placebo Dose Reduction: A new treatment in ADHD?
Correspondence N.K. Roerich and S.I. Metalnikova
In 1985, antibodies attacked coagulation factors in the blood. Marett removed the uterus - the girl could bleed during menstruation. Despite many drugs, blood pressure rose. 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 a conditioned reflex not only for the production of gastric juice, as was the case with Pavlov’s dog, but also for the suppression of immunity. The girl was saved with the help of 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, impaired renal function, 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. The psychologist and pediatrician Karen Olness, who worked with Marett, was sure: if the girl copes with stress and pain, then this drug will definitely kill her. And then Marett's mother 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? The fact that you can train the body to respond to the medicine so that in the future it will include the same triggers without the drug. Proponents of this phenomenon hope to reduce the dose of drugs to treat various diseases, including autoimmune and cancer, in order to minimize side effects and reduce the cost.
Pavlov’s dog, Metalnikov’s guinea pigs and Eider’s mouse
Have you ever had poisoning after a meal that you really love? After such an event, you may not be able to touch this dish for several weeks or months. This is called the "conditioned reflex of disgust." In the past, this property helped people survive - they did not try food again, which made them sick.
In 1975, a psychologist from New York studied the conditioned reflex of disgust in rats. Robert Ader of the University of Rochester gave animals water with sugar . Rats love sweets, but for this experiment, Aider combined the drinking process with injections of cytoxan. Then the scientist again gave the rats sweetened water, but they refused it. Therefore, Aider forcefully pipetted the animals, after which they died.
Although cytoxan is toxic, rats have not received a lethal dose. Animals not only learned that they feel bad after sweet water: their body remembered the response of the immune system. The immune response 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 has already been known. It is called the “conditioned reflex”; it was discovered by the Russian physiologist Ivan Pavlov in the 1890s. It was he who divided the totality of reflexes into conditioned and unconditioned. In 1904, Pavlov received the Nobel Prize in medicine and physiology for his work on the physiology of digestion.
Different signals affect the human body every day. They prepare us for food or sex, triggering physiological reactions. Sometimes a person, just knowing that there is a cat in the house, begins to sneeze - 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 it 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 might be trained. Among these researchers was Sergey Metalnikov, zoologist and immunologist. Unlike Eider, 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, in medicine and physiology, the physicochemical theories of immunity have dominated in the main way. Immunity was studied as an autonomous process, which proceeds the main image in the blood. I prove on the basis of a number of experiments on various animals that the nervous system and mental factors play a major role in immunity. I don’t remember if I sent you my last article, Factoures biologique et psychique de l'immunite [17]. I am preparing a book about the "Roles of the nervous system and mental factors in immunity." That is why I am now interested in Yoga. The books you sent didn’t quite satisfy me. Still, it’s not clear to me how the will is raised over one’s own body to such an extent that a person is able to stop an arbitrary beat of the heart or stop bleeding. I am surprised that in India, where there are universities and laboratories, it 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] of 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 bacteria into guinea pigs while warming their skin. He then gave these pigs a lethal dose of cholera vibrio. The pigs, which after the injections did not heat the skin - that is, 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, they forgot about Russian teachings, and Eider’s work was ignored. This is because no mechanism was found by which the animal can remember 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 connected seemed delusional. Scientists were convinced that the immune system responds to physical signals - to infection and injuries - without any help from the brain.
Physiologist from GermanyManfred Schedlowski drew attention to 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. Schedlowski, 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 a CsA drug, which has the effect of immunosuppression similar to Cytoxan. Shchedlovsky found that a response to saccharin without a drug inhibits the growth 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-γ, just like the drug.
Schedlowski continued to search for areas where such a conditioned reflex can be used in medicine. He already thought that this would help people after transplantation, when the recipient's immune system attacks an alien organ. To test his assumption, Schedlowski transplanted second hearts into the abdominal cavity of rats, gave animals sweetened water with ScA, and then removed the drug and gave only water with saccharin. These rats transferred 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 next experiment turned out to be more interesting. The group of rats that received small doses of CsA lived on average 8 days after transplantation. A full course of the drug extended the life of other rats to 11 days. But those rats that developed a reflex and were given small doses of CsA were able to carry extra hearts for an average of 28 days, and more than 20% of this group then lived for several months.
Shchedlovsky was afraid 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 Eider’s publication, scientist David Felten from Indiana University School of Medicine realized what was criticized in Eider’s work: there was no evidence of a link between the immune and nervous systems. Using a powerful microscope, Felten began tracking nerve endings in open mice. He found that the nerves are connected not only with the blood vessels, but also with the organs responsible for the immune system - with the spleen and thymus gland. After that, Felten moved to the University of Rochester to work with Eider 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 joint work of the brain and the immune system to protect people from disease.
Aider was trying to understand how this knowledge would help patients. A 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 Eder got a call - a 13-year-old girl was desperate for his help.
Fish oil and the smell of roses
In 1982, Eider again used conditioned reflexes to treat mice with an autoimmune disease like lupus. He trained them to associate Cytoxan with saccharin solution, as in the original experiment. After creating the association, he continued to give 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 a half dose. It was this study that Marett's mother brought to the doctors.
Karen Olness called Eider and asked if this method could work on Marett. Is it possible to train the immune system to respond to low doses of the drug to save the girl from strong side effects? Aider 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 offers to drink vinegar or liquors, there are chips from eucalyptus. In the end, they chose a combination of fish oil with perfume with a rose aroma.
At an emergency meeting, the hospital approved the treatment, and the next morning the doctors began the experiment. The girl drank fish oil in small 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, Marett continued to drink fish oil and breathe perfume every month, but received a dose 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 bodyreacted to them as well as to the full course . The coagulation factor returned, the pressure returned to normal. After 15 months, the girl stopped drinking fat and breathing a rose, but continued to present the smell of a rose, which, she believed, helped her calm the immune system. The girl graduated from high school and went to college.
Green Strawberry Lavender Milk
At nine in the morning and evening, 46-year-old Barbara Nowak sits at the kitchen table in her house in the city of Sprokhovel in northern Germany with an alarm clock and drinks a powerful cocktail of immunosuppressive drugs. These are 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, due to lupus, she lost both kidneys. 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 changed her life. She had the strength to travel around Europe, participate in geocaching competitions (searching for geocaches by GPS coordinates) with her dog. But there was a flip side to the coin - twice a day she needed to take drugs to suppress the immune system so that her body did not destroy a new organ. And the side effects of these drugs poisoned her along with the kidney. One of them later began to destroy red blood cells.
The woman decided to take part in an experiment at the University of Essen, where Shchedlovsky worked. The Famous Green Drink, as students at Szczedlowski called it, is a new version of the combination of the smell of roses and fish oil that Marett used. Like Eider, Schedlowski wanted to find something memorable and unique, and at the same time stimulated several senses at a time. He took strawberry milk, dyed it green with food coloring and added the essential oil. This drink was tested on a group of healthy volunteers. He replaced the action of the drug CsA by 60-80%.
Novak, along with several other patients, drank her drugs, placebo, and green drink on schedule in 2013. 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 can weaken side effects and, in addition, will make treatment more affordable.
In 1996, Eider gave ten patients with multiple sclerosis, an autoimmune disease, flavored aniseed syrup paired with cytoxane. He later started giving them placebo with syrup, and eight out of ten responded to placebo with immunosuppression just like cytoxan. Shortly before his death in 2011, Eider published a study where a quarter or half dose of an ointment with corticosteroids, after developing a reflex, helped treat psoriasis, as at full dosage.
In 2010, as part of the experimentused a placebo-controlled dose reduction method. Children with Attention Deficit Hyperactivity Disorder (ADHD) were given white-green tablets (placebo) along with conventional medications. At the same time, the children knew that they were drinking a placebo. Later, the dose was reduced, leaving white-green pills. Children in the half-placebo group received better results than children who simply received half the dose. If this method is used in the United States, huge amounts of money can be saved to the budget - only $ 5.3 billion is spent on drugs for ADHD per year.
Who against
Reducing the cost of drugs is useful for people who need to be treated, and for the state as a whole. But pharmaceutical companies will do their best to prevent this - or they will have to double the price of drugs to save profits.
Pediatrician Adrian Sandler of Seven Carolina, who conducted the experiment in 2010, would like to continue his experiments by 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 then it was believed that it was independent. Despite the fact that Eider and Felten proved that the same principle applies in immunology, they are little known. Schedlowski, supported by the German Research Foundation DFG, leads 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 nobody else! ”
Sources:
Can the Immune System Be Taught? (Episode from The Mind Body Connection)
You can train your body into thinking it's had medicine
Behaviorally conditioned immunosuppression
Conditioning as an adjunct in the pharmacotherapy of lupus erythematosus.
Conditioned Placebo Dose Reduction: A new treatment in ADHD?
Correspondence N.K. Roerich and S.I. Metalnikova