Throughout history, humanity has suffered from various infectious diseases and fought against them. For thousands of years, epidemics of plague and cholera terrorized the civilized world. Thanks to modern advances in hygiene and medicine, these enemies have been defeated. But have we lost something important along the way?
The human body is imperfect. We age, get sick, and die. If in the Stone Age the leading causes of death were trauma, starvation, and wild animals, and in the Middle Ages it was plague and cholera, now, according to the World Health Organization, it is cancer and cardiovascular disease. And if we look at scientific budgets and the distribution of grants in biomedicine, we see that the word “cancer” in an application significantly increases your chances of receiving funding.
However, there are diseases that may not be as deadly but have a much greater economic impact on us. These are autoimmune diseases such as multiple sclerosis, systemic lupus erythematosus, and type 1 diabetes. While cancer and strokes are most common in older people, autoimmune conditions usually manifest (appear as symptoms) in young people of working age and either place a heavy burden on the country's budget or the patient, or, as in the case of multiple sclerosis, simply put an end to the patient's career and life.
The peculiarity of autoimmune diseases is that, after many years of research and experimentation, we have not learned how to achieve lasting remission for virtually any of them. Current solutions boil down to either supportive therapy (as in the case of insulin-dependent diabetes) or attempts to delay the terminal stage of the disease, which is the goal of multiple sclerosis drugs. Until recently, the situation looked pretty dire. It is further exacerbated by the fact that the number of people with autoimmune diseases is growing every year, and we are on the verge of a real epidemic.
However, where the pharmaceutical industry has suffered one failure after another, nature itself has suddenly shown researchers where to look and where to find a truly effective cure.
Background
To understand where the problem with autoimmune diseases came from, we need to look far back into the past.
All of humanity's progress can be considered, with a certain degree of approximation, a race against death. Paleolithic hunters suffered from disease or starvation and died at the hands of predators. The response was the domestication of fire, the development of more effective tools, and the transition from unpredictable and dangerous hunting and gathering to sedentary life and agriculture. In epidemiology, this process is commonly referred to as the “first epidemiological transition.”
The goal of the transition was largely achieved. Living in wooden and then stone houses meant that people no longer had to fear predators. Agriculture, while not providing 100% protection, did protect against starvation. Quality of life and life expectancy increased significantly. But the old killers were replaced by new ones. The fact is that one of the most significant consequences of the “transition” was epidemics, which humanity had not known before.
This was due to the change in human lifestyle during the FET. Before that, we lived in small groups of no more than 50 individuals, occupying fairly large areas. In addition, we constantly changed our place of residence and never stayed anywhere for long. Hygiene standards were quite low — why keep your shelter clean if you have already eaten all the mammoths around and will have to find a new place tomorrow?
During FET, people began to stay in one place for a long time, forming larger groups to protect themselves from raids by fellow tribesmen. Overcrowding and pollution of the habitat created optimal conditions for the development of infections. Epidemics began, which were all the more fierce the larger the city was and the more densely populated it was. It took humanity quite a long time, about 5,000 years, to learn how to deal with infections. Somewhere earlier, somewhere later, people realized the importance of hygiene for life and health. Cures for many diseases were found empirically. It can be said that all progress in medicine and humanity as a whole took place under the constant fear of new epidemics.
All this could not but affect our cultures and behavior. Many world religions have included hygiene requirements since the beginning of the historical period. Just think of the Egyptian priests, who shaved their entire bodies daily and constantly cleansed them of any dirt. In many cultures, the word “unclean” is synonymous with ‘bad’ or “someone to be avoided.” The inseparability of death from disease has taught us to fear any impurity, any signs of illness.
Today, we are cleaner than we have ever been in history. This is especially evident in developed countries. We are used to having running water in all our homes and always being able to take a bath or shower. We use soap, wet wipes, and antiseptic gels. In some countries, they even wash the roads with shampoo!
It would seem that cleanliness is a good thing, so what's the problem? What does this have to do with autoimmune diseases? It turns out that there is a direct connection.
The hygiene hypothesis
The first hints of what scientists today call the “hygiene hypothesis” or “old friends hypothesis” appeared in scientific literature as early as the late 19th century. This period in the history of immunology is called the Second Epidemiologic Transition, or SET. It is characterized by a sharp decline in the incidence of various infectious diseases (bacterial and helminthic), as well as a much rarer transition of these diseases into epidemics. Take the plague, for example. We all know how much it affected the fate of Europe in the Middle Ages. But how many people know that it has not been completely defeated? In 2015–2024, epidemic manifestations of the plague were recorded in ten countries. The total number of cases was 5,880, of which 582 were fatal (over 10 years). Note that there was no epidemic. Outbreaks are quickly localized, patients receive adequate treatment, and almost everyone recovers. The “Black Death” no longer frightens anyone.
This transition was made possible by the advent of antibiotics and other highly effective antiparasitic drugs. In developed countries, it was completed by the end of the 20th century. While in the middle of the century, every third inhabitant of Europe was infected with helminths, today it is rare to find a carrier of these parasites. Urban lifestyles, centralized purified water supplies, food quality control, and so on have also contributed to this decline.
However, since the 19th century, evidence has begun to emerge that modern urban lifestyles and general well-being (usually accompanied by increased “cleanliness” of life) lead to certain diseases. A typical Victorian aristocrat was sure to have several “social” diseases, such as “hay fever” or, as we call it now, pollen allergy. A more serious “disease of the rich” was type 1 diabetes, which was the scourge of “affluent society” until the discovery of the healing properties of insulin.
These diseases appeared suddenly and quite recently in human history—200 years ago, they either did not exist or were so rare that they left no trace in medical literature. The link between the emergence of these diseases and the living conditions of patients was first established by David Strachan in 1989 in a short note in which he postulated the “hygiene hypothesis.” He noted that people who had fewer siblings in childhood were more susceptible to hay fever. Strachan suggested that resistance to hay fever is transmitted from sibling to sibling (brothers and sisters) through childhood infections and is a consequence of reduced hygiene.
Subsequently, many researchers have shown the same thing with other allergies and autoimmune reactions. For example, if children from regions with poor hygiene, such as Chile or Thailand, undergo a European deworming program, they develop a host of allergies.
Perhaps the most interesting example here is the story of multiple sclerosis. Scientists decided to see what happens when a patient with this terrible disease becomes infected with helminths and began to look for MS patients infected with worms. The results were stunning. In patients who were infected with certain helminths (for example, Trichuris trichiura), the course of the disease practically stopped. During the infection, the number of new plaques in their brains decreased by 95%. This result cannot be achieved by any modern method of therapy! If, for some reason, the helminths had to be removed (for example, due to the development of acute inflammatory bowel disease), the disease resumed at the stage at which it had stopped during infection. It can be said that the hairworm maintained the health of these people, allowing them to lead a normal life as long as they allowed it to live inside them. So what is happening? How do worms cope with a task that modern medicine is unable to cope with? To answer this question, we need to understand how our immune system works.
Immune response
The immune system is designed to protect the body from internal and external enemies. External enemies are viruses, bacteria, protozoa, and worms that constantly enter our body and are destroyed at the front lines. Internal enemies are cancer cells, as well as cells infected with viruses or intracellular bacteria.
The key concepts for immunity are “antigen” and “inflammation.” An antigen is any molecule that the immune system can recognize and attack. Virtually anything can be an antigen. Inflammation is the tissue's response to damage or the threat of such damage. Molecules that trigger inflammation are called pro-inflammatory, while those that block it are called anti-inflammatory.
When a parasite enters the body, it is first encountered by the innate immune system, whose cells (macrophages) are found in all tissues. In this case, the antigens are molecules that are foreign to our body — the cell wall of bacteria, the double-stranded RNA of some viruses, our DNA floating freely in the intercellular space, and so on. When intruders are detected, the cells of the innate immune system attempt to destroy them, while simultaneously releasing pro-inflammatory molecules. The inflamed tissue blocks the parasite's exit from the site of entry into the rest of the body and attracts new immune cells to the site of damage.
If the innate immune system fails to destroy the invaders, the adaptive immune system takes over. This does not happen immediately: the activation of the adaptive response is preceded by 3-4 days of preparation in the lymph nodes (during which the lymph nodes increase in size, which is a sign of an infectious disease). It all starts when some of the innate immune cells arrive at the lymph node, carrying antigens from the site of infection. In this case, the antigens are short (8 to 20 amino acids) peptides from the proteins of the infectious agent and surrounding tissues. In essence, a macrophage (or a specialized activator of adaptive immunity — a dendritic cell) simply captures samples of dissolved proteins, fragments of the parasite, and dead cells from the site of inflammation and brings them to the lymph node.
In the lymph node, they are encountered by naive (unactivated) adaptive immune cells — T lymphocytes. Each lymphocyte, leaving the site of its formation, carries a unique receptor that is formed by targeted mutations in the genome. It is not known in advance whether this receptor can recognize any antigen, but there are so many variants of it (according to some estimates, we may have up to 1048 different types of this receptor, but most of them will be non-functional) that within a few hours, at least several cells capable of recognizing the parasite's antigens are detected in the lymph node. These cells then divide, activate, and travel to the damaged tissue, where they search for their antigens and destroy both the invaders themselves and the infected cells, if we are talking about a virus or intracellular bacteria. The immune system is the only system in the body whose task is to destroy other living beings—individual cells or multicellular organisms. Moreover, our own cells must also often be destroyed if they are infected with a virus or bacteria or have become cancerous. At the same time, it is necessary to avoid an immune response to normal cells. If such a response develops, an autoimmune disease occurs.
To prevent this, our body has a system for creating immunological tolerance — protecting “its own” from the immune system. Central tolerance consists in destroying, during development, those T-lymphocytes that have mutated their receptors so that they can recognize and attack their own antigens. Some of these lymphocytes transform from killers into defenders (so-called regulatory T lymphocytes) — they recognize their own antigens and suppress any immune response against them.
Peripheral tolerance occurs when a T lymphocyte recognizes an antigen in the lymph nodes, but there is no inflammation at the site where the antigen entered the lymph node. On the contrary, there is a high concentration of anti-inflammatory molecules. Such a lymphocyte is again either destroyed or transformed into a regulatory one.
Parasites and symbionts
For billions of years of evolution, large multicellular organisms have been home and food for smaller unicellular and multicellular organisms. Humans are no exception — after all, we are both a good source of food and an excellent protector for everything that manages to settle inside us or on us.
Evolution has divided these cohabitants into two large groups — parasites and symbionts. Parasites rely on rapid reproduction. They have the ability to suppress innate immunity, and by the time adaptive immunity is activated, they have already managed to reproduce using our resources and spread the infection further. This is how the influenza virus or bacterial pneumonia works, for example.
Symbionts, on the other hand, have learned to suppress both innate and adaptive immunity. To do this, they had to moderate their appetites — if the body's cells are constantly damaged, no tricks can prevent the activation of immunity. Therefore, they settled on the surfaces of our body, primarily on the surface of the gastrointestinal tract, where they receive only a part of our food, but do not attack the body itself.
In addition, they have learned to suppress inflammation by secreting substances that are similar to our anti-inflammatory molecules. Macrophages of the innate immune system, when encountering such bacteria, can sense the antigens of the cell wall, but are not activated because they are suppressed by the anti-inflammatory background around them.
The third defense mechanism is antigenic mimicry. For adaptive immunity, the main antigens are peptides from proteins. And many of our symbionts have changed their protein composition over the course of evolution so that it contains as many peptides as possible that are similar to ours. In this way, they come under the protection of regulatory lymphocytes. This mechanism is characteristic of all types of our cohabitants — bacteria, worms, viruses, and so on.
For millions of years, every individual of our species, upon birth, immediately came into contact with symbionts inhabiting the skin, mucous membranes, and intestines of their fellow creatures. Over time, the body learned to benefit from this constant, unavoidable coexistence. In particular, the ability of bacteria and worms to create a strong anti-inflammatory background in their habitat has become a key factor in the development of peripheral tolerance. It spread to both the antigens of the cohabitants themselves and those associated with them — food antigens (in the intestines), dust and pollen (in the lungs), and the body's own antigens (the very antigens that the cohabitants developed in the course of antigenic mimicry).
And again, the hygiene hypothesis
Attentive readers will already have grasped the connection here. The peculiarity of the second epidemiological transition is that we are cleaner than ever before, free of virtually all helminths and many pathogens. Children no longer see their first dirt or puddle in the first days of life, as they did in the past. Antibiotics and hygiene rules, central water supply, and washing asphalt with shampoo have undoubtedly made our lives better. But unnoticed by ourselves, along with the “dirt,” we have also begun to eliminate from our lives some of the very symbionts, worms, and bacteria (and, according to some scientists, certain viruses) that helped us develop tolerance to our own bodies and environmental allergens.
We already have evidence that infection with certain types of symbiotic flora leads to a decrease in the incidence of many autoimmune diseases. This is precisely the flora that is widely present in third world countries and almost absent in developed countries. The example of “stopping” multiple sclerosis is only the most striking, but there are many more such examples. It has been shown that in patients infected with this now-expelled “parasite,” the number of regulatory T cells increases, as does the concentration of anti-inflammatory molecules. Expelling the symbiont reverses everything. Some symbionts have been found to be strongly associated with diabetes, others with multiple sclerosis, and so on.
The first year of life has a particularly strong influence on the risk of developing such diseases. If during this period a child spends some time in large groups of peers (in a hospital or kindergarten, school) and generally encounters infections more often, the risk of developing autoimmune diseases is seriously reduced.
Of course, it is not only the microbiome (the totality of all symbiotic microorganisms of a particular person) and helminths that influence the risk of developing autoimmune and allergic reactions. There is also genetic predisposition and the conditions in which a person first encounters a particular external antigen. There are some microorganisms that do not protect, but rather provoke autoimmune diseases. For example, streptococcus can cause rheumatism, and some staphylococci produce a superantigen that nonspecifically triggers all T-lymphocyte clones with any receptor — this can also lead to autoimmune diseases.
But exceptions only prove the rule. The ability of symbionts and parasites to influence, positively or negatively, the development of autoimmune diseases is already a proven fact. Doctors and scientists do not yet know what to do with this information. We tried to obtain worm homogenates and use them as medicine. It did not work. Immunologists are figuring out the mechanisms by which worms achieve what is unavailable to all doctors in the world, while doctors and pharmaceutical companies are developing innovative methods of therapy. As of 2025, more than 30 clinical trials of “helminth therapy” have been conducted worldwide, in which patients take a dosed suspension of live worm eggs obtained under sterile conditions from the best pharmaceutical manufacturers. Despite promising results, problems remain. For example, worms often have to be removed due to developing inflammatory bowel disease. But we don't have a better option yet.
What should we do while scientists piece together this mystery and search for a solution? The pursuit of absolute cleanliness of hands and body is not entirely correct, but at the same time, we cannot not wash our hands, we cannot not wash, for example, fruit, the surface of which is often contaminated with hepatitis A, which, when ingested through the mouth, can have serious consequences for humans. The task of scientists and ordinary people is to find a balance, an optimal middle ground.
However, many of us have developed excessive habits in our lifestyles that seriously disrupt the immune system, affecting the very symbionts that benefit the human body. For example, frequent use of antiseptic alcohol-based gels; uncontrolled intake of antibiotics; use of antibacterial soap instead of regular soap, and daily use of such products, especially by children, can cause much more damage than the flu or food poisoning.