In the summer of 1995, Joel Weinstock got stuck on a plane that wasn’t going anywhere. A thunderstorm raged over the Chicago area, which caused the return flight to Iowa city to be postponed indefinitely. It was an unpleasant experience, but being on a plane without any distractions (such as phone calls or articles to finish) provided a welcome respite.
Weinstock, as a gastroenterologist, attended a conference in new York on inflammatory bowel diseases, which he specialized in and which were the focus of this field of medicine. In addition, Weinstock was just writing a Chapter on inflammatory bowel diseases for a book on autoimmune diseases that was soon to be published, so his mind was preoccupied with finding an answer to a long-standing question: why has the prevalence of inflammatory bowel diseases increased significantly over the past 50 years? In some population groups, the rate has increased from one case per 10,000 people to one case per 250 people — a forty-fold increase over two or three generations.
There are two types of inflammatory bowel diseases: Crohn’s disease that affects the small intestine but may also affect any area of the bowel and ulcerative colitis, a disease of the colon — large portion of intestine that ends with anus. It was found that for some reason in a certain population group, the number of cases of ulcerative colitis first increases, and then there is a surge in the incidence of Crohn’s disease. The symptoms, which include bloody diarrhea, weight loss, anemia, eating disorders, and in some cases death, were similar to those of a gastrointestinal infection. However, scientists have yet to isolate a bacterium or virus that causes inflammatory bowel diseases. In fact, chronic inflammation in the absence of a clear, well-founded target is the defining characteristic of inflammatory bowel diseases: “flamethrower” is enabled, but the enemy is not in sight. This can lead to serious negative consequences, such as the build-up of scar tissue that prevents the movement of digested material, blood loss and anemia, and even the gradual thinning of their own tissues, which results in an opening (fistula) leading to other areas of the abdominal cavity.
First of all, it should be noted that the intestines are not sterile. It is home to a large community of microorganisms, some of which synthesize important substances for the host, such as folate and vitamin K. today, scientists compare the diversity of the intestinal ecosystem with the ecosystem of the rainforest, but in the 60s they were expressed less poetically. Nevertheless, scientists recognized that the human body is home to many bacteria. According to one theory, intestinal inflammation is the result of the immune system mistaking commensal bacteria for deadly enemies. In other words, the disease that leads to progressive self-destruction is due to one of the cases of misidentification.
Geneticists have struggled to detect the genes that cause a predisposition to inflammatory bowel diseases . However, the genetic explanation never seemed right to Wainstock. He believed that the geographical and temporal variability in the occurrence of inflammatory bowel diseases gives good reason to assume that there is some environmental factor. The increase in the prevalence of such diseases occurred in just half a century — a scanty time from the point of view of evolution. The ” bad ” genes couldn’t have spread so quickly. An important discrepancy was also found in the study of identical twins. In particular, it was found that if one twin has Crohn’s disease, the probability of developing This disease in the second twin is 50%. In the case of ulcerative colitis, the compliance rate was even lower — 19%. Obviously, when it comes to inflammatory bowel diseases, genes do not determine a person’s fate.
Sitting on the plane, Weinstock analyzed the development of events in this area in reverse order, right up to the very beginning . In the 1830s, a doctor at the mount Sinai medical complex in new York city, Barril Bernard Krohn, described a disease that eventually became known as”Crohn’s disease”. All fourteen of the first patients were Jewish. History has since shown that inflammatory bowel diseases can affect people of any nationality, but Weinstock put the question this way: what if the high prevalence of this disease among Jews in new York 60 years ago is the key to the cause of its occurrence?
Other scientists have directly linked inflammatory bowel diseases, which usually affect people in their third or fourth decade of life, with the socio-economic situation of a person in their younger years. It has been found that the cleaner conditions a person lives in as a child, the more likely they are to develop inflammatory bowel diseases in adulthood . The presence of running water and flush toilets in childhood increased the risk of intestinal inflammation in later years. Drinking water from a well or stream and defecating in latrines (or in bushes) reduced this risk. Of course, all these pure conditions are signs of material well-being. But what if it is wealth that causes the predisposition to this disease?
When an hour’s flight delay turned into two hours, and two hours turned into four, Weinstock decided to conduct a thought experiment. He imagined holding a mirror in front of a map of the prevalence of inflammatory bowel disease in the United States. As a rule, this indicator increased as you moved from South to North. However, the mental picture that Weinstock created in his mind now showed the opposite pattern — an increase in the prevalence of inflammatory bowel diseases from North to South. Weinstock went even further: instead of asking what factors can cause intestinal inflammation (for example, pollutants, medications, or food), he asked what can prevent this disease. Weinstock wondered if some factor that protected people from developing inflammatory bowel disease had disappeared.
During this period, in addition to writing a book on autoimmune diseases, Weinstock also edited a book on parasites. He spent more than a decade studying a flatworm called the intestinal Schistosoma (Schistosoma mansoni). This parasite is a real miracle of evolution. Microscopic torpedo-shaped larvae of S. mansoni with forked tails wait for their prey in fresh water. Having penetrated through the skin of a person who swims in a pond or wades it, these larvae move through the bloodstream, stop in the lungs or liver, and then settle down for mating (during which the female settles in a special recess in the male’s body) in the blood vessels of the bladder and colon. The fertilized schistosome eggs are then excreted along with the host’s feces and urine.
These eggs, which sometimes get stuck in the liver and other organs, can cause permanently inflamed spherical lesions-granulomas. Such lesions, very similar to inflamed ulcers in the case of Crohn’s disease, have become an excellent model for scientists to study inflammatory bowel diseases. However, in many other parameters, the infectious disease caused by the pathogen S. mansoni differs significantly from intestinal inflammation. For example, flukes can live in the human host for decades, but, with the exception of rare cases of granuloma due to Schistosoma eggs, prolonged stay of one large (about a centimeter long) organism inside another causes much less inflammation than one might expect.
In the process of editing a book about parasites, Weinstock struggled to come up with something terrible to say about these and other helminths, but he failed. A third of the world’s population still had helminths, and the vast majority had no symptoms. Even more people were exposed to helminths at one time or another (most likely in childhood). Weinstock believed that parasites are relatively harmless if you eat well and if you don’t have too many of them.
At this point, all three seemingly disparate pieces of the puzzle (surprisingly harmless parasites, suggestive patterns of inflammatory bowel disease, and the mysterious increase in the prevalence of this disease in the twentieth century) formed a single picture. On the inverted map that Weinstock imagined, the protective factor became more pronounced as we moved from North to South, and this pattern coincided with the prevalence of helminths in the United States in the past. The incidence of intestinal inflammation increased over the past period simultaneously with the destruction of helminths. Weinstock thought that in the past, infection caused by helminths protected against inflammatory bowel diseases.
Back in Iowa, Weinstock discussed the idea with two of his colleagues, gastroenterologists David Elliott and Robert summers. From the point of view of immunology, the idea that helminth-induced infection can prevent inflammatory bowel diseases immediately seemed quite reasonable . At that time, it was believed that there are two types of immune response: one is provided by T-helpers of the first type (Th1), and the other is provided by T — helpers of the second type (Th2). The Th1 immune response directs the immune system’s defense cells to fight off bacteria or viruses (such as Salmonella or smallpox) that try to take over your cells. The second type of immune response, which is referred to by the abbreviation Th2, is aimed at fighting much larger multicellular parasites, such as helminths and blood-eating insects. Painful red swelling around a wound or pustule is a manifestation of the Th1 immune response, and an itchy red bump from a mosquito bite is a typical manifestation of the Th2 immune response. Immunologists believed that these two types of immune responses were mutually exclusive. If you turn on one immune response, the other will turn off, and Vice versa. Gastroenterologists have considered inflammatory bowel diseases as the result of an overactive Th1 immune response. The introduction of helminths in such a situation would presumably enhance the Th2 immune response and disable chronic inflammation, which is responsible for the Th1 immune response that contributes to the development of the disease.
At this point, the essence of the idea was formed, which in many ways contradicted the trends of Western medicine that developed after the victory of the microbial theory a century earlier. The microbial theory States that diseases are caused by infectious agents. Eliminate the microorganism that causes the disease, or prepare the immune system through vaccination-and this will allow you to cure or prevent this disease.
However, Weinstock offered both a more complex model of the origin of inflammatory bowel diseases and a different type of treatment. He knew that parasites had a great effect on the host’s immune system. Until recently, they were a constant element in the evolution of humans and, in all likelihood, all mammals. Weinstock claimed that over millions of years of coexistence, the human immune system adapted to the presence of parasites and even began to rely on them. Consequently, the sudden disappearance of parasites in the twentieth century brought the immune system out of balance. One of the consequences of the resulting imbalance was a higher predisposition to inflammatory bowel diseases. In other words, this disease is caused not by infectious agents, but by their absence. And neither vaccines nor antibacterial drugs will solve this problem. In order to do this, you will need a kind of ecosystem restoration.
“Hygiene has made our lives better,” says Weinstock. — However, in the process of eliminating ten or twenty factors that caused us to get sick, we got rid of the effects of those factors that made us healthy.”