In the case of age-related diseases, such as heart disease or dementia, it can be argued that in the past no one has lived long enough to have them. It can also be argued that since these diseases affect humans after reproductive age, natural selection has bypassed degenerative senile diseases.
However, this argument does not work for autoimmune diseases, which usually affect a person in the Prime of life, in their twenties or early thirties, or even earlier. Although such diseases do not kill a person immediately, they usually have a negative impact on their physical condition. Even those symptoms that at first glance may seem insignificant, entail serious consequences. I have often thought about how, for example, losing my eyelashes as a result of universal alopecia would have affected my ability to survive 20,000 years ago. A deer appears in my field of vision, and suddenly-Bang! “I’m getting a fly in my eye.” The loot is lost. The tribe is starving. Fertility is declining. Genes don’t pass through natural selection. (And in fact in this scenario is not taken into account my asthma. I should have taken good aim, for I could not have chased a wounded deer for long.)
Everything matters, even the eyelashes. It could be assumed that, given enough time, natural selection would eliminate from the human genome those genes that cause harmful disorders of the immune system. However, the opposite has actually happened — genes that cause predisposition to diseases such as type 1 diabetes, Crohn’s disease, psoriasis, lupus, and celiac disease have become more common over the past 30,000 years.
Population geneticists Luis Barreiro and Lluis Quintana-Murci argue that increased crowding at the end of the Paleolithic and Neolithic periods led to an increase in the number of gene variants associated with autoimmunity. In a later period, higher exposure to new animal-transmitted diseases also increased the pressure of natural selection. In other words, the higher the crowding and the more the living conditions contributed to the spread of infection, the more useful these genes became. In all likelihood, the benefits of having such enhanced protection tools have always outweighed the negative effects of autoimmune diseases. Or maybe these genes, as the results of the above-mentioned studies show, did not cause so many autoimmune diseases in the previous conditions.
Celiac disease (an inflammatory bowel disease that causes the protein gluten found in wheat, oats, and other cereals) allows a thought experiment to test this assumption. After the birth of agriculture, natural selection favored four of the nine gene variants associated with celiac disease. Why is the number of genes that determine predisposition to a disease caused by the food that is becoming more common increasing? This may be because these genes did not cause the above-mentioned disease to the same extent in the past. In fact, even 60 years ago, celiac disease was diagnosed in a much smaller number of people.
Type 1 diabetes is an even more striking example. One study found that 58 of the 80 gene variants associated with this disease have become more common over the past few millennia. Autoimmune diabetes usually begins in childhood, and before scientists developed insulin in the 1920s, the disease was probably fatal in all cases without exception. There is a strong negative factor in the pressure of natural selection, than death before the appearance of the offspring. Therefore, if these genes always caused as many cases of type 1 diabetes as they do now, they would quickly exclude themselves from the human genome. But this did not happen. They have become more common. In this case, we can again conclude that in the past, these genes did not create the same vulnerability to autoimmune disease as they do today.
As we have seen, scientists have a pretty good idea of how these gene variants enhance immunity. Patients with lupus are surprisingly easy to cope with malaria. Apparently, the same thing happens to the inhabitants of Sardinia. What about type one diabetes? Finnish children whose immune systems contain genes that predispose them to this disease also have the ability to fight-no, not malaria, but microbes that enter the body through the gastrointestinal tract, such as Coxsackie virus and polio virus [124]. And mice with type 1 diabetes are adept at coping with infectious diseases caused by bacterial parasites, such as the pathogen Mycobacterium tuberculosis (Koch’s wand). (As in the case of malarial infection in predisposed to lupus mice, mycobacterial infection prevents autoimmune disease in mice prone to diabetes.)
The same genetic predisposition that leads to type 1 diabetes today probably gave people the ability to skillfully repel attacks from intracellular pathogens in the past. More generally, all these observations suggest that the genes underlying autoimmune diseases are not the result of random mutations. They should not be considered a bad purchase. They are part of a very specific set of genetic tools that have evolved to help us survive in an increasingly polluted world.
So why don’t we boost the immune response? It turns out that there is a limit to how far mammals can go. Take the wild sheep of the St. Kidd’s archipelago, off the North-West coast of Scotland, as an example. For decades, scientists have carefully studied the life of a herd of 500 individuals on one of the Islands. Not so long ago, they analyzed blood samples taken from these animals over a decade, paying particular attention to autoreactive antibodies — a predictor of autoimmune diseases in modern “domesticated” humans. Then they compared the results with the level of reproductive success of these animals.
As a result, the researchers found that in the wild, autoreactive antibodies provide noticeable benefits. During the harshest winters, more than half of the animals in the herd died. However, animals with a large number of autoreactive antibodies survived better in harsh conditions and under high parasitic load. This was direct evidence of the benefits of being prone to autoimmune diseases. However, despite the absence of autoimmune diseases in active form, another drawback became apparent: sheep with this “autoimmune” tendency had fewer lambs. An effective immune system had its price: fewer offspring.
Rudy Westendorp, a Professor of gerontology at Leiden University, explained this dynamic to me. In the case of mammals, especially such as Homo sapiens, which have a long gestation period, the more unstable and prone to inflammation the immune system is, the more likely it is to affect the reproductive process. In essence, the embryo is an alien organism that has taken up residence in the mother’s body. Therefore, the mother’s immune system must maintain a delicate balance between tolerance for fetal development and maintaining sufficient “firepower” to destroy pathogens. In this regard, there is an upper limit to how ruthless the mammalian immune system can be — a threshold beyond which the power of the immune system begins to have a negative impact on reproductive success.
“When you go into a Pro — inflammatory mode, it has a negative effect on your physical condition, “says Westendorp,” and natural selection doesn’t allow it.”
Now imagine those wild sheep living in a parasite-free London flat — in a clean, modern environment conducive to an idle, passive lifestyle. You can be sure: without activation of the immune system under the influence of infectious agents, these long-living sheep will start autoimmune diseases. Why? Because real infectious agents activate the immune system in a very specific way. They induce the suppressor cells discussed in Chapter 1.