By MIKE MAGEE
In 1872, the English mathematician and sometimes poet, Augustus of Morganwrote this catchy rhyme: “Big fleas have little fleas on their backs to bite them, and little fleas have little fleas, and so on ad infinitum.”
This truism about interspecies competition for access to nutrition and reproduction might have served Napoleon well 60 years earlier, when he tragically underestimated his enemies’ will to live. It was not so much the stubborn Russians but the microbes that were their undoing.
When he launched his invasion with a staggering force of 615,000 men, 200,000 horses and 1,372 mobile guns, he seemed unstoppable. But on his way to Moscow (according to Tolstoy’s account of the misfortune in “War and Peace”) lost 130,000 men to Shigella dysentery. Faced with inclement weather and a Russian force that refused to participate in the defense of Moscow, Napoleon lost 2/3 of his remaining forces in retreat at the hands of Typhus, led by Rickettsia prowazekkilodged in body lice embedded in the rancid clothing of his soldiers.
Under more favorable circumstances, the soldiers’ immune systems would have been their ally. Human bioengineering has evolved alongside pathogenic microbes determined to chemically outcompete their human hosts.
Humans rely on innate and adaptive mechanisms to detect and destroy pathogens. But to do so without damaging their own cells, they must be able to distinguish I of not-I. And they must adapt and remember, producing long-lived immune cells and protein receptors that allow them to “capture” and destroy repeat offenders.
If the system experiences a failure in self-tolerance, protective processes can be overwhelmed and result in a chronic inflammatory response that destroys healthy tissues and marks the onset of autoimmune diseases.
A special circumstance Where immune tolerance is normal and essential is maternal self-suppression during pregnancy, which allows two separate immune organisms to survive intimate relationships side by side.
At four weeks into pregnancy, the small developing fetus is already developing cells that will eventually differentiate into immune blood cells. By the third month of pregnancy, these cells travel through blood channels to the liver, spleen, and thymus. Some of them (B cells in the bone marrow and T cells in the thymus) are already functional, but they are not necessary. the uterus is sterile. By 19 weeks, immune cells have also distributed to the intestinal lymph nodes.
Mothers and babies are not genetically identical. And yet, the mother’s immune system protects developing fetal cells. While in the sterile uterus, fetal cells do not require an active immune system of their own. Furthermore, by the fourth or fifth week of development, the fetus has seeded the mother’s circulatory system with fetal cells, which are tolerated and not rejected as foreign. Studies have shown that up to 0.1% of a mother’s adult cells can be genetically assigned to her child. This is called “microchimerism.”
While the child is in the womb, its immune system sleeps and the mother tolerates its occasional exposure to fetal cells as benign and acceptable. All that changes at birth.
The newborn child is “immunogenously naïve” and at risk as it passes through the bacteria-rich vaginal canal. That does not mean that the child is unarmed. From 13 weeks onwards, the mother’s antibodies cross the placenta and reach the fetus. By the end of the third trimester, these are abundant. Mother’s breast milk/colostrum is also rich in antibodies and immunologically active cells, granules and enzyme fluids. These provide immediate, short-lived immune protection and a chance to catch up. But the supply of rapidly responding neutrophils is limited in this two-month process, and the newborn is vulnerable to a variety of infections, especially Streptococcus, Staphylococcus, Klebsiella Hemophilis influenza and Meningococcus.
When the baby’s immune system is activated (after 2 months), each pathogen is new. It has no memory until adaptive immunity (in the form of B and T cell lymphocytes) generates specific antibodies and immunoglobulin receptors that can mark future invaders for destruction. This is why pediatricians instruct new parents that any fever before two months of age requires an immediate examination.
It is fair to say that there is still much to understand in the field of immunology. But researchers believe that further studies of fetal immunity could trigger a series of new discoveries. “Fetal allograft tolerance” undoubtedly carries great academic interest. But many believe that understanding the intricate chemical and physiological systems that make this possible could lead to clinical advances in cancer therapy, the treatment of autoimmune diseases, and the prevention of degenerative inflammatory diseases that accompany aging.
Increasingly, leading research immunologists are challenging the very foundations of self-identity that have anchored the discipline. Consider these words directed at the long-standing “self versus non-self” theory from a May 2025 post on Frontiers in immunology:
“Its partial obsolescence is, in fact, a tribute to how far immunology has come. As we advance deeper explorations of microbiome-immune interactions and epigenetic plasticity, the field will undoubtedly continue to change. The fundamental question of how an organism maintains its integrity in a constantly changing environment of microbes, tissues and signals remains as relevant as ever, but the answers we seek must match the complexity and dynamism of biological reality. If this means embracing the ‘end of a dogma,‘It also heralds the dawn of a more integrative immunological science.’
Are humans smart enough to realize all this? Maybe not.
But Anthropic CEO Dario Amodei who used to be a biomedical researcher, switched to AI to give humans an advantage over Morgan’s fear of Augustus. As he recently said, “One of the observations I had the most when I worked in that field was the incredible complexity of it. And I had this feeling of: Man, this is too complicated for humans. We are making progress on all these problems in biology and medicine, but we are doing so relatively slowly. So what attracted me to the field of AI was this idea: Could we move faster?
Mike Magee MD is a medical historian and regular contributor to THCB. He is the author of CODE BLUE: Inside America’s medical industrial complex. (Arboleda/2020).
