By MIKE MAGEE
In 1872, English mathematician and sometimes poet, Augustus de Morgan, wrote this catching rhyme: “Great fleas have little fleas upon their backs to bite ‘em, And little fleas have lesser fleas, and so ad infinitum.”
This truism about competition among species for access to nutrition and reproduction could have come in handy to Napoleon 60 years earlier when he tragically underestimated his enemies will to live. It wasn’t so much the stubborn Russians as it was microbes that were his undoing.
When he launched his invasion with a staggering force of 615,000 men, 200,000 horses, and 1,372 mobile guns, he appeared unstoppable. But on his way to Moscow, (according to Tolstoy’s account of the misadventure in “War and Peace”) he lost 130,000 men to Shigella dysentery. Confronted with harsh weather and a Russian force that refused to engage in defense of Moscow, Napoleon lost 2/3 of his remaining retreating force to Typhus, carried by Rickettsia prowazekki, housed in body lice embedded in his soldiers rancid clothing.
Under more favorable circumstances, the soldiers immune systems would have been their ally. Human bioengineering has evolved side by side with pathogenic microbes determined to chemically out smart their human hosts.
Humans rely on innate and adaptive mechanisms to detect and destroy pathogens. But to do so while sparing their own cells, they must be able to distinguish self from non-self. 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 breakdown in self-tolerance, the protective processes may over-shoot and result in a chronic inflammatory response that destroys healthy tissues and marks the emergence of auto-immune diseases.
One special circumstance where immuno-tolerance is both normal and essential is maternal self-suppression during pregnancy which allows two separate immunologic organisms to survive intimate relations side-by-side.
At four weeks of pregnancy, the tiny developing fetus is already developing cells that will ultimately differentiate into immune blood cells. By the third month of pregnancy, these cells are traveling through blood channels to the liver, spleen and thymus. Some of them-–B cells from bone marrow, and T-cells in the thymus – are already functional, but not needed. the womb is sterile. By 19 weeks, immune cells have also been distributed to intestinal lymph nodes.
Mothers and babies are not identical genetically. And yet the mother’s immune system spares the developing fetal cells. While housed in the sterile womb, fetal cells don’t require an active immune system of their own. Also by the fourth or fifth week of developing, the fetus has seeded the mother’s circulatory system with fetal cells, and these are tolerated and not rejected as foreign. Studies have shown that up to 0.1% of a mother’s adult cells may genetically map to her child. This is termed “microchimerism.”
As long as the child is in-utero, its immune system sleeps, and the mother tolerates her exposure to occasional fetal cells as benign and acceptable. All that changes at birth.
The newborn child is “immunogenically naive” and at risk as he/she passes through the bacterial rich vaginal canal. That is not to say the child is weapon-less. Beginning at 13 weeks, mothers antibodies have been crossing over the placenta into the fetus. By late in the 3rd trimester, these are abundant. The mother’s breast milk/colostrum is also rich in antibodies, and immunologically actives cells, granules, and enzymatic fluids. These provide immediate short-lived immune protection, and a chance to catch-up. But the supply of fast responding neutrophils is limited in this two-month process, and the newborn is vulnerable to a range of infections, most especially Streptococcus, Staphylococcus, Klebsiella , Hemophilis influenza and Meningococcus.
When the baby’s immune system kicks in (after 2 months), every pathogen is brand new. It has no memory until adaptive immunity (in the form of B and T-cell lymphocytes) generates specific immunoglobulin antibodies and receptors that can tag future invaders for destruction. This is why pediatricians instruct new parents that any fever before two months of age requires immediate examination.
It is fair to say that a great deal remains to be understood in the field of immunology. But researchers believe that further study of fetal immunity could unleash an array of new discoveries. “Tolerance to the fetal allograft” carries a great deal of academic interest for sure. But understanding the intricate chemical and physiologic systems that make this possible, many believe, could lead to clinical breakthroughs in cancer therapy, management of auto-immune disease, and avoidance 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 held theory of “self vs. non-self” from a May, 2025 publication in Frontiers in Immunology:
“Its partial obsolescence is, in fact, a tribute to how far immunology has come. As we move into 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 an ever-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 figure this all out? Maybe not.
But Anthropic CEO Dario Amodei, who used to be a biomedical researcher, switched over to AI to give humans the edge over Augustus de Morgan’s fear. As he recently said, “One of the observations that I most had when I worked in that field was the incredible complexity of it. And I had this sense of: Man, this is too complicated for humans. We’re making progress on all these problems of biology and medicine, but we’re making progress relatively slowly. So what drew me to the field of A.I. was this idea of: Could we make progress more quickly?”
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. (Grove/2020).
