I read a story yesterday in The Atlantic about how COVID-19 interacts with our immune systems. It opened with some humor about the complexity of our immune systems, and used that as a refrain throughout the article, but it nevertheless attempted to explain how the immune system works as if it were well understood! I want to explore why I think that - despite our immense knowledge - our physiology is not well understood. In fact I want to suggest that the rapid pace at which we are accumulating knowledge of biology is evidence, instead, of how much more we have to learn. And I want to make some observations about what this should mean for K-12 teaching of biology, where I have some experience.
Let’s take a minute to think about T-cells. My first memory of even hearing the phrase “T-cell” was in 1981 when AIDS was first being described and discussed. Articles in popular magazines like Discover and Science 80 called the new disease T-lymphotrophic virus and they were supplemented with imaginative descriptions of the human immune system. In communities where AIDS was a concern (as opposed to a hysterical panic) there was a lot of discussion about T-cell counts. But how old was knowledge of those T-cells? Not very.
The “T” stands for their source in the thymus, a small organ in front of your heart, and it is intended to distinguish them from B-cells, also small lymph cells, but arising instead in bone marrow. Less than thirty years earlier, the great Johns Hopkins pathologist Arnold Rice Rich (father of poet Adrienne Rich) who wrote the book on TB (really, Pathogenesis of Tuberculosis, 1000 pages) said “literally nothing of importance is known” of small lymphocytes and added that this was “one of the most humiliating and disgraceful gaps in all medical knowledge. By 1964, scientists had figured out that those lymphocytes had something to do with an immune system but hadn’t differentiated them into the many types students are now required to memorize with the aid of flash cards. They hadn’t yet divided them into B and T. In fact, they actually thought the thymus was a vestigial organ. As late as 1971, just ten years before I started hearing popular disquisitions on T-cells, medical dictionaries were still saying that the function of the thymus was “obscure.” That is definitely what I was taught when I took high school biology in 1967.
The Australian physician and scientist Jacques F.A.P. Miller spent the 60’s discovering its function, but his work had difficulty gaining acceptance. His politest critics merely accused him of “complicating things.” In 1968 when he presented evidence that T (thymus-originating) and B (bone-marrow-originating) were two kinds of lymph cells he was publicly reminded, in front of a auditorium full of immunologists) that B and T were the first and last letters of the word bullshit. By the 1980’s the receptors by which B-cells recognized foreign cells were mostly understood. Only in the 2000’s were T-cell receptors understood. Moreover, T-cells were broken down into distinctive subtypes: Cytotoxic, Killer, Helper, Memory, Regulatory, Gamma Delta, and Mucosal. (More memorization, more flash cards) This January, researchers in Wales happily publicized their discovery of a new type of Killer T-cell!
Before stepping back to reflect on the larger significance of this minutiae - the forest in which these leaf aphids reside - let’s think a little more about their discovery, naming, and classification. B- and T-cells are lymphocytes, two of at least three kinds of cells found in lymph, a fluid that circulates through the body in separate system from blood. Lymphocytes are one of at least five types of leukocytes, or white blood cells. While red cells (then called “corpuscles”) were noticed with fascination by the first microscopists in the 17th century when they turned their lenses on blood (Anton von Leeuwenhoek produced the first drawings in 1695) it wasn’t until a century later that a British surgeon noticed small transparent cells among the larger red ones. He accurately guessed that they came from the lymph system. Their appearance was described in 1843, but it wasn’t until the 1870’s that new staining techniques allowed scientists to see their structure. That work was done by Paul Ehrlich, who won the 1908 Nobel Prize in Medicine. It still didn’t allow anyone to know their function, or how they performed that function, or how very many kinds there were. The color “white” refers not to the cells themselves but to how they appear overall when blood is allowed to separate into different layers, whether through settling or centrifuging.
What does all this mean? For me a couple of observations emerge. One is the redundancy of biological systems. I reread the material above and note, for example, the existence of NK (Natural Killer) Cells, NKT (Natural Killer T) cells, and Cytotoxic T cells: different varieties of lymphocytes with similar abilities to destroy other cells. But these aren’t completely distinct categories, they overlap in their mechanisms and origins. I think that makes their redundancies different than redundancies created by engineers, such as fail-safe mechanisms or, say, drop-down menus coexisting with keyboard shortcuts. I will boldly say that immune mechanisms in particular have to evolve rapidly to keep up with rapidly-evolving viruses and that every single element of what we understand to be a system is under selective pressures. And the results of that evolution aren’t always good as we see with autoimmune and inflammatory diseases in which one or another component of the immune system attacks our bodies and makes us sick instead of healthy. So treating this as if we can somehow “understand how it works” may not be a good intellectual model. Thinking of it as an ecosystem - all elements interacting with all other elements - may be a better model. I will return to this idea later.
Second, look at how resistant people were to recognizing the existence of T-cells. Look at how resistant they were to the idea that their ignorance about the function of the thymus didn’t mean it was vestigial! That resistance to new fact is especially notable when compared to how quick they are to add new classes of T-cells now that their existence is recognized. As a teacher, it is another reminder of how shallow the practice of memorizing all these names is by contrast with learning something about how these discoveries were made instead of pretending that lots of facts equals understanding.
Third, the rapid pace of new knowledge about this field suggests that we still have a lot to learn. If we were anywhere near a complete understanding of immunology, the pace of discovery would have slowed considerably. And the absolute astonishment about how COVID-19 works should humble everybody.
I want to write more about this, especially about biochemistry, the nervous system, and our microbial biota, but I will save all that for another day.
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