Abstract
Even if the world were only complicated, it would still defy human comprehension. It is far too immense. We need methods to aid in our apprehension of the world in its entirety. Fortunately, the world seems to be organized in a way that allows us to see it in levels that vary in scale and composition, organized in a hierarchical fashion. The concept of levels has a long history going back to Aristotle who ordered living things based on the biological functions of the soul. A hierarchy provides a structured way of thinking across scale and identifying shared aspects of structures, processes or patterns of behavior. Hierarchical living systems can be described as being built from components that are individually “simple” and that interact with each other in relatively “simple” ways; yet at another level of analysis these systems exhibit some “complex” overall behavior that is not readily predictable from the subunits themselves. The importance of higher levels of the living systems hierarchy has become clearer and it becomes a legitimate question to ask what (and not who) gets diabetes, e.g., the genes? The beta cells? The individual? The family? Friends? Community? Society? Each level constitutes a context for the next lower level and a yes answer has major implications for how interventions should be designed.
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Notes
- 1.
I have no idea how I had never heard about Murray Bookchin until writing this book, but somehow I missed him. He warned about pesticides before Rachel Carson’s book Silent Spring of 1962. Given the politics of the time while I was in college – late 1960s – and the politics of my parents and friends, I would have expected to have heard of him. But better late than not at all. There is a biography: Janet Biehl Ecology or Catastrophe: The Life of Murray Bookchin. Oxford University Press (2015)
- 2.
This “workaround” obviously violated policy but workarounds have a long history is maintaining operations. In fact, as any union shop steward can tell you, the way to bring an organization to its knees is to follow policy to the letter. My little bit of rebellion paled in comparison to the actions of one of my first supervisors. He had been recruited to the medical center with a promise to renovate laboratory space by the time he arrived. When his did come several months later, nothing had been done. He went up the chain, but nothing happened. Appeals having failed, he took a sledgehammer to one of the walls that had been slated for removal. I don’t think that made him many friends.
- 3.
My plan for my time as a visiting fellow/scholar at University of Cambridge was to write a book on the philosophy of complexity. However, my trajectory changed. First, I decided that I wasn’t smart enough to do philosophy, at least as the dons did. In our medicine and philosophy reading group I found that I would get bogged down in philosophical terminology and then lose the flow of the argument. It was interesting discussion but in the end there was something missing, something unsatisfying about it. I felt ineluctably drawn to my own experience as a physician rather than the more refined heights of rhetoric. That meant that if I were to write a book, it would have to emphasize my experience and offer practical benefit to readers.
- 4.
Hence, Three Rivers Stadium in Pittsburgh.
- 5.
Physicalists would argue that someday we will be able to predict that behavior.
- 6.
In Noble’s extremely provocative book is a combination of biology and philosophy in which he proposes the concept of biological relativity that living organisms operate at multiple levels of complexity and no level is privileged, i.e., there is both downward as well as upward causation (questioning the central dogma). Consequently, he suggests, biological organisms must be analyzed from a multi-scale, relativistic perspective. To say that he is a controversial figure is an understatement. I came across his book shortly after I arrived in the UK and was browsing in the Cambridge University Bookstore. It was the first book I bought there.
- 7.
History of diabetes – The first mentions of what might be diabetes date back to sixteenth century BCE Egypt when Hesy-Ra, a physician, documented frequent urination as a symptom of a disease that also caused emaciation. At about the same time, physicians in India noted a similar condition and that ants were attracted to the urine of affected patients. The disease was given its name “diabetes” by Apollonius of Memphis in 250 BCE from the Greek διαβητης (which signifies a siphon) because the fluid does not remain in the body, but uses the man’s body as a ladder (διαβαθρη) whereby to leave it. (https://www.diapedia.org/introduction-to-diabetes-mellitus/1104692125/aretaeus-of-cappadocia) The first extensive description came about 350–400 years later when Arateus of Cappadocia, another Greek physician) wrote:
Diabetes is a wonderful affliction, not very frequent among men, being a melting down of the flesh and limbs into urine. Its cause is of a cold and humid nature, as in dropsy. The course is the common one, namely, the kidneys and bladder; for the patients never stop making water, but the flow is incessant, as if from the opening of aqueducts. The nature of the disease, then, is chronic, and it takes a long period to form; but the patient is short-lived if the constitution of the disease be completely established; for the melting is rapid, the death speedy. Moreover, life is disgusting and painful; thirst, unquenchable; excessive drinking, which, however, is disproportionate to the large quantity of urine, for more urine is passed; and one cannot stop them either from drinking or making water. Or if for a time they abstain from drinking, their mouth becomes parched and their body dry; the viscera seem as if scorched up; they are affected with nausea, restlessness, and a burning thirst; and at not distant term they expire. D. Lynn Loriaux. Aretaeus of Cappadocia (First and Second Centuries C.E.)in A Biographical History of Endocrinology, First Edition. © 2016 John Wiley & Sons, Ltd. Published 2016 by John Wiley & Sons, Ltd. Chap. 7 citing The Extant Works of Aretaeus, the Cappadocian. Special Edition. Birmingham, AL: Gryphon Editions, 1990.
Parenthetically, I have never understood the phrase wonderful affliction since I have yet to meet anyone with diabetes who thought it was wonderful. Perhaps, the phrase is analogous to the way unusual diseases are considered interesting today, though God help those who have an “interesting” condition. Much better to have something boring and routine where treatment is straightforward.
Galen, another Greek physician whose work set the course for medicine in the West for the next 1500 (and in many ways held it back) felt that diabetes was a disease of the kidneys. Interestingly, similar observations were being made on the other side of the world – in China. Chang Chung Ching, the Chinese Hippocrates described the symptoms of polyphagia, polydipsia and polyuria. Perhaps even more interesting is that by the seventh century CE, Chinese physicians had described three types of diabetes: 1- intense thirst, copious dringkin, excretion of large amounts of urine that is sweet; 2- patients eat a great amount; little thirst, urine less in quantity though frequently passed, has fatty appearance; and 3- thirst but can’t drink much, edema of the legs, wasting of the feet, impotence. Although the third sound more like nephrotic syndrome, the first two could plausibly represent types 1 and 2 diabetes. See: Medvei VC. The history of clinical endocrinology: a comprehensive account of endocrinology from earliest times to the present day. CRC Press; 1993 Jan 15.
At some point and probably many different points, it became clear that in this condition the urine was sweet and generations of tasters made the diagnosis. This form of diabetes became known as diabetes mellitus or honey (sweet) urine in contrast to diabetes insipidus with non-sweet or flat tasting urine due to deficiency of a posterior pituitary hormone (anti-diuretic hormone of vasopressin). Major advances in understanding came in the 19th and early 20th centuries. Paul Langerhans, a German medical student wrote is MD thesis in 1869 describing islets of cells that were different from the rest of the pancreas. He didn’t propose any function and was actually quite apologetic about his thesis, hoping that his meager efforts would be sufficient to get a degree. In 1893 Gustave-Edouard Laguesse suspected that the islets had an endocrine function. and named them for Langerhans, alas 5 years after Langerhans had died. Although the first hormone was discovered in 1902 by Bayliss and Starling – secretin and the term hormone (from I will arouse) was coined by Bayliss in 1905, the idea of glands producing something had been shown, especially in relation to the thyroid. In 1891–2, George Murray treated a patient with severe hypothyroidism (myxedema) using thyroid obtained from sheep and completely reversing the condition. The recommendation by Chinese physician Wang Hei in 1475 CE to treat goiter with minced thyroid had not been picked up in the West. https://www.thyroid.org/about-american-thyroid-association/clark-t-sawin-history-resource-center/thyroid-history-timeline/
Rapid progress in diabetes was made as it was demonstrated that removing the pancreas from a dog rendered the animal diabetic leading to the classic studies of Banting and Best in discovering insulin. This exciting story is recounted by Michael Bliss in The Discovery of Insulin, though of course, the story is far more complicated than the few lines I have devoted to it. Chapter 1 recounts how the medical model of type 1 diabetes sufficed until the appearance of the more common type 2 diabetes. (Bliss M. The discovery of insulin. University of Chicago Press; 2013 Feb 15) However, the medical model forms the core of the explanation for the etiology of disease as it continues to be taught in medical school.
- 8.
The term was introduced in 1900 by Paul Erlich. The term silver bullet continues to be used today.
https://invisiverse.wonderhowto.com/news/new-approach-could-be-silver-bullet-against-antibiotic-resistant-e-coli-other-gram-negative-bacteria-0177599/. Accessed 19 April 2018.
- 9.
More recent models of disease include multiple cause-single disease, e.g., heart disease; one cause, multiple diseases, e.g., tobacco and lung cancer, empysema, heart disease, and other conditions; multiple causes, multiple diseases, and others.
- 10.
For a wonderful explication of a complex systems approach to obesity see: Foresight. Tackling Obesities: Future Choices – Project Report 2nd Edition. Government Office for Science, 2007. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/287937/07-1184x-tackling-obesities-future-choices-report.pdf
- 11.
One of my most useful abilities is in connecting people, particularly people with different but relevant and potentially overlapping interests (i.e., weak ties). This is particularly true in research. I was once at a VA HSR&D strategic planning meeting with about 75 others. We were seated in tables of eight in no particular order. I knew most of the people at my table, but not everyone. One member of the group stood up and said that it would be good for everyone to introduce themselves. She pointed to the first who said a few words, then the second and third and then got to me and said: “everyone knows dave” and moved on to the next person before I could utter a word. It was ironic that before she introduced herself I had no idea who she was.
- 12.
The story of the Castle Bravo test of the first hydrogen bomb (fusion bomb) involves a series of tragedies. See: Bombing the Marshall Islands-A Cold War Tragedy by Keith M. Parsons and Robert A. Zaballa. Cambridge University Press, 2017.
We continue to use the Kwajalein Atoll, the largest in the world (about 150 miles across) as the target for testing intercontinental ballistic missiles. While there, my friends and I were encouraged to go the beach on the north end of the island at 5 AM the next day – wink wink, nod nod. We set the alarm and off we went to the beach. We were alone with the most incredible starry sky I had ever seen – more than 1000 miles from any pollution and there wasn’t much light pollution either. We sat enjoying the view and then about 30 minutes later a whole bunch of people arrived with beach chairs. It was still quite dark, but apparently, the call went out that the missile had been launched and would arrive about 20 minutes later. We saw a light that split into seven plumes of different colored smoke – 7 warheads. The word awe hardly begins to approach the feeling.
- 13.
http://diabetes.diabetesjournals.org/content/diabetes/45/9/1282.full.pdf
I can’t resist telling an anecdote about Dr. Forsham. During my fellowship, my father in New York became very ill and it wasn’t clear whether he would survive. I told Dr. Forsham that I had to go back to New York. He called his secretary in and said: “Kathy, make flight reservations for Dave and put it on my card.” That was that. He didn’t ask to be paid back (though I did). He just did a good deed for one of his students. I have never forgotten his kindness and have tried to pay it forward.
- 14.
The sentiment that bologna or boloney no matter how thinly sliced is still bologna has been attributed to the early twentieth century politician Al Smith though there is some debate: http://listserv.linguistlist.org/pipermail/ads-l/2010-August/101744.html
- 15.
Saul J. Wiener, a friend and colleague has done seminal work in the area of contextual errors – describing them, demonstrating their frequency in practice, and in a wonderful book entitled “Listening to What Matters” written with Alan Schwartz innovative methods to address them.
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Aron, D.C. (2020). Levels and Hierarchy in Complex Systems: What Gets Diabetes?. In: Complex Systems in Medicine. Springer, Cham. https://doi.org/10.1007/978-3-030-24593-1_5
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