Complexity in medicine: some thoughts

I have been thinking recently about medicine and complexity, as a result of several conversations over many years. In particular, the Cynefin framework developed by Dave Snowden (see diagram below) seems a useful lens to use (this thought is not original to me – see among others, the articles “The Cynefin framework: applying an understanding of complexity to medicine” by Ben Gray and “Cynefin as reference framework to facilitate insight and decision-making in complex contexts of biomedical research” by Gerd Kemperman). I will also refer to two case studies from the book Five Patients by Michael Crichton, which is still quite relevant, in spite of being written in 1969.


The Cynefin framework developed by Dave Snowden. The central dark area is that of Disorder/Confusion, where it is not clear which of the four quadrants apply (image: Dave Snowden).

The Cynefin framework divides problems into four quadrants: Obvious, Complicated, Complex, and Chaotic. In addition, the domain of Disorder/Confusion reflects problems where there is no clarity about which of the other domains apply. In medicine, this reflects cases where multiple factors are at work – potentially, multiple chronic conditions as well as one or more acute ones. These conditions can exist in all four quadrants. Ben Gray gives the example of a child with a broken arm linked to both a vitamin deficiency and an abusive home environment. Several quite different interventions may be required.

The Obvious Quadrant

The quadrant of the Obvious applies to conditions with clear cause and effect, where there is a single right answer. According to Dave Snowden, the appropriate response is to sense what is going on, categorise the situation as one on a standard list, and then to respond in the way that people have been trained to do. This response may be trivial (a band-aid, say), or it may involve enormous professional skill. In medicine, much of nursing falls in this quadrant, as does much of surgery.

Michael Crichton’s Five Patients discuses the case of Peter Luchesi, a man admitted to Massachusetts General Hospital during 1969 with a crushed arm and nearly severed hand, as the result of an industrial accident:

Three inches above the left wrist the forearm had been mashed. Bones stuck out at all angles; reddish areas of muscle with silver fascial coats were exposed in many places. The entire arm about the injury was badly swollen, but the hand was still normal size, although it looked shrunken and atrophic in comparison. The color of the hand was deep blue-gray.

Carefully, Appel picked up the hand, which flopped loosely at the wrist. He checked pulses and found none below the elbow. He touched the fingers of the hand with a pin and asked if Luchesi could feel it; results were confusing, but there appeared to be some loss of sensation. He asked if the patient could move any of his fingers; he could not.

Meanwhile, the orthopedic resident, Dr. Robert Hussey, arrived and examined the hand. He concluded that both bones in the forearm, the radius and ulna, were broken and suggested the hand be elevated; he proceeded to do this.

Outside the door to the room, one of the admitting men stopped Appel. ‘Are you going to take it, or try to keep it?’

‘Hell, we’re going to keep it,’ Appel said. ‘That’s a good hand.’

Once the surgeons had sensed the problem and categorised it as an arm reconstruction, a team of three surgeons, two nurses, and an anaesthetist (all highly trained in their respective fields) then spent more than 6 hours in the operating theatre, repairing bone, tendons, and blood vessels. Certainly not trivial, but a case of professionals doing what they were trained to do.

The Complicated Quadrant


Public Domain image

The Complicated quadrant is the realm of diagnosis. Information is collected – in medicine, that generally means patient history, blood tests, scans, etc. – and is then subjected to analysis. This identifies the nature of the problem (in an ideal world, at least), which in turn indicates the appropriate response.

Diagnosis by physicians typically searches for the cause of an illness, while diagnosis by nurses typically focuses on severity. This reflects differences in the responses that physicians and nurses have been trained to provide (the triage officer in a modern hospital is typically a nurse).

Decades of work have gone into automating the diagnosis process – initially using statistical analysis, later using expert systems, and most recently using machine learning. At present, the tool of choice is still the human brain.

In general, modern medicine excels when it operates in the Obvious and Complicated quadrants.

The Complex Quadrant

The Complex quadrant is the realm of interactions. It is inherently very difficult to deal with, and cause and effect are difficult to disentangle. The paradigm of information collection and analysis fails, because each probe of the system changes it in some way. The best approach is a sequence of experiments, following each probe with a response that seems reasonable, and hoping to find an underlying pattern or a treatment that works. Michael Crichton provides this example:

Until his admission, John O’Connor, a fifty-year-old railroad dispatcher from Charlestown, was in perfect health. He had never been sick a day in his life.

On the morning of his admission, he awoke early, complaining of vague abdominal pain. He vomited once, bringing up clear material, and had some diarrhea. He went to see his family doctor, who said that he had no fever and his white cell count was normal. He told Mr. O’Connor that it was probably gastroenteritis, and advised him to rest and take paregoric to settle his stomach.

In the afternoon, Mr. O’Connor began to feel warm. He then had two shaking chills. His wife suggested he call his doctor once again, but when Mr. O’Connor went to the phone, he collapsed. At 5 p.m. his wife brought him to the MGH emergency ward, where he was noted to have a temperature of 108 °F [42 °C] and a white count of 37,000 (normal count: 5,000–10,000).

The patient was wildly delirious; it required ten people to hold him down as he thrashed about. He spoke only nonsense words and groans, and did not respond to his name. …

One difficulty here was that John O’Connor could not speak, and so could not provide information about where he felt pain. He appeared to suffer from septicaemia (blood poisoning) due to a bacterial infection in his gall bladder, urinary tract, GI tract, pericardium, lungs, or some other organ. Antibiotics were given almost immediately, to save his life. These eliminated the bacteria from his blood, but did not tackle the root infection. They also made it difficult to identify the bacteria involved, or to locate the root infection, thus hampering any kind of targeted response. In the end (after 30 days in hospital!) John O’Connor was cured, but the hospital never did locate the original root infection.

Similar problems occur with infants (Michael Crichton notes that “Classically, the fever of unknown origin is a pediatric problem, and classically it is a problem for the same reasons it was a problem with Mr. O’Connor—the patient cannot tell you how he feels or what hurts”). As Kemperman notes, medical treatment of the elderly often also falls in the Complex domain, with multiple interacting chronic conditions, and multiple interacting drug treatments. Medical treatment of mental illness is also Complex, as the brain adapts to one treatment regimen, and the doctor must experiment to find another that stabilises the patient.

Similarly Complex is the day-to-day maintenance of wellness (see the Food and Wellness section below) which often falls outside of mainstream medicine.

The Chaotic Quadrant

The Chaotic quadrant is even more difficult than the Complex one. Things are changing so rapidly that information collection and experimentation are impossible. The only possible response is a dance of acting and reacting, attempting to stabilise the situation enough that it moves from Chaotic to Complex. Emergency medicine generally falls in this quadrant – immediate responses are necessary to stop the patient dying. In the airline industry, the ultimate (and extremely rare) nightmare of total engine failure shortly after takeoff (as in US Airways Flight 1549) sits here too – each second of delay sees gravity take its toll.

Success in the Chaotic domain requires considerable experience. In cases where the problem is a rare one, this experience must be created synthetically using simulation-based training.

Food and Wellness

Michael Crichton notes that “The hospital is oriented toward curative treatment of established disease at an advanced or critical stage. Increasingly, the hospital population tends to consist of patients with more and more acute illnesses, until even cancer must accept a somewhat secondary position.” There is, however, a need for managing the Complex space of minor variations from wellness, using low-impact forms of treatment, such as variations in diet. Some sections of this field are reasonably well understood, including:

Traditional culture often addresses this space as well. For example, Chinese culture classifies foods as Yin (cooling) or Yang (heaty) – although there is little formal evidence on the validity of this classification.

There remain many unknowns, however, and responses to food are highly individual anyway. There may be a place here for electronic apps that record daily food intake, medicine doses, activities, etc., along with a subjective wellness rating. Time series analysis may be able to find patterns in such data – for example, I might have an increased chance of a migraine two days after eating fish. Once identified, such patterns suggest obvious changes in one’s diet or daily schedule. Other techniques for managing this Complex healthcare space are also urgently needed.


Looking back: 2009


Washington, DC in June 2009

In 2009, I had the privilege of visiting the United States twice (in June and November).

This was the year that saw the launch of the Lunar Reconnaissance Orbiter (which imaged, among other things, the Apollo 11 landing site), the Kepler space telescope (designed to look for exoplanets), the Herschel space observatory (an infrared telescope studying star formation), the Planck spaceprobe (which studied the cosmic microwave background), and the Wide-field Infrared Survey Explorer (an infrared telescope looking for minor planets and star clusters).


Apollo 11 landing site, imaged by the LRO (with photographs from 1969 inset)

More metaphorically, Bitcoin and the programming language Go were also launched. US Airways Flight 1549, on the other hand, was skillfully landed in a river. In archaeology, hoards were discovered in Staffordshire (gold and silver metalwork) and Shrewsbury (Roman coins). Australian Hospital Ship Centaur, torpedoed in 1943, was discovered off the Queensland coast.

Books of 2009 included Wolf Hall by Hilary Mantel (set in 1500–1535; a TV series of 2015), The Windup Girl by Paolo Bacigalupi (dystopian science fiction; Nebula Award winner), and The Maze Runner by James Dashner (young adult dystopian sci-fi; a film of 2014). Books that I later reviewed include The Lassa Ward by Ross Donaldson and God’s Philosophers by James Hannam.

Movies of 2009 included Avatar (rather disappointing), 2012 (a little silly), Angels & Demons (a travesty), Up (Pixar/Disney), Coraline (designed to give children nightmares), District 9 (designed to give adults nightmares), Julie & Julia (a film about cooking), The Imaginarium of Doctor Parnassus (a film about mirrors), and Sherlock Holmes (a lot of fun). On the whole, a good year for films.

In this series: 1978, 1980, 1982, 1984, 1989, 1991, 1994, 2000, 2004, 2006, 2009.


Recreational mathematics


The wolf, the goat, and the cabbages

Dancing alongside the more serious practitioners of mainstream mathematics are the purveyors of mathematical puzzles and problems. These go back at least as far as Diophantus (c. 200–284), the Alexandrian “father of algebra.” Alcuin of York (c. 735–804) produced a collection of problems that included the the wolf, the goat, and the cabbages (above); the three men who need to cross a river with their sisters; and problems similar to the bird puzzle published by Fibonacci a few centuries later. In more modern times, Martin Gardner (1914–2010) has done more than anyone else to popularise this offshoot of mathematics. It is often called “recreational mathematics,” because people do it for fun (in part because they are not told that it is mathematics).

Particularly popular in recent times have been Sudoku (which is really a network colouring problem in disguise) and the Rubik’s Cube (which illustrates many concepts of group theory, although it was not invented with that in mind). Sudoku puzzles have been printed in more than 600 newspapers worldwide, and more than 20 million copies of Sudoku books have been sold. The Rubik’s Cube has been even more popular: more than 350 million have been sold.


A Soma cube, assembled

Recreational puzzles may be based on networks, as in Hashi (“Bridges”). They may be based on fitting two-dimensional or three-dimensional shapes together, as in pentominoes or the Soma cube. They may be based on transformations, as in the Rubik’s Cube. They may even be based on arithmetic, as in Fibonacci’s problem of the birds, or the various barrel problems, which go back at least as far as the Middle Ages.

In one barrel problem, two men acquire an 8-gallon barrel of wine, which they wish to divide exactly in half. They have an empty 5-gallon barrel and an empty 3-gallon barrel to assist with this. How can this be done? It is impossible to accurately gauge how much wine is inside a barrel, so that all that the men can do is pour wine from one barrel to another, stopping when one barrel is empty, or the other is full [highlight to show solution → (8, 0, 0) → (3, 5, 0) → (3, 2, 3) → (6, 2, 0) → (6, 0, 2) → (1, 5, 2) → (1, 4, 3) → (4, 4, 0)]. There is a similar problem where the barrel sizes are 10, 7, and 3.


The barrels

Apart from being fun, puzzles of this kind have an educational benefit, training people to think. For this reason, Alcuin called his collection of problems Propositiones ad Acuendos Juvenes (Problems to Sharpen the Young). Problems like these may also benefit the elderly – the Alzheimer’s Association in the United States suggests that they may slow the onset of dementia. This is plausible, in that thinking hard boosts blood flow to the brain, and research supports the idea (playing board games and playing musical instruments are even better).


Looking back: 2004

In 2004, I was privileged to visit Middle Earth (aka New Zealand) with a colleague and to present the paper “Network Robustness and Graph Topology.” A major event of that year was the landing of the Mars rovers Spirit and Opportunity. Intended to operate for 90 Martian days (92 Earth days), Spirit kept going until 2010 (as xkcd remarked on in the comic above) and Opportunity set a record by operating until 2018. Also in 2004, the Stardust spaceprobe collected some comet dust.

On a more sombre note, 2004 saw the Boxing Day Tsunami. In the field of technology, Facebook and Gmail both launched in 2004, and Vint Cerf and Bob Kahn shared the Turing Award (for having invented the Internet).

This was an excellent year for cinema. Examples from different genres include National Treasure, Troy, Van Helsing, Man on Fire, Hotel Rwanda, The Village, Howl’s Moving Castle, and The Passion of the Christ. I certainly have memories that I treasure.

In this series: 1978, 1980, 1982, 1984, 1989, 1991, 1994, 2000, 2004, 2006.


Looking back: 2006


Oxford, 2006

In 2006, I had the privilege of attending two conferences in England (the 11th International Command & Control Research & Technology Symposium in Cambridge and the Complex Adaptive Systems and Interacting Agents Workshop in Oxford).

This was the year that NASA launched the New Horizons spaceprobe towards Pluto (it was to arrive in 2015). Ironically, later in 2006, the International Astronomical Union somewhat controversially downgraded the status of Pluto to that of a “dwarf planet.”

Grigori Perelman’s proof of the Poincaré conjecture was declared the “Breakthrough of the Year” by the journal Science. A variety of books, such as this one, have tried to explain what the conjecture (now theorem) is about. So far, this is the only one of the seven Millennium Prize Problems to be solved.

Perelman was offered, but refused, the prestigious Fields Medal (in interviews, he raised some ethical concerns regarding the mathematical community).

Books of 2006 included the intriguing World War Z (later made into a mediocre film). Movies included Pan’s Labyrinth, Children of Men, Apocalypto, Black Book, Pirates of the Caribbean II, Cars, and The Nativity Story.

And in music, Carrie Underwood took the world by storm, singing about Jesus and about smashing up motor vehicles with baseball bats.


Personality and Gender

The so-called “Big Five” personality traits are often misunderstood. They all have catchy names, expressed by the acronym CANOE (or OCEAN), but in fact all they are is a summary of answers to certain kinds of personality questions:

  • Conscientiousness: I pay attention to details; I follow a schedule; …
  • Agreeableness: I am interested in people; I feel the emotions of others; …
  • Neuroticism: I get upset easily; I worry about things; …
  • Openness to experience: I am full of ideas; I am interested in abstractions; …
  • Extraversion: I am the life of the party; I start conversations; … (this last one is also measured by the MBTI test)

These tests work in multiple cultures. In this article, I am using data from the Dutch version of the test, the “Vijf PersoonlijkheidsFactoren Test” developed by Elshout and Akkerman. Specifically, I am using data from 8,954 psychology freshmen at the University of Amsterdam during 1982–2007 (Smits, I.A.M., Dolan, C.V., Vorst, H.C., Wicherts, J.M. and Timmerman, M.E., 2013. Data from ‘Cohort Differences in Big Five Personality Factors Over a Period of 25 Years’. Journal of Open Psychology Data, 1(1), p.e2). In my analysis, I have compensated for missing data and for the fact that the sample was 69% female.

The Dutch test consists of 70 items, in 5 groups of 14. The following tree diagram (click to zoom) is the result of UPGMA hierarchical clustering on pairwise correlations between all 70 items. It can be seen that they naturally cluster into 5 groups corresponding almost perfectly to the “Big Five” personality traits – the exception being item A11, which fits extraversion slightly better (r = 0.420) than its own cluster of agreeableness (r = 0.406). This lends support to the idea that the test is measuring five independent things, and that these five things are real.

On tests like this, women consistently score, on average, a little higher than men in conscientiousness, agreeableness, neuroticism, and extraversion (and in this dataset, on average, a little lower in openness to experience). Mean values for conscientiousness in this dataset (on a scale of 14 to 98) were 60.3 for women and 56.1 for men (a difference of 4.2). For agreeableness, they were 70.6 for women and 67.6 for men (a difference of 3.0). There are also small age effects for conscientiousness, agreeableness, and openness to experience (over the 18–25 age range), which I have ignored.

The chart below (click to zoom) shows distributions of conscientiousness and agreeableness among men and women, and the relative frequency of different score ranges (compensating for the fact that the sample was 69% female). Thus, based on this data, a random sample of people with both scores in the range 81 to 90 would be 74% female. With both scores in the range 41 to 50, the sample would be 72% male. This reflects a simple mathematical truth – small differences in group means can produce substantial differences at the tails of the distribution.


The modern Trivium and the teaching of science

The “trivium” approach to education derives from “The Lost Tools of Learning,” a 1947 speech by scholar and detective story author Dorothy L. Sayers. This approach takes the seven liberal arts (illustrated above), drops the all-important quadrivium, and applies the remainder in a largely metaphorical way. It is an interesting approach, although it inevitably under-emphasises mathematics. The door to Plato’s Academy was marked “Let no one ignorant of geometry enter (Ἀγεωμέτρητος μηδεὶς εἰσίτω),” and this referred to the most advanced mathematic of his day. I’m not sure that the “trivium” approach to education delivers that level of mathematical knowledge. Then again, does the standard approach?

ΑΓΕΩΜΕΤΡΗΤΟΣ ΜΗΔΕΙΣ ΕΙΣΙΤΩ

Science, on the other hand, can be fitted quite well into the “trivium” model. The three stages of this model (largely metaphorical, as noted) are “grammar,” “logic,” and “rhetoric.”

The “grammar” stage (intended for ages 6 to 10 or so) covers basic facts. Science at this level logically includes what used to be called natural history – the close observation of the natural world. Maintaining a nature journal is an important part of this, as are simple experiments, the use of a telescope, collections of objects (rocks, shells, etc.), and simple measurements (such as recording measurements from a home weather station).



Mother and child nature journaling examples from Nature Study Australia Instagram and website

Dorothy L. Sayers has nothing to say about science in the “logic” stage (apart from fitting algebra and geometry here), but the “logic” stage would reasonably include taxonomies, empirical laws, and an exploration of how and why things work the way they do – that is, the internal logic connecting scientific observations and measurements. A degree of integration with history education would provide some context regarding where these taxonomies and laws came from, and why they were seen as important when they were formulated.


Exploring Boyle’s law with a simple apparatus

In the “rhetoric” stage, the “how” and “why” of science would be explored in more detail, along with practical applications and project work (such as entering a science competition, or possibly even collaborating with local academics on a scientific conference paper).


A US Army engineer helps judge high school science projects (photo: Michael J. Nevins / US Army)

I suspect that quite a decent science education programme could be worked out on such a basis. If any reader knows of it having been done, please add a comment.